What ARE Turmeric and Curcumin?
Turmeric is a spice obtained from the dried root rhizomes of Curcuma longa, a medicinal plant from the ginger family of herbs, the Zingiberaceae. The rhizomes are dried and crushed in order to produce a yellow-orange powder. The biologically active compound within this powder is curcumin, one of the most studied phytochemicals in science. Turmeric powder contains 2% to 8% curcumin, which we isolate to 95% for medical research and nutritional supplementation.

 

What are the health properties of Curcumin?
 
"Over 10,000 research papers and over 1000 review articles have been published to discuss the molecular basis of curcumin’s attributed antioxidant, anti-inflammatory, antibacterial, antiapoptosis, anticancer, and antiaging activities." - Stem Cells Translational Medicine | 2024

"Regardless of health status, adding curcumin to one’s diet lowers circulating levels of pro-inflammatory bio-markers and raises levels of anti-inflammatory mediators. Extensive investigations have explored the beneficial effects of curcumin in numerous cancer types, encompassing breast cancer, lung cancer, cancers affecting the digestive system, as well as hematological cancers. In addition to its therapeutic attributes, curcumin has been proposed as a prospective agent in cancer prevention, primarily attributed to its antioxidant and immunomodulatory properties. Curcumin has also demonstrated its potential as an agent in the regulation of obesity and metabolic processes. In addition, curcumin aids in the management of metabolic syndrome and hyperlipidemia and has shown promise as a robust endocrine system modulator, boosting or controlling the release of several hormones, including insulin. Curcumin has also exhibited beneficial effects in various pulmonary disorders, highlighting its potential in the management of respiratory system-related conditions. Curcumin also exhibits the capacity to attenuate the natural response of the body to cutaneous wounds, including inflammation and oxidation. Findings from a meta-analysis study on human subjects affected by depression have also revealed that curcumin might improve depressive and anxiety symptoms in these individuals,suggesting that it can be utilized as an adjunct treatment for depressive disorders. The clinical utility of curcumin extends to the realm of neurodegenerative diseases; dementia, Alzheimer’s disease and Parkinson's disease. Due to its free radical scavenging, mitochondrial protecting, anti-inflammatory, and iron-chelating properties, curcumin is regarded as a promising therapeutic and nutraceutical agent for the treatment of Parkinson's disease. Accordingly, several studies have indicated that curcumin prevents the dopaminergic neuronal loss in models of Parkinson's disease, which provides further evidence for a potential neuroprotective role for curcumin in Parkinson's disease." - Heliyon | 2024

"Studies on curcumin have since confirmed its powerful antioxidant properties, preventing both the formation of free radicals and their neutralization, having anti-inflammatory, antibacterial, immunological, and neuroprotective properties, as well as being a regulator of the intestinal microbiota with beneficial effects on the clinical manifestations of metabolic syndrome." - Antioxidants | 2024

"Curcumin, the most abundant curcuminoid in turmeric, has been widely investigated for its various biological activities, including anti-inflammatory, antioxidant, and anticancer effects. Numerous in vitro and in vivo studies have demonstrated the ability of curcumin to modulate multiple signaling pathways involved in carcinogenesis, leading to inhibition of cancer cell proliferation, induction of apoptosis, and suppression of metastasis. Furthermore, curcumin has shown promising potential as a radioprotective agent by mitigating radiation-induced oxidative stress and DNA damage. Additionally, turmeric extracts containing curcuminoids have been reported to exhibit potent antioxidant activity, scavenging free radicals and protecting cells from oxidative damage. The multifaceted pharmacological properties of turmeric make it a promising candidate for the development of novel therapeutic strategies for cancer prevention and treatment, as well as for the management of oxidative stress-related disorders." - Frontiers in Nutrition | 2024

"Due to its variety of biological effects and implications in different diseases, curcumin has been described as “pharmacodynamically fierce". Curcumin has been found to possess a variety of biological properties, including its immunomodulatory, anti-inflammatory, antioxidant, neuroprotective, and anti-cancer effects. In addition, curcumin has been studied in different diseases, such as Alzheimer’s disease, pancreatitis, psoriasis, arthritis, cardiovascular diseases, and cancer. Curcumin has been reported to possess both preventive and therapeutic effects on several types of cancer, such as breast and prostate cancer, lung cancer, pancreatic malignancies, and brain tumors, including glioblastoma.The anti-cancer properties of curcumin have been attributed to its diverse interactions with key molecular pathways implicated in different biological processes, such as proliferation, control of the cell cycle, apoptosis, metastasis, angiogenesis, and inflammation. Moreover, curcumin has been found to specifically target cancer stem cells, a population of cells largely responsible for the resistance to established chemotherapeutic treatments and recurrence of cancer patients. Furthermore, several studies have shown that curcumin may sensitize tumor cells to both chemo- and radiotherapy and, thus, improve treatment efficacy while reducing side effects when given as an adjuvant therapy. As more clinical evidence becomes available, curcumin is likely to become a fundamental part of cancer therapies in the future." - The Role of Curcumin in Cancer | 2024

"Curcumin taken orally has been found to counteract cell damage from the environment and disease." - Prevention | 2024

"Curcumin, derived from turmeric, has long captivated the pharmaceutical field globally due to its pharmacological effects and clinical development (Hasanzadeh et al., 2020). Curcumin is a lipophilic polyphenol that is antioxidant, anti-inflammatory, and anti-fibrotic. It has been extensively used as a food seasoning because of its high level of safety (Bavarsad et al., 2019) (Figure 1). Numerous human clinical trials have extensively employed curcumin for interventions in various diseases, such as multiple myeloma, pancreatic cancer, NAFLD, colon cancer, and Alzheimer’s disease, both in vitro and in animal models (Hatcher et al., 2008)." - Frontiers in Pharmacology | 2024

"In the last ten years, there has been an increase in interest in curcumin-based therapies for the prevention and treatment of various illnesses, such as cardiovascular diseases, cancers, neurodegenerative diseases (Parkinson's, Alzheimer's and multiple sclerosis), autoimmune diseases (osteoarthritis and rheumatoid arthritis), diabetes, pulmonary diseases and some gastrointestinal disorders. Curcumin has been shown to have a positive impact on several inflammatory disorders, including diabetes and cardiovascular conditions. According to the available published literature, it can be concluded that curcumin, as a promising nutraceutical-based treatment not only has anti-inflammatory, antioxidant, and anti-apoptotic effects, but it can also have beneficial effects on cardiovascular diseases by increasing the bioavailability of nitric oxide and exerting an effect on nitric oxide mediator signals." - Nitric Oxide | 2024

"Distinguished by its unique molecular structure, curcumin exhibits potent biological activities including anti-inflammatory, antioxidant, and potential anticancer effects. The research points towards curcumin’s growing importance as a multi-faceted natural compound in the medical and scientific community. In the realm of contemporary science, curcumin has sparked considerable interest due to its potential health benefits. Studies have delved into its effectiveness against chronic illnesses such as cancer, Alzheimer’s disease, heart diseases, and inflammatory conditions. This interest is fueled by its properties as an antioxidant, anti-inflammatory, and role in cancer prevention. Scientists are examining how curcumin influences various cellular processes by interacting with multiple signaling molecules, including growth factors, cytokines, and the genes involved in cell life cycle and division. In summary, curcumin, with its deep-rooted history in traditional healing practices and its promising prospects in modern medical research, continues to be an area of keen scientific focus. As research progresses to elucidate the complexity of its chemistry and the breadth of its pharmacological actions, curcumin stands as a key player in the treatment of a diverse spectrum of health conditions." - International Journal of Molecular Sciences | 2024

"Curcumin is one of the most powerful natural anti-inflammatories in existence." - Curcumin in Alzheimer’s Disease and Depression | 2024

"Intensive studies carried out within the past 3 decades confirmed that the anti-inflammatory and antitumor properties of turmeric are attributable to its active component, curcumin. Curcumin is a natural compound isolated from the rhizome of the plant Curcuma longa (turmeric) that has been used to treat inflammation, cancer and neurodegenerative diseases such as multiple sclerosis (MS) and Parkinson’s disease. A large number of studies including both animal model experiments and clinical trials, have verified the anti-inflammatory and immunomodulatory properties of curcumin." - Frontiers in Pharmacology | 2024

"Almost 7000 scientific papers on turmeric and almost 20,000 on curcumin have been published in PubMed. These studies show that the golden spice has enormous health and medicinal benefits for humans." - Pharmacology & Translational Science | 2023
 
Where to purchase Curcumin?
Since 2000, TURMERIC-CURCUMIN.COM has offered Curcumin 95% extract supplements to research institutions, physicians, and university medical centers. Quality control tests, laboratory analysis certification, and rigorous cGMP manufacturing standards all ensure freshness, potency, and purity of contents. Orders are shipped FedEx or USPS Priority Air for fast and secure delivery. Contact service@turmeric-curcumin.com for bulk ordering, private labeling, contract manufacturing or any other questions. Multiple bottle orders will receive increasing quantity discounts listed below. Case purchases (12 bottles) will also receive free US shipping.


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200 capsules per bottle, 500 mG OF Curcumin 95% per capsule.

 Our label clearly indicates the contents (curcumin extracted from turmeric root), purity (95% standardized), amount per capsule (500mg) and number of capsules per bottle (200). Each 12-bottle case contains over 2.6 lbs (1.2 kg) of curcumin 95% turmeric root extract. Since 2000, the geographical source of our curcumin extract is turmeric grown in India. Within India, we are extensively networked with selected pesticide-free farms in the Eastern Ghats highlands, known for turmeric with the highest natural curcumin content in the world, at 8.8% and the West Jaintia Hills of Meghalaya, India, where Lakadong turmeric is one of the world's finest with a curcumin content of about 7.5%. From this high quality turmeric (Curcuma longa) root, we extract curcumin to a minimum 95% concentration. Within this extraction is the full spectrum of curcuminoids - curcumin, demethoxycurcumin, and bisdemethoxycurcumin - in their natural composition ratio of 76:19:5 for maximum potency. This is the same extract used in clinical trials and medical studies, free of added chemicals, treatments, unknown "formulas", "complexes" or "proprietary blends" which do not even disclose how much of each ingredient the product contains. Our supplement contains just two active ingredients; 500mg Curcumin 95% and 5mg of Piperine. You will receive a 100% natural, additive-free product. There are no synthetics, no starch, no sugars or sweeteners, no artificial colors or flavors, no sodium, no soy, no yeast, no wheat, no corn, no rice or other grains, no gluten, no dairy, no preservatives, no gums, no dyes, and no GMO.

What is the suggested usage?

"For optimal pharmacological effects, an oral dose of more than 8.0 grams per day is often required. Numerous clinical studies demonstrated that a daily intake of 12 grams of curcumin is well tolerated and safe." - Pharmaceutics | 2024

"Patients taking curcumin once or twice a day reported significant symptom improvement compared to patients taking it sporadically." - Rheumatology International | 2024

"Researchers concluded that if you want to receive the maximum benefits from curcumin, 30 mg per kilogram body weght is the most effective dose." - Molecular Neurobiology | 2024

"Curcumin's protective effect is proportional to the dose, and the efficacy may be further increased at a concentration of more than 200 mg per kg. Results indicated that the efficacy of curcumin improved with higher administered doses within the concentration range of 200 mg per kg. The results from the fitted curves suggest that efficacy may further improve at concentrations exceeding 200 mg/kg." - Cardioprotective Effects of Curcumin Against Diabetic Cardiomyopathie | 2024

"A phase I trial examining the impact of curcumin on advanced colorectal cancer did not detect curcumin concentration in the plasma at lower doses. However, metabolites of curcumin were identified in plasma at higher doses." - Food Chemistry | 2024

"In a study on curcumin treatment of drug-resistant tumor cells, a low dose of curcumin showed no effect on antioxidant proteins, whereas a high dose resulted in the inhibition of antioxidant proteins. Furthermore, high-dose curcumin treatment has been reported to exacerbate the effects on damaged mitochondria. This results in mitochondrial and DNA damage and subsequent activation of the cell death pathway, providing possible approaches for cancer therapy." - Oncology Letters | 2024

"A study used two dosages (2000 mg and 4000 mg) of curcumin powder daily for 30 days in 40 participants, aiming to decrease procarcinogenic factors. Only the higher dose group showed a 40% reduction in these foci, correlating with a significant increase in plasma curcumin levels." - Curcumin in Cancer and Inflammation | 2024

"Curcumin supplementation in doses of 3000 mg/day over 8–12 weeks showed reductive effect on total cholesterol levels, however curcumin therapy with doses less of 1000 mg per day has had no significant effect." - Complementary Therapies in Medicine Volume | 2024

"The US Food and Drug Administration has permitted curcumin's safety. Because of multiple medical research on the safety and harmfulness of curcumin, a tolerable dosage of 4 – 8 grams per day is regarded to achieve the best therapeutic results" - Food and Agricultural Immunology | 2023


"The dose-dependent action of curcumin observed in our results highlights the importance of considering its concentration in cancer treatment. We found that increasing concentrations of curcumin led to a proportional decrease in cell viability, migration, and invasion in gastric cancer cells. This suggests that the efficacy of curcumin in inhibiting cancer cell progression is influenced by its dose, with higher concentrations resulting in more pronounced effects. The dose-dependent response may be attributed to curcumin's complex interactions with multiple cellular targets and signaling pathways. At lower concentrations, curcumin may predominantly target specific pathways, while higher concentrations may engage multiple pathways, leading to a more potent inhibitory effect." - Dose-Response | 2023

 

how are  "curcumin" products deceptively marketed and advertised?

When selecting a curcumin extract product, it is important to know the difference between curcumin and turmeric. Turmeric root contains only 3% curcumin on average. Consumers may be misled by deceptive marketing to believe there is more curcumin per capsule than there actually is. Unfortunately, these deceptions are not uncommon in the supplement industry today:

HeartWise Inc., doing business as NatureWise, was hit with a class action lawsuit for falsely advertising that its dietary supplements contain “2250 mg Per Day” of curcumin, when each pill actually only contains 750 mg. Plaintiff Martha Valentine says the dietary supplement actually requires three capsules to provide the advertised 2250 mg dosage. She maintains that she was led to believe each of the 180 capsules in the container contains 2250mg of the curcumin supplement after reading and relying on the product’s label that represented “2250 mg Per Day” of curcumin and “180 vegetarian capsules.” She says that at the time of her purchase, she did not know the product required her to take three capsules to reach the full dosage of 2250 mg of curcumin, and if she had known the truth regarding NatureWise’s misrepresentations and omissions, she would not have purchased the product. She maintains that this representation led her to believe that each of the capsules contained 2250 mg of the curcumin supplement. However, upon closer inspection of the bottle, NatureWise reveals that three capsules must be consumed to provide the 2250 mg per day serving. NatureWise’s misleading representations and omissions lead consumers to pay a premium for the supplements because they falsely believe that they are receiving three times as much curcumin as they actually receive in each bottle. “NatureWise intentionally fails to adequately disclose to consumers that more than one capsule is required to obtain the labeled dosage amount. Defendant knew and intended that consumers would purchase, and pay a premium for, a supplement labeled as having a 2250 mg of curcumin per day, leading consumers to believe that by taking 1 capsule per day they would be able to get all the benefits of consuming a large dosage of curcumin." - Valentine et al v. HeartWise Inc. d/b/a NatureWise and HeartWise Wonder Inc., Case No. 20-cv-4302, N.D. Cal.

Sam’s West Inc's Member’s Mark supplements was hit with a class action lawsuit on March 23, 2023 in a Tennessee federal court for falsely advertising its turmeric curcumin complex health supplement. According to the lawsuit filed by plaintiff Matthew Casella, the product’s front label representations say it contains 500 mg of “standardized extract” of “turmeric curcumin complex” and the Supplement Facts on the back label specify that “95% Standardized Turmeric (Curcuma longa) Extract” was used. These representations give consumers the impression the product contains 95% (475mg) of curcuminoids per serving, Casella says. “However, lab testing conducted by ConsumerLab.com revealed that instead of the expected 475 mg, the product contains only 9.7 mg of curcuminoids per serving,” he alleges. The ingredients list states that “CurcuWIN Turmeric Extract” is the extract used, however a report from ConsumerLab found that “CurcuWin is only 20% curcuminoids.” If the product contains CurcuWIN, as listed in the ingredients, the extract cannot also be “95% Standardized Turmeric (Curcuma longa) Extract,” as listed in the supplement facts, Casella reasons. “As a result of the false and misleading representations, the product is sold at premium price.” - Matthew Casella, et al. v. Sam’s West Inc., Case No. 3:23-cv-00102, in the U.S. District Court for the Eastern District of Tennessee.

"Doctor's Curcumin" on the front of the label, but the details confirm that each capsule is 100% turmeric spice.

"Turmeric Curcumin 500mg Enhanced Formula" only contains 200mg Curcumin extract, and the remainder is 300mg turmeric.

"1000mg Super Complex Curcumin (25%)" is actually just 250mg of Curcumin extract and the remaining 750mg is turmeric.

"Turmeric Curcumin Proprietary Blend 1000mg" but contains only 50mg Curcumin 95% extract per capsule, or 3,000mg per bottle (60 capsules x 50mg) and yet is priced higher than our bottle, which contains a total of 100,000mg of Curcumin 95% extract.

"Premium Turmeric Curcumin Complex Plus 1500" contains 150mg of Curcumin and 600mg of turmeric spice per serving, and the serving size is two capsules, meaning only 75mg of Curcumin 95% extract per capsule.

Actual labels from "Curcumin" bottles:

  

does piperine improve absorption, enhance bioavailability, and work synergistically with Curcumin?

 
"The association with piperine, an alkaloid derived from black pepper (Pipernigrum L), is capable of increasing the bioavailability of some drugs by inhibiting intestinal and hepatic glucuronidation. In humans, administration of 20mg of piperine with 2g of curcumin increased its bioavailability by 2000% compared to administration of 2g of curcumin alone. When curcumin (20 and 40mg/kg) was co-administered with piperine (bioavailability enhancer) at a dose of 2.5mg/kg, its pharmacological effects were intensified. Piperine is capable of increasing absorption, plasma concentration, and bioavailability of curcumin in both rats and humans without significant side effects. The administration of 20mg/kg of piperine with 2g/kg of curcumin in rats increases its bioavailability by 154% compared to administration of 2g/kg of curcumin alone. Piperine is a non-specific drug metabolism inhibitor, with low discrimination between different forms of cytochrome P-450. In rats, orally administered piperine strongly inhibits the hepatic activity of aryl hydrocarbon hydroxylase (AHH) and UDP-glucuronyl transferase, with a potent inhibitory effect on pharmacological metabolism." - Curcumin in Alzheimer’s Disease and Depression: Therapeutic Potential and Mechanisms of Action | 2024

“Piperine, the active compound in black pepper, can enhance curcumin absorption (from turmeric) by up to 2,000%. This synergy not only amplifies the benefits of curcumin for the brain but also helps in improving digestion and nutrient absorption, indirectly supporting cognitive health.” - NY Post | 2024

"Combining piperine with curcumin has been shown to increase curcumin bioavailability in  humans." - Food Chemistry | 2024

"Piperine, a bioactive compound from black pepper (Piper nigrum), emerges as a potentiation agent capable of inhibiting hepatic glucuronidation, thereby increasing curcumin bioavailability by up to 2000%. The combination of curcumin and piperine has shown successful outcomes in diseases where oxidative stress is a significant etiological factor, such as metabolic syndrome. Curcumin plus piperine group had significantly higher serum superoxide dismutasecompared to the placebo group. This study suggests that 12 weeks of curcumin plus piperine supplementation effectively enhances the enzymatic antioxidant defense in IBD patients. The results provide new insights into the use of a natural therapeutic strategy and underscore the effectiveness of its combination with piperine, in enhancing the antioxidant effects of curcumin." - Effect of Curcumin plus Piperine on Redox Imbalance and Inflammation in Inflammatory Bowel Disease Patients | 2024

"Curcumin and piperine supplementation before and after exercise positively affects the muscle damage of athletes after exercise." - Examination of the effect of curcumin supplementation on liver enzymes and some physiological parameters in volleyball players | 2024

"Curcumin plus piperine administration showed a significantly increased superoxide dismutase activity and glutathione levels while significantly decreased malondialdehyde concentrations. In addition, our study revealed that curcumin plus piperine significantly decreased tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 concentrations." - The Effects of Curcumin Plus Piperine Co-administration on Inflammation and Oxidative Stress | 2024

"The bioavailability of curcumin can be enhanced by piperine (an alkaloid derived from black pepper). Using piperine combined with curcumin significantly increased serum levels of curcumin in humans and animals by 2,000 times because of the extensive absorption and bioavailability." - The Use of Curcumin in the Treatment of Colorectal, Breast, Lung, and Prostate Cancers: An In Vivo study Update | 2024

"The combination of curcumin and piperine has shown successful outcomes in diseases where oxidative stress is a significant etiological factor, such as metabolic syndrome. The results underscore the effectiveness of combination with piperine in enhancing the antioxidant effects of curcumin. Piperine, a bioactive compound from black pepper (Piper nigrum), emerges as a potentiation agent capable of inhibiting hepatic glucuronidation, thereby increasing curcumin bioavailability by up to 2000%. The curcumin plus piperine group had significantly higher serum SOD compared to the placebo group. This study suggests that 12 weeks of curcumin plus piperine supplementation effectively enhances the enzymatic antioxidant defense, particularly SOD, in inflammatory bowel disease patients." - Effect of Curcumin plus Piperine on Redox Imbalance and Inflammation in Inflammatory Bowel Disease Patients | 2024

"When analyzed in humans, 2 grams of isolated curcumin showed undetectable or very low serum levels. After the concomitant administration of 20 mg of piperine, an increase in concentrations was observed within the time frame of 0.25 to 1 hour after administration. In those rats in which piperine pre-administration was performed before receiving curcumin, there was a significant increase in the oral bioavailability of curcumin, especially at 6 hour after piperine administration. Piperine, when administered concomitantly with 2 grams of curcumin in healthy human volunteers, increased the curcumin bioavailability by 2000%. Curcumin and piperine supplementation for obese mice under caloric restriction may increase the loss of body fat and suppresses HFD-induced inflammation." - Antioxidants | 2024

"Both curcumin and piperine suppress proliferation of leukemia cells and their IC50 value has reported to be 30 μM and 25 μM, respectively. These anti-cancer agents have capacity of inducing apoptosis in leukemia cells via mitochondrial pathway. Besides, curcumin and piperine induce autophagy and mediate S arrest.The current section clearly demonstrated that curcumin and its combination with other therapies can suppress leukemia progression." - Journal of Herbal Medicine, The Effects of Curcumin on Neurodegenerative Diseases: a Systematic Review | 2024

"To improve the bioavailability of curcumin, one of the potential strategies is adding piperine when administering curcumin orally. Piperine also has antioxidant, immunomodulatory, and anti-inflammatory activities. Piperine can increase the in vivo bioavailability of curcumin by inhibiting its metabolism and reducing the required dose of curcumin in the clinical setting. Piperine binds to several areas of the enzyme to form a hydrogen bond complex with curcumin that can increase its bioavailability up to twenty times." - Vitamin D and Curcumin Piperine Attenuates Disease Activity and Cytokine Levels in Systemic Lupus Erythematosus Patients | 2024

"Studies have shown that combining curcumin with piperine, a compound found in black pepper, can increase its bioavailability by inhibiting metabolism." - PLoS One | January 2024

"Black pepper (Piper nigrum) family piperaceae, with the main active ingredient piperine, has a hypoglycemic effect (Panda & Kar, 2003). Turmeric (Curcuma longa), family Zingiberaceae, in which a vital active ingredient is curcumin, has been revealed to have hypoglycemic, antioxidant, and lipid-lowering effects in many investigational studies (Khaliq et al., 2015). Earlier studies revealed that both herbs work in synergy in lowering postprandial blood glucose levels It was hypothesized that black pepper and turmeric together have a greater effect on lowering postprandial glycemia." - A Review on the Extraction Process and Therapeutic Activity of Curcumin on Diabetes Mellitus and Cancer | 2024

"Piperine enhances bioavailability when combined with curcumin in a complex. This was connected previously with 2000% increase in curcumin bioavailability. Several organic compounds have also been utilized to boost curcumin bioavailability, the majority of which reduce the metabolism of curcumin and enhance its absorption. Most of these compounds were developed to slow down the metabolism of curcumin and improve its bioavailability. Piperine, the primary active component of black pepper, is the most widely used." - Biomedicine & Pharmacotherapy | 2024

"Piperine has been found to increase the bioavailability of curcumin significantly. Curcumin (oral, 1 g/d plus piperine 10 mg/day for 12 weeks) reduced cardiovascular risk and enhanced antioxidant capacity in type 2 diabetes mellitus through decreasing serum levels of total cholesterol and non-HDL-cholesterol." - Pharmacological Research | 2023

"Piperine increased the bioavailability of curcumin by 154%. Curcumin combined with piperine exhibited higher intestinal absorption (78%). When co-administered with piperine, the half-life of curcumin was increased from 12.8h to 28.9h. Co-administration of piperine (20 mg/kg) and curcumin (2 mg/kg) increased the plasma concentration of curcumin in a short time, i.e. within 1-2h, peak time was increased, elimination half-life decreased, and clearance decreased.  In humans, even with a 2g load of curcumin, the serum level was undetectable. A higher extent of absorption and higher bioavailability of curcumin (2000%) was observed in humans using 20mg piperine." - Review of Curcumin and Its Different Formulations: Pharmacokinetics, Pharmacodynamics and Pharmacokinetic-Pharmacodynamic Interactions | 2023

"Piperine is known to enhance curcumin absorption and tissue uptake, while also reducing curcumin hepatic metabolism. Once absorbed, curcumin is metabolized within the epithelial cells and/or effluxed back into the intestinal lumen. This efflux is thought to occur due to the presence of efflux transporters within the intestinal cell membranes. Piperine from black pepper, as well as certain catechins from green tea, are able to inhibit these transporters, thus increasing the amount of curcumin that remains in the body. A preclinical study administrated an orally delivered powder of curcumin (2 g/kg/day) and piperine (20 mg/kg/day) and concluded that piperine significantly increases the serum concentration of curcumin, resulting in a 154% improvement in its relative bioavailability. Similarly, a clinical study conducted with the combined oral administration of curcumin and piperine dissolved in water (2 g of curcumin powder, 20 mg of piperine and 150 mL of water). The study found that piperine significantly increased the serum concentration of curcumin, resulting in a relative bioavailability increase of 2000%" - Effect of Curcumin Consumption on Inflammation and Oxidative Stress in Patients on Hemodialysis: A Literature Review | 2023

"The bioavailability of curcumin was significantly increased by 2000% when piperine, which is extracted from black pepper, was also taken as a supplement." - Effect of Curcumin and Coenzyme Q10 Alone and in Combination on Learning and Memory in an Animal Model of Alzheimer’s Disease | 2023

"Piperine is an adjuvant that can greatly improve bioavailability of curcumin. Piperine slows the metabolism of curcumin by inhibiting hepatic and intestinal glucuronidation. Previous studies have shown that administering curcumin with piperine can increase serum concentrations of curcumin by up to 2000%, indicating that glucuronidation inhibition may be the major mechanism of increasing curcumin bioavailability. As such, the formulation of the supplement administered in the current study, 1,400 mg of curcumin and 10 mg of piperine, may have helped to increase serum concentrations of curcumin such that it could exert its biological action." - Frontiers in Nutrition, Sport and Exercise Nutrition | 2023

"The study has found that curcumin (oral, 1 gram per day plus piperine 10 mg/day for 12 weeks) reduced cardiovascular risk and enhanced antioxidant capacity in T2DM through decreasing serum levels of TC, non-HDL-c and MDA, while also increasing serum adiponectin, SOD or HDL-C levels." - Pharmacological Research | 2023

"The combination of curcumin with piperine has better gastrointestinal absorption and reduces curcumin's systemic excretion. Piperine increases the bioavailability of curcumin by binding to the enzyme glucuronidase in the intestine, preventing glucuronidation and reducing the excretion of curcumin from the stool" - The effect of curcumin-piperine on cardiometabolic, inflammatory and oxidative stress factors and macular vascular density | 2023

"Curcumin + piperine decreased waist circumference, systolic blood pressure, total cholesterol, low-density lipoprotein-cholesterol, fasting blood glucose, alanine transaminase and aspartate transaminase compared with placebo. Curcumin + piperine may be considered as an adjunct therapy to improve anthropometric measures, blood pressure, lipid profile, blood glucose, and liver function in Non-alcoholic Fatty Liver Disease patients." - Efficacy of curcumin plus piperine co-supplementation in moderate-to-high hepatic steatosis | 2023

"Curcumin-piperine supplementation for 12 weeks resulted in significant reductions in serum levels of total cholesterol, triglycerides, weight, waist circumference, and systolic and diastolic blood pressure in patients. To improve pharmacokinetic features, co-administration of curcumin with piperine has been introduced as an alternative. Piperine, which is a naturally occurring alkaloid from pepper, has been shown to increase the bioavailability of curcumin and reduce its glucuronidation." - The effects of curcumin-piperine supplementation on inflammatory, oxidative stress and metabolic indices in patients with ischemic stroke in the rehabilitation phase: a randomized controlled trial | 2023

"Recent studies demonstrated that piperine potentiates curcumin’s inhibitory effect on tumor progression via enhancing its delivery and therapeutic activity. Among the numerous candidates tested so far, curcumin, piperine and certain types of cannabinoids performed promisingly well in colon carcinoma models as monotherapy agents. Piperine, a dietary polyphenol isolated from black and long peppers, distinguished with its intrinsic features, improves not only curcumin’s existing anti-cancer activity, but also its extremely poor bioavailability. As a single agent, piperine alone also displays anti-mutagenic and anti-tumor activities." - Frontiers in Pharmacology | 2023

"Several studies done by using curcumin in conjunction with various anticancer compounds, as in piperine...have shown significant suppression, reduction/inhibition of IL-6, IL-1β, IL-19, TNF-α and COX-2 (Al-Dossari et al., Citation2020; X. Q. Hu et al., Citation2016; Neyrinck et al., Citation2013; Tremmel et al., Citation2019; Yan et al., Citation2019)." - Curcumin: recent updates on gastrointestinal cancers | 2023

"Black pepper piperine is one of the most effective boosters of curcumin bioavailability. The simultaneous administration of curcumin and piperine to humans or animals boosted the serum levels by more than a thousandfold. Piperine contained in black pepper can improve the uptake of curcumin by 2,000% (20 times). The vast metabolism of turmeric in the hepatic tissues and intestinal walls increased its bioavailability, which improved through piperine. Taking these two substances with an oil rich in unsaturated fatty acids further strengthens this benefit. Zeng et al. examined the effect of piperine pre-administration on oral curcumin bioavailability. In this investigation, rats were given 20 mg/kg piperine first, followed by 200 mg/kg curcumin at intervals of 0.5–8 h after piperine treatment. The pre-treatment with piperine before curcumin administration significantly increased curcumin oral bioavailability in all tested rats. Recent research suggests that oral administration of curcumin and piperine for symptomatic COVID-19 therapy might dramatically reduce mortality and morbidity (53). The conjugation between piperine and curcumin may be a safe and natural option for preventing post-COVID symptoms." - Impacts of turmeric and its principal bioactive curcumin on human health: Pharmaceutical, medicinal, and food applications: A comprehensive review | 2023

"The combination of Curcumin with piperine was associated with a 2000% improvement in Curcumin bioavailability." - Health Science Reports | 2023

"Another promising approach is the simultaneous administration of curcumin with piperine, an alkaloid from black pepper and long pepper. Piperine significantly increases the bioavailability of curcumin—up to 2000%—by preventing its metabolism." - An Overview of the Enhanced Effects of Curcumin and Chemotherapeutic Agents in Combined Cancer Treatments | 2023

"Curcumin has received worldwide attention for its multiple health benefits, which are best achieved when curcumin is combined with agents such as piperine to increase its bioavailability significantly. Pawar et al reported that the administration of oral curcumin with piperine as symptomatic adjuvant therapy in COVID 19 treatment could substantially reduce morbidity and mortality and ease the logistical and supply related burdens on the healthcare system. Askari et al reported that 46 outpatients with COVID 19 disease were randomly allocated to receive two capsules of curcumin - piperine for 14 days. There was a significant improvement in dry cough, sputum cough, ague, sore throat, weakness, muscular pain, headache and dyspnoea in curcumin - piperine groups. Kumar et al reported that using curcumin, Piper Nigrum Piperine and catechin could cure and prevent COVID 19 outbreaks and infection. Curcumin and piperine interact and form a π–π intermolecular complex, which enhances curcumin's bioavailability." - Therapeutic potential of curcumin in ARDS and COVID 19 | 2023

"Curcumin by itself has very low bioavailability due to ineffective absorption, and fast metabolism and excretion. This issue can be solved by combining curcumin with piperine (a key active ingredient in black pepper) to create a curcumin complex that is readily absorbed and metabolized in the body. Curcumin is more active when combined with piperine to provide major health benefits. These benefits are maximized when curcumin is coupled with agents such as piperine, that significantly increase its bioavailability." - The Therapeutic Role of Curcumin in Inflammation | 2023

"Curcumin has received worldwide attention for its multiple health benefits, which appear to act primarily through its anti-oxidant and anti-inflammatory mechanisms. These benefits are best achieved when curcumin is combined with agents such as piperine, which increase its bioavailability significantly." - Department of Nutrition, Central Michigan University | 2023

Archived studies on curcumin and piperine
 

HAS THE SAFETY OF CURCUMIN 95% BEEN ESTABLISHED?

The safety, tolerability, and nontoxicity of curcumin at high doses has been well established by human clinical trials. The US FDA classifies Turmeric as GRAS (Generally Recognized As Safe).  Preclinical and clinical studies indicate that curcumin is well tolerated and the overwhelming safety profile of curcumin is evident. Before using any herbs or dietary supplements in amounts greater than usually found in foods, consult a health care provider.

"Clinical studies have shown that curcuminoids, including curcumin, bisdemethoxycurcumin, and demethoxycurcumin, have safety characteristics at daily doses of 4000–8000 mg at 95% concentration. The US Food and Drug Administration (FDA) has given curcumin the " generally recognized as safe" (GRAS) designation. Various studies have shown that curcumin is safe, well-tolerated, and useful in the prevention and treatment of a variety of chronic diseases, such as cancer, heart disease, diabetes, neurological disorders, skin conditions, liver complications, and infectious diseases." - Biomedicine & Pharmacotherapy | 2024

"Long-term studies have shown that curcumin is safe and protective when used in the diet. In one study, high doses of curcumin (8 g/day) do not cause side effects. In another study, curcumin was administered at doses up to 12 g/day for three months with no apparent toxicity." - Review of the Protective Mechanism of Curcumin on Cardiovascular Disease | 2024

"As an antioxidant, anti-infection, anti-inflammatory, and anti-tumor compound, curcumin has been approved by the United States Food and Drug Administration as a safe compound." - Molecular Neurobiology | 2024

"Curcumin has been demonstrated to be safe even when it is administered at high doses. A phase 1 human trial in which as much as 8000 mg of curcumin per day was administered for 3 months to patients with high-risk or premalignant lesions reported no toxic effects. No serious side effects were reported in RA patients receiving 500 mg of curcumin per day over a period of 8 weeks. Curcumin treatment has no obvious toxic effect on liver or kidney functions; therefore, curcumin is generally recognized as a safe compound by the U.S. Food and Drug Administration." - Frontiers in Pharmacology | 2024

"The European Food Safety Authority (EFSA) established an acceptable daily intake of curcumin at 3 mg/kg body weight. For optimal pharmacological effects, an oral dose of more than 8.0 g/day is often required. Numerous clinical studies demonstrated that a daily intake of 12 g of curcumin is well tolerated and safe." - Pharmaceutics | 2024

"Curcumin has been used as a dietary supplement for centuries and is considered pharmacologically safe." - International Journal For Multidisciplinary Research | 2024

"A series of authoritative international institutions, such as the Food and Drug Administration (FDA) in the USA and the Joint FAO/WHO Expert Committee on Food Additives, have confirmed the safety of curcumin in daily use and clinical treatment." - Toxics | 2023

"According to the Joint Nations and World Health Organization Expert Committee on Food Additives (JECFA), curcumin is regarded as a safe chemical and is hence appropriate for everyday dietary usage and can be taken by patients of any age for a longer period of time without experiencing any negative side effects." - Biomedicine | 2023

"Curcumin is one of the most promising anticancer agents as it combines high biological safety for normal cells/tissues with potent cytotoxic activity against various human cancers." - International Journal of Molecular Sciences | 2023

"According to the US Food and Drug Administration (FDA) report, curcumin has been considered as “Generally Recognized as Safe” (GRAS) even at doses between 4000 and 8000 mg/day" - Evidence-Based Complementary and Alternative Medicine | 2023

"The safety of curcumin and turmeric products has been confirmed by the Food and Drug Administration (FDA), the Food and Agriculture Organisation (FAO) and the World Health Organisation (WHO). Curcumin has shown a very promising safety profile. According to reports by JECFA (Joint Expert Committee on Food Additives of the United Nations and the World Health Organisation) and EFSA (European Food Safety Authority), the acceptable daily intake (ADI) of curcumin is 0–3 mg/kg body weight. Several studies in healthy volunteers have confirmed the safety and efficacy of curcumin." - An Overview of the Enhanced Effects of Curcumin and Chemotherapeutic Agents in Combined Cancer Treatments | 2023

"Curcumin has also been recognized as safe by the US Food and Drug Administration (FDA). In most studies, very few adverse effects or no severe adverse effects occurred with turmeric extract and curcumin supplements, showing that it’s well tolerated globally. None of the patients required rescue medication for adverse effects management. Overall, the benefits of Curcuma longa extract and curcumin supplementation were significantly greater than their risks. Therefore, it can be recommended for musculoskeletal conditions." - Safety and Efficacy of Turmeric (Curcuma longa) Extract and Curcumin Supplements in Musculoskeletal Health | 2023

"Curcumin has been shown to be safe in numerous human studies, with only minor toxicity associated with this polyphenol. Therefore, curcumin is increasingly being viewed as a biomolecule capable of being administered for an extended period without causing adverse effects. The findings of the current study indicate that there were no significant adverse events associated with the short term use of PPI and curcumin." - BMJ British Medical Journal | 2023

"Curcumin is labeled as safe by the Food and Drug Administration (FDA, USA), and has achieved therapeutic pursuit in treating metabolic diseases, immune-related diseases, and cancer, owing to its vast biological target and with practically no aftereffects. Curcumin is an active natural compound that exhibits therapeutic effects on different diseases, including antiviral, antibacterial, anti-amyloid, thrombo-suppressive, antiarthritic, antioxidation, anti-inflammatory, and anticancer, with minimal aftereffects. Curcumin is safe in humans and has chemopreventive and chemotherapeutic effects. In vitro experimental evidence indicates that curcumin has excellent anticancer ability and can target cancer via diverse mechanisms by modulating several cellular signal pathways." - Curcumin a Natural Phenol and Its Therapeutic Role in Cancer | 2023

"Genotoxicity and mutagenicity assessments suggest that curcumin extract does not induce DNA damage or mutations. Furthermore, carcinogenicity studies demonstrate no evidence of increased cancer risk associated with the curcumin extract." - Department of Nutrition, Central Michigan University | 2023

"The Joint Food and Agriculture Organization (FAO), World Health Organization (WHO) Expert Committee on Food Additives (JECFA) and the European Food Safety Authority (EFSA) allocated an acceptable daily intake (ADI) for curcumin of 3 mg/kg body weight." - Nutrients | 2022

"Curcumin is considered a safe compound and authorized as a GRAS compound (generally recognized as safe) by US FDA (United States Food and Drug Administration). It is well tolerated at a higher dose of 12g in humans. Cells treated with the curcumin-piperine combination at their EC90 concentration showed no toxicity to neuronal cells. Reduction in locomotive behaviors was not observed with the curcumin-piperine combination, indicating no potential CNS side effects of curcumin-piperine combination at its highest therapeutic doses. We found no effects of the combination on the spontaneous locomotor activity at their high doses. The results indicate no potential central nervous system (CNS) side effects of the curcumin and piperine combination." - CM Journal | 2022

"Curcumin is “generally recognized as safe” (GRAS) as a dietary supplement by the U.S Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA) and has been catalogued with the E100 code of the European Union." - Curcumin: A Novel Way to Improve Quality of Life for Colorectal Cancer Patients? International Journal of Molecular Sciences | 2022

"According to the US Food and Drug Administration, curcumin is classed as safe for both human consumption and pharmacological purposes without any known side effects." - Life | 2022

"Studies have shown that systemic exposure to curcumin-containing products at doses of up to 8,000 mg/day was safe and tolerable and did not cause serious adverse events." - Curcumin (Curcuma, Turmeric) and Cancer, PDQ Integrative, Alternative, and Complementary Therapies Editorial Board | 2022

"According to relevant clinical trials on safety and toxicity, the acceptable dose of curcumin for maximum efficacy is 4 – 8 grams per day. It has been reported that humans can tolerate treatment with curcumin at a dose up to 12 grams per day." - Frontiers in Pharmacology | 2022

"The US Food and Drug Administration has marked curcumin as a "By and large Recognized As Safe" item. The United Nations and World Health Organization Expert Committee on Food Additives and European Food Safety Authority suggested the everyday admission of 0-3 mg/kg body weight of curcumin. Furthermore, curcumin supplementation in a few clinical preliminaries exhibited wellbeing profiles at dosages in the range of 4000 and 8000 mg/ day." - Journal of Antimicrobial Agents, Prevention of Female Reproductive Disorders with the Help of Curcumin | 2022

Archived studies on the safety of curcumin

 
Why NATURAL curcumin 95% extract from turmeric root without nanoparticles or other highly processed synthetics, liposomals or emulsifiers?
"The use of curcumin in liposomal form is becoming more and more common, the concentration of this compound, in cells can reach much higher level, definitely exceeding the amounts that can enter the body when applied in natural form. The conducted experiments clearly showed that liposomal curcumin, when directly applied to cells, is toxic to them. Comparison of the toxicity of curcumin for HL-60 cells and nerve cells confirmed (as shown in model studies) that the disruption of membrane structure due to the presence of liposomal curcumin correlates with damage to native membranes, ultimately leading to cell death." - Scientific Reports | 2024

"In the last few years questions have been raised regarding the potential toxicity of carbon nanotubes (CNTs) to humans and environment. It is believed that the physico-chemical characteristics of these materials are key determinants of CNT interaction with living organisms, and hence determine their toxicity." - Determinants of carbon nanotube toxicity | 2023

"This study evaluated the toxic events of curcumin nanoparticles with alterable surface polarity in alveolar macrophages. In conclusion, the cytotoxicity of curcumin nanoparticles on alveolar macrophages is surface-charge dependent, which in turn is associated to the uptake pathway and localization of curcumin nanoparticles in cells." - Toxicity of curcumin nanoparticles towards alveolar macrophage, Food and Chemical Toxicology | 2022

"The harmfulness of nanoparticles is impacted by their condition of conglomeration and mechanical properties, which are reliant upon their creation and decontaminating strategies. Worries about the poisonousness of nanoparticle-based conveyance strategies incorporate neuroinflammation, excitotoxicity, and unfavorably susceptible responses." - Alternative & Integrative Medicine | 2022

"Curcumin nanomicelle suppressed spermatogenesis, increased immunoreactivity of 8-oxodG, stimulated the Hsp70–2a and Hsp90 expressions, and resulted in severe DNA and mRNA damages. Moreover, the curcumin nano-micelle received animals exhibited remarkable reductions in the spermatozoa count, motility and DNA integrity. In conclusion, chronic and high dose consumption of curcumin nanomicelle results in remarkable oxidative stress." - Curcumin nano-micelle induced testicular toxicity in healthy rats; evidence for oxidative stress, Biomedicine & Pharmacotherapy | 2021

"A number of nanoparticles have negative impacts on male germ and somatic cells which could ultimately affect fertility or the ability to produce healthy offspring." - Toxicity mechanisms of nanoparticles in the male reproductive system | 2021

"Nanoparticles may act as reproductive toxicants depending on several factors, and induce damage to the male reproductive system by affecting the seminiferous tubules and spermatogenesis. This is mainly due to the fact that nanoparticles can easily enter the blood circulatory system and reach the testes by crossing the blood testes barrier. The bioaccumulation of nanoparticles in the testes causes seminiferous tubule histopathology and severely affects the sperm number, motility and morphology. Moreover, nanoparticles also induce disturbances to the Leydig cells, causing decline in the testosterone level with consequent testicular injury and reduced sperm production." - Perspectives of Nanoparticles in Male Infertility: Evidence for Induced Abnormalities in Sperm Production |  2021

"Curcumin nanoparticles suppressed the proliferation of testicular cell lines in vitro. In the present study, we disclosed the acute damage on mouse spermatogenesis and sperm parameters by nano-curcumin. Our results suggested that the reproductive toxicity of nanoformulated curcumin needs to be prudently evaluated before its application." - Acute Damage to the Sperm Quality and Spermatogenesis in Male Mice Exposed to Curcumin-Loaded Nanoparticles, International Journal of Nanomedicine | 2020


"Nanoparticles are able to pass certain biological barriers and exert toxic effects on crucial organs, such as the brain, liver, and kidney. Only recently, attention has been directed toward the reproductive toxicity of nanomaterials. Nanoparticles can pass through the blood–testis barrier, placental barrier, and epithelial barrier, which protect reproductive tissues, and then accumulate in reproductive organs. nanoparticles accumulation damages organs (testis, epididymis, ovary, and uterus) by destroying Sertoli cells, Leydig cells, and germ cells, causing reproductive organ dysfunction that adversely affects sperm quality, quantity, morphology, and motility or reduces the number of mature oocytes and disrupts primary and secondary follicular development. In addition, nanoparticles can disrupt the levels of secreted hormones, causing changes in sexual behavior. However, the current review primarily examines toxicological phenomena. The molecular mechanisms involved in nanoparticles toxicity to the reproductive system are not fully understood, but possible mechanisms include oxidative stress, apoptosis, inflammation, and genotoxicity. Previous studies have shown that nanoparticles can increase inflammation, oxidative stress, and apoptosis and induce ROS, causing damage at the molecular and genetic levels which results in cytotoxicity." - Potential adverse effects of nanoparticles on the reproductive system

"Recent studies have shown that nanoparticles disturb the developing oocyte by invading the protective barrier of theca cells, granulosa cell layers and zona pellucida. Nanoparticles disrupt sex hormone levels through the hypothalamic–pituitary-gonadal axis or by direct stimulation of secretory cells, such as granule cells, follicle cells, thecal cells and the corpus luteum. Some nanoparticles can cross the placenta into the fetus by passive diffusion or endocytosis, which can trigger fetal inflammation, apoptosis, genotoxicity, cytotoxicity, low weight, reproductive deficiency, nervous damage, and immunodeficiency, among others." - Nanoparticles and female reproductive system: how do nanoparticles affect oogenesis and embryonic development

"Females are particularly more vulnerable to nanoparticle toxicity, and toxicity in this population may affect reproductivity and fetal development. Moreover, various types of nanoparticles have negative impacts on male germ cells, fetal development, and the female reproductive system." - Toxicity of Nanoparticles on the Reproductive System in Animal Models: A Review
 

What are the pharmacological actions of Curcumin?

First shown to have anti-bacterial activity in 1949, curcumin has since been shown to have anti-inflammatory, anti-oxidant, pro-apoptotic, chemopreventive, chemotherapeutic, anti-proliferative, wound healing, anti-nociceptive, anti-parasitic, and anti-malarial properties as well.  Numerous clinical and preclinical studies and trials evaluating curcumin's safety and efficacy have revealed its potential against a wide range of human diseases and ailments have been completed. These pathologies include diabetes, obesity, neurologic and psychiatric disorders, and cancer, as well as chronic illnesses affecting the eyes, lungs, liver, kidneys, and gastrointestinal and cardiovascular systems. Curcumin has also been shown to regulate numerous transcription factors, cytokines, protein kinases, adhesion molecules, redox status and enzymes that have been linked to inflammation. Growing experimental evidence reveals that curcumin exhibits multitarget biological implications signifying its crucial role in health and disease, with pharmacological effects against numerous diseases like neuronal, cardiovascular, metabolic, kidney, endocrine, skin, respiratory, infectious, gastrointestinal diseases and cancer. The ability of curcumin to modulate the functions of multiple signal transductions are linked with attenuation of acute and chronic diseases. Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn’s disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis.

Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Extensive preclinical studies over the past three decades have indicated curcumin’s therapeutic potential against a wide range of human diseases. In addition, curcumin has been shown to directly interact with numerous signaling molecules. These preclinical studies have formed a solid basis for evaluating curcumin’s efficacy in clinical trials. The clinical trials conducted thus far have indicated the therapeutic potential of curcumin against a wide range of human diseases. Curcumin has a potential to prevent and/or manage various diseases due to its anti-inflammatory, anti-oxidant and anti-apoptotic properties with an excellent safety profile. In contrast, the anti-cancer effects of curcumin are reflected due to induction of growth arrest and apoptosis in various premalignant and malignant cells. Curcumin reduces the risk of osteoporosis via amelioration of mitochondrial membrane function, PKB phosphorylation, microRNA-365 activation, osteoblasts proliferation. It reduced ulcerative colitis by inhibiting neutrophil chemotaxis. The gastroprotective effect is due to inhibition of acid release, amelioration of blood flow, angiogenesis and collagenization of gastric tissue. Curcumin shows hepatoprotective action due to inhibitory activity against NF-jB. Additionally, curcumin reduced liver marker enzymes, cholesterol levels and replication of hepatitis B and C viruses. Curcumin treatment reduces asthma and allergy symptoms mainly due to inhibition of histamine release, attenuation of IgE, inhibition of COX-2 enzyme, suppression of JNK54/56, ERK 42/44 and p38 MAPK, stimulation of Nrf-2/HO-1 pathway, upregulation of Notch1, Notch2 receptors, GATA3 etc. Curcumin blocks certain cytokines and enzymes, inhibits ROS generation, downregulate NF-kB activation, induce extracellular matrix production, upregulate collagen and fibronectin expressions thereby reduce inflammatory diseases. Curcumin treatment reduces fibronectin and collagen IV expressions, suppresses TGF-bsignaling and exhibits antioxidant, anti-inflammatory and anti-apoptotic potential thereby ameliorates kidney functions. Studies have indicated the anticancer effects of curcumin by evaluating its effect on a variety of biological pathways involved in cell cycle regulation, apoptosis, tumorigenesis, mutagenesis and metastasis.

Curcumin mediates its effects by modulation of various molecular targets including transcription factors, enzymes, cell cycle proteins, receptors, cell surface adhesion molecules, neurotransmitters etc. Curcumin exhibits antioxidant, anti-inflammatory and anti-apoptotic potential thereby reduce neurodegenerative, cardiovascular, metabolic, gastrointestinal, respiratory and inflammatory diseases. Clinical and preclinical data have conclusively proved that curcumin modulates neurotransmitter levels and reduces neurodegeneration thereby ameliorate neuronal and behavioral dysfunctions. Curcumin reduces Alzheimer’s pathology by reducing Abplaques and tau phosphorylation. The anti-depressant and anxiolytic mechanism of curcumin includes inhibition of brain MAO activity, modulation of serotonin receptor and amelioration of neurotrophic factors. Curcumin reduces drug addiction and withdrawal symptoms, possibly through modulation of HAT, DNA methyl transferases, CREB, BDNF and CaMKIIalevels. Curcumin administration reduced Huntington’s disease by reducing huntingtin aggregates. In cardiovascular disease, the anti-atherosclerotic mechanism of curcumin includes the inhibition of platelet aggregation and modulation of cholesterol homeostasis. Curcumin effectively reduce hypertension by blocking angiotensin I receptor, reducing circulating angiotensin-converting enzyme and inducing vasodilation. The antiarrhythmic mechanisms of curcumin are due to modulation of Ca 2þ homeostasis and blockade of potassium channels. The anti-fungal mechanisms of curcumin includes the leakage of intracellular component, disruption of plasma membrane, generation of oxidative stress, induction of apoptosis, inhibition hyphae development, upregulation of chitin synthase and PKC etc. Curcumin treatment downregulated genomic transcription and translation, inhibited viral oncoproteins, suppressed the Akt/SREBP-1 pathway, inhibited hemagglutination, proteases, integrase and Tat protein acetylation resulting in antiviral effects. Curcumin administration reduces cerebral infracts size and volume during stroke. During metabolic diseases, curcumin treatment ameliorates b-cell dysfunction, insulin signaling and GLP-1 secretion while reduces glucose intolerance, hyperglycemia, hyperinsulinemia and hyperlipidemia.
 
what studies and research papers on Curcumin have been published in medical literature and scientific journals?

July 2024

Curcumin for COVID-19: 27 studies from 240 scientists and 14,886 patients in 11 countries
C19early.org | July 2024
Curcumin reduces risk for COVID-19 with very high confidence for mortality, hospitalization, recovery, and in pooled analysis, high confidence for viral clearance. Statistically significant improvements are seen for mortality, hospitalization, progression, recovery, and viral clearance. 18 studies from 16 independent teams in 8 countries show statistically significant improvements. Meta analysis using the most serious outcome reported shows 44% lower risk. Results are similar for Randomized Controlled Trials, higher quality studies, and peer-reviewed studies. Other meta analyses for curcumin can be found showing significant improvements for mortality, hospitalization, recovery, and symptoms.

Possible use of Curcuma longa extract as a post-chemotherapeutic supplement in acute myeloblastic leukaemia
International Journal of Clinical and Diagnostic Pathology | July 2024
Curcumin, a polyphenolic compound from Curcuma longa, is well known for its anti-inflammatory, antioxidant, and anticancer properties. These findings suggest that curcumin possesses potent cytotoxic effects on leukemia cells and could serve as a valuable adjunct in leukemia therapy. Further research, including clinical trials, is necessary to evaluate the safety and efficacy of curcumin in leukemia patients and to explore potential synergistic effects with existing chemotherapy agents. This study delineates the potential of curcumin as a less toxic and more effective therapeutic option for leukemia. In conclusion, our research aligns with previous findings and offers a detailed analysis of curcumin's significant anti- AML properties. Curcumin's capacity to trigger apoptosis, suppress cell proliferation, and hinder the spread of AML cells underscores its potential as a therapeutic agent. This study highlights the promise of curcumin as a potent weapon in the battle against acute myeloid leukemia.

Accelerate muscle recovery with curcumin? This is how you do it
Ergo-log.com | July 2024
Supplementation with curcumin accelerates recovery from exercise-induced muscle damage, this web magazine has reported several times. A Chinese meta-study, published in PLoS One, tells athletes how to best use curcumin Researchers from Huaqiao University traced 14 previously published trials in the scientific literature, in which researchers had subjects exercise intensively - in most cases this involved strength training - and determined the effect of curcumin supplementation on muscle recovery. The researchers looked at, among other things, the effect on muscle soreness. The figure below shows that supplementation with curcumin significantly reduced muscle pain.

 Curcumin protects against cadmium-induced germ cell death in the testis of rats
Toxicology Research | July 2024
Overall, our data suggest that cadmium induces germ cell apoptosis through mitochondrial-induced oxidative stress, but curcumin pretreatment offers strong protection against cadmium-induced reproductive toxicity.

Common spice could help fight off cancer and reduce signs of ageing
Express | July 2024
Curcumin. It has such powerful anti-inflammatory effects that some studies even suggest the effects of curcumin are comparable to those of some pharmaceutical drugs. Curcumin has also been shown to increase the body's antioxidant capacity. Oxidative damage and free radicals are believed to be one of the mechanisms behind accelerating signs of aging and several chronic diseases. Curcumin, a key polyphenol found in food, plays a crucial role in lowering oxidative stress and balancing different bodily functions. It has the ability to decrease intracellular lipid peroxidation and enhance the body's antioxidant capabilities for a longer lifespan. Other studies have also demonstrated that taking curcumin supplements can help protect the hippocampus, which is responsible for learning and memory functions in the brain.Curcumin, the active ingredient in turmeric, may also kill isolated cancer cells in a test tube and prevent the growth of new blood vessels in tumors, limiting their ability to spread. Golden milk may be good for your brain, too. Studies show that curcumin may increase levels of brain-derived neurotrophic factor (BDNF). BDNF is a compound that helps your brain form new connections and promotes the growth of brain cells. Curcumin may help reduce symptoms of depression, too. Adding in a few grinds of black pepper will unlock extra health benefits that would otherwise be lost. The common table seasoning contains piperine - a natural substance that enhances the absorption of curcumin by 2,000%.

Meta-analysis of the effect of curcumin supplementation on skeletal muscle damage status
PLOS One | July 2024
Curcumin supplementation significantly mitigates skeletal muscle damage, with notable improvements in CK levels, muscle soreness, IL-6 levels, and ROM. Curcumin’s potential impact on chronic inflammatory conditions like metabolic syndrome, arthritis, and cancer has been thoroughly researched in recent decades. Curcumin is renowned for its myriad health benefits, including antioxidant, anti-inflammatory, and analgesic effects, which make it a highly popular supplement. Extracted from turmeric and approved for use as a food additive in China, curcumin activates SIRT1, potentially reducing inflammatory responses and protecting cardiovascular health. It also inhibits COX-2 and NF-kB signaling pathways while enhancing adaptability to training, offering similar benefits to NSAIDs without their side effects. Its effectiveness in alleviating post-exercise inflammation has contributed to its growing popularity. The use of curcumin supplements, known for their anti-inflammatory properties, can reduce inflammation and relieve pain. Curcumin is known to potentially modulate the inflammatory response following muscle injury through its effects on the inflammatory cytokine interleukin-6 (IL-6). This cytokine plays a vital role in both muscle injury and repair processes. Supplementation with curcumin could potentially improve muscle function and joint flexibility. curcumin’s potent antioxidant properties enable it to neutralize ROS generated within the oxidative phosphorylation chain. These combined mechanisms contribute to curcumin’s effectiveness in reducing CK levels. Curcumin alleviates muscle soreness through multiple mechanisms, notably by inhibiting COX-2 expression, which reduces CK activity and prostaglandin release, thereby easing soreness. Meta-analyses have shown curcumin’s efficacy in reducing post-exercise muscle soreness. Whether taken before or after exercise, curcumin consistently reduces muscle soreness.

The effectiveness of turmeric supplementation in reducing low-density lipoprotein cholesterol in adults
Department of Healthcare and Behavioral Sciences, Medical Writing Certificate Program, University of California, San Diego Extended Studies, La Jolla, California, USA | July 2024
Curcumin has potential as a safe, inexpensive dietary supplement to support cardiovascular health. One study reported curcumin reduced LDL-C by a mean of 39.83 mg/dL. Panahi et al. provide a detailed review of the metabolic and cellular MoA of curcumin and statins, and point out that they both target the same specific nuclear receptors and enzymes while reducing LDL-C. The authors note that while statins are more efficient in lowering LDL-C, for some patients, they have adverse effects. The authors suggest that for such patients, a combination of a statin and curcumin could synergistically lower LDL-C to a desirable level, while requiring a lower dosage of the statin, which could reduce the risk of adverse effects, such as extreme muscle pain.

Integrating Network Pharmacology, Transcriptomics to Reveal Neuroprotective of Curcumin Activate PI3K / AKT Pathway in Parkinson’s Disease
Drug Design, Development and Therapy | July 2024
Curcumin restored the dyskinesia and dopaminergic neurons damage of MPTP-induced mice. Curcumin against Parkinson’s disease by regulating inflammation, oxidative stress, and aging. The mechanisms of these were associated with activation of PI3K / AKT pathway.  In conclusion, the neuroprotective mechanisms of curcumin activate PI3K / AKT pathway in Parkinson’s disease was revealed by our study. Recently, there has been increasing interest in using curcumin to prevent Parkinson’s disease. The mechanisms of curcumin to anti-Parkinson’s Disease may include antioxidant, Immune modulation, and the clearance of α-syn. Our previous study suggested that curcumin’s effectiveness in treating Parkinson’s disease was linked to the gut-brain axis. Recent reviews have increasingly suggested that curcumin targeting the PI3K/AKT signal pathway to protect dopaminergic neurons, while also inhibiting the activation of microglia. As a result, curcumin has shown promising potential in the treatment and prevention of Parkinson’s Disease. Either as antioxidants or modulators of cell signalling, the influence of curcumin on oxidative and inflammation balance are key. Consistent with our enrichment analysis results, the neuroprotective of curcumin on Parkinson’s disease depend on oxidative stress, inflammation and apoptosis of nerve cells has been demonstrated. However, there is no direct experimental evidence in vivo for curcumin exerts the effects of anti-oxidative stress, anti-inflammation and anti-apoptosis by activating the PI3K/AKT in Parkinson’s Disease. And AKT gene expression in the cell was the key role of anti-oxidative stress, anti-inflammation and anti-apoptosis. Finally, our study verified the PI3K/AKT pathway activated by curcumin in Parkinson’s disease. However, to further demonstrate curcumin protects through the activation of the PI3K/AKT pathway, our future study should be incorporated an inhibitor targeting the PI3K/AKT pathway. This has established a solid theoretical basis for the clinical application of curcumin in treating Parkinson’s disease.

Potential of Curcumin to Reduce Serum Nuclear Factor-Kappa B (NF-kB) Levels After High-Intensity Exercise
Retos Journal | July 2024
The group given curcumin after high-intensity exercise reduced serum NF-kB levels significantly (*p<0.05) compared to the placebo group. It can be concluded that the administration of curcumin at 400 mg after high-intensity exercise can reduce serum NF-kB levels. Curcumin is known for its active compounds that have anti-inflammatory activity (Boarescu et al. 2022). Curcumin is able to inhibit inflammation by modulating NF-κB signals and blocking TNF- α signals by activating protein responses in muscles (Srivastava et al. 2017; Venkata et al. 2012). The anti-inflammatory activity of curcumin also inhibits the production of pro-inflammatory eicosanoids which include prostaglandins and leukotrienes (Han, Zhang, and Li 2021; Petrone-Garcia et al. 2021; Zhu et al. 2019). Curcumin has been widely used to increase endurance and Maximal oxygen uptake VO2 max (Hamidie, Ali, and Masuda 2017). In addition, curcumin has been widely used in the medical world to accelerate wound healing (Sharma et al. 2018). Curcumin administered at a dose of 400 mg/day can reduce serum NF-kB levels. Based on the laboratory tests we conducted, we believe the reduction in pain intensity occurred due to the anti-inflammatory effect of curcumin which is able to modulate NF-kB signals and block TNF-a signals.  Reducing NF-kB levels is believed to lessen pro-inflammatory cytokines such as TNF-a and is closely related to muscle pain after exercise. We recommend using curcumin as a natural ingredient that can potentially reduce NF-kB.

Role of curcumin on beta-amyloid protein, tau protein, and biochemical and oxidative changes in streptozotocin-induced diabetic rats
Naunyn-Schmiedeberg's Archives of Pharmacology | July 2024
Results show that curcumin has an effect on reducing oxidative stress caused by diabetes and increasing antioxidant activity. The protective effect of curcumin is tested during induction and active diabetes. The results indicated that diabetic rats displayed increased levels of Aβ, tau protein, and total oxidant capacity (TOS) compared to the curcumin-treated groups. Additionally, the total antioxidant capacity (TAS) levels were lower in the diabetic rats (P < 0.05). Aβ protein levels are lower in both the serum and brain of rats with active diabetes and treated with curcumin compared to control rats (P > 0.05). In addition, serum TAS levels were higher in rats treated with curcumin following the induction of diabetes than pre-induction of diabetes (P > 0.05). The TOS levels in the serum were higher in the rats treated with curcumin during active diabetes compared to the rats treated prior to the induction of diabetes.

Curcumin as a regulator of Th17 cells: Unveiling the mechanisms
Food Chemistry: Molecular Sciences | July 2024
Curcumin possesses diverse pharmacological effects due to its interactions with various cells and molecules. Curcumin can inhibit Th17 proliferation and reduce the production of inflammatory cytokines. Curcumin, a polyphenol natural product derived from turmeric, possesses diverse pharmacological effects due to its interactions with various cells and molecules. Recent studies have highlighted its immunomodulatory properties, including its impact on immune cells and mediators involved in immune responses.  Curcumin exhibits anticancer, anti-inflammatory, and antioxidant characteristics (Chatterjee and Pandey, 2011, Marjaneh et al., 2018, Zahedi et al., 2023, Mohajeri and Sahebkar, 2018). In the past two decades, studies have found that curcumin has immunomodulatory effects, regulating the activity of immune cells. It can reduce the production and release of several proinflammatory cytokines, such as IL-12, TNF, and IL-6, by preventing the transcription of NF-κB (Jagetia, 2007). Recent reports have shown that curcumin can reduce the proliferation of alloreactive T cells and significantly suppress the differentiation of Th17 cells (Park et al., 2013). Curcumin inhibits the differentiation and development of Th17 cells through the downregulation of ORγt signaling, IL-21, and IL-6, as well as the inhibition of STAT3 phosphorylation. In summary, curcumin has the ability to hinder the differentiation and proliferation of Th17 cells by repressing the secretion of IL-23, IL-6, and IL-21. It also suppresses the production of pro-inflammatory cytokines, including IL-17 and TNF-α, in Th17 cells, thereby reducing the expression of inflammatory cells, particularly neutrophils, and resulting in decreased inflammation and infiltration (Haftcheshmeh et al., 2021). Curcumin demonstrates promise in regulating T cell subsets associated with inflammatory diseases. Xiao et al. (Xiao et al., 2022) reported that curcumin downregulated pro-inflammatory Th17 cells (CD4 + CCR6 + Th17, CD4 + IL-17A + Th17, IL-17A, BATF, C-Maf, RORγt) and upregulated anti-inflammatory Treg cells (CD4 + Foxp3 + Treg, CD4 + IL-10 + Treg, IL-10, Foxp3, Eomes) in mice with diabetic colitis, suggesting its ability to restore Th17/Treg balance. These findings highlight the potential of curcumin as a therapeutic agent for various inflammatory conditions by modulating T cell responses. Curcumin has been shown to significantly inhibit the proliferation of Th17 cells and reduce the production of inflammatory cytokines, including TNF-α, IL-22, and IL-17. Curcumin has several roles in the regulation of enzymes involved in inflammation, adhesion molecules, transcription factors, protein kinases, cytokines, and redox balance. It possesses various pharmacological functions, including antimicrobial, antitumor, anti-inflammatory, antiviral, antioxidant, and antifungal properties (Howells et al., 2021, Heidari et al., 2023, Bagheri et al., 2020, Cicero et al., 2020, Keihanian et al., 2018, Khayatan et al., 2022, Mokhtari-Zaer et al., 2018, Panahi et al., 2019, Sahebkar, 2010, Sahebkar, 2014, Iranshahi et al., 2010, Mohammadi et al., 2019, Panahi et al., 2012). It also plays a protective role against autoimmune diseases. Curcumin, an active compound found in turmeric, exhibits potent immunomodulatory effects, making it a promising therapeutic agent for various inflammatory and autoimmune disorders. Recent studies have focused on the ability of curcumin to modulate Th17-mediated immune responses, which play a critical role in the development of several autoimmune diseases. Curcumin has been shown to inhibit the proliferation and differentiation of Th17 cells and reduce the production of specific pro-inflammatory cytokines such as IL-17, IL-6, and TNF-α. Additionally, curcumin has been found to increase the production of Treg cells, which suppress excessive immune responses and maintain immune homeostasis. Overall, curcumin's ability to target the Th17 axis opens exciting avenues for developing novel therapeutic strategies for autoimmune and inflammatory diseases.

Ameliorative Effects of Curcumin on Type 2 Diabetes Mellitus
Moleculres | July 2024
Curcumin, the major curcuminoid of turmeric, is one of the most studied bioactive components of herbal supplements, which has a variety of biological activities. Clinical trials and preclinical research have recently produced compelling data to demonstrate the crucial functions of curcumin against type 2 diabetes mellitus via several routes. Curcumin, a natural polyphenol derived from the rhizome of Curcuma longa (turmeric), which has been widely used in cosmetics, food, and pharmaceutical industries, has gained growing interest in the last years for its pharmacological activities. Different studies demonstrated that curcumin has anti-oxidant, anti-inflammatory, antimicrobial, anti-atherosclerotic, nephroprotective, anticancer, hepatoprotective, immunomodulatory, antidiabetic, and antirheumatic effects, but with no toxicity. Numerous studies demonstrated that curcumin could improve insulin resistance, regulate blood lipid metabolism, decrease glucose and insulin levels, reduce the release of inflammatory factors, inhibit oxidative stress, and regulate gut microbiota in patients with type 2 diabetes mellitus. Results showed that effectiveness of curcumin on type 2 diabetes mellitus is due to it being anti-inflammatory, anti-oxidant, anti-hyperglycemic, anti-apoptotic, anti-hyperlipidemia and other activities. Numerous studies, including animal and clinical studies, have provided strong evidence to support curcumin’s crucial role in type 2 diabetes mellitus prevention due to its anti-inflammatory, anti-oxidant, antihyperglycemic, anti-apoptotic, antihyperlipidemic, and other actions. Curcumin interacts with a number of biomolecules, such as proteins, nucleic acids, membranes, through non-covalent and covalent binding. As stated above, curcumin exhibits good hypoglycemic action and is well taken at high dosages without adverse effects. It is therefore a potential approach for type 2 diabetes mellitus treatment or prevention. In light of these results, curcumin may be a promising prevention/treatment choice for type 2 diabetes mellitus.

Exploring the therapeutic mechanism of curcumin in prostate cancer using network pharmacology and molecular docking
Helyion | July 2024
Curcumin, a phenolic compound extracted from turmeric rhizomes, exhibits antitumour effects in preclinical models of tumours. We identified 307 key targets of curcumin in cancer treatment. Molecular docking experiments showed that the binding energies of curcumin to these core targets were all below −1.85 kJ mol−1, which fully demonstrated that curcumin could spontaneously bind to these core targets. Through in-depth network pharmacology and molecular docking studies, we have found that curcumin may have anticancer potential by upregulating the expression of PIK3R1 and STAT3, and downregulating the binding ability of molecules such as SRC, AKT1, HSP90AA1, ESR1, EGFR, HSP90AB1, MAPK8, and MAPK1. In addition, curcumin may interfere with the cyclic process of prostate cancer cells by inhibiting key signalling pathways such as the PI3K-Akt signalling pathway, MAPK signalling pathway, and Ras, thereby inhibiting their growth. This study not only reveals the potential molecular mechanism of curcumin in the treatment of prostate cancer but also provides an important theoretical basis for subsequent research. Curcumin exhibits multifaceted effects in prostate cancer treatment, including enhancing the sensitivity of prostate cancer to radiotherapy and chemotherapy, inhibiting cell proliferation, inducing cell death, inhibiting the expression of the PSA gene, decreasing the expression of androgen receptor, and decreasing the motility of tumour cells. In the present study, we systematically elucidated the possible mechanisms of action of curcumin in prostate cancer treatment by integrating network pharmacology and molecular docking. Curcumin acts on multiple targets and pathways involved in the treatment of prostate cancer.  Given that this study was conducted using relevant databases and the conclusions lacked experimental support, subsequent biological experiments, and evidence-based drug validation are required to ensure the reliability of the findings. In addition, we explored the molecular mechanism of action of curcumin in treating prostate cancer, providing a theoretical basis for the future development and clinical application of this traditional Chinese medicine.

Relationship of Curcumin with Aging and Alzheimer and Parkinson Disease, the Most Prevalent Age-Related Neurodegenerative Diseases: A Narrative Review
Nutrition Reviews | June 2024
One of the phytochemicals with diverse biological properties encompassing antioxidant, anti-inflammatory, antibacterial, antiviral, anticancer, antifungal, antidepressant, anti-allergic, and anti-aging properties is curcumin. Curcumin, a polyphenolic structure with a distinct orange hue and unique chemical properties, is derived from the roots of Curcuma longa, a member of the Zingiberaceae family, commonly known as turmeric. It has been noted that the incidence of neurodegenerative diseases is low in societies that consume curcumin widely.

Spices can boost energy levels and brain function
New York Post | June 2024
Turmeric is derived from the root of the Curcuma longa plant, a type of ginger. This root contains curcumin, a compound rich in anti-inflammatory and antioxidant properties. Known as the “gold” of the plant kingdom, turmeric also supports liver detoxification and serves as a natural pain killer. By reducing inflammation and oxidative damage, curcumin shields the brain from stressors that lead to cognitive decline. “Curcumin boosts levels of the brain hormone BDNF, which increases the growth of new neurons and fights various degenerative processes in the brain,” Crawford explained. In addition, and as The Post reported, turmeric has been shown to ease symptoms of indigestion, lower the risk of heart disease, fight depression, prevent cancer, improve memory, and lessen the pain from arthritis and other conditions.

Protective role of curcumin in high glucose-induced osteoblast dysfunctions via Nrf2 activation and ROS/JNK signaling inhibition
Authorea | June 2024
Curcumin is a polyphenolic phytochemical derived from the curcuma longa, and it exhibits anti-inflammatory and antioxidant properties, which associated with cell metabolism. The results showed that curcumin enhanced the osteoblast differentiation which are reduced by HG condition via Nrf2 activation and ROS/JNK inhibition. Knock-down of Nrf2 partially blocked curcumin-induced Nrf2 activation and ROS/JNK inhibition, as well as the attenuation of curcumin-induced osteoblast differentiation and survival in HG condition. JNK inhibition impair the positive effect of curcumin in response to HG, which presented a similar result to Nrf2 knock-down. Conclusion: ROS-related JNK phosphorylation might serve as the mechanism for HG-induced apoptosis and Nrf2 activation mediated by curcumin exerted a protective role against osteoblast apoptosis.

Effect of curcumin on gene expression of selected inflammatory markers in cortex and hippocampus of pilocarpine-induced seizure in rats on a routine exercise program
Comparative Clinical Pathology | June 2024
The combination of treadmill exercise program and curcumin administration has been shown to offer neuroprotection against epileptic seizure but without detailed mechanism of action being elucidated. This study therefore evaluated the responses of pro-inflammatory (tumor necrosis factor alpha [TNFα] and interleukin 6 [IL-6]) and anti-inflammatory (interleukin 10 [IL-10]) cytokines, as well as the transcription factor regulator (nuclear factor kappa B [NFκB]) gene expressions to combinatory therapy of curcumin and treadmill exercise in cortex and hippocampus of pilocarpine-induced epileptic seizure in rats. Treatment with either curcumin or curcumin plus exercise significantly ameliorated these impairments in the inflammatory markers ‘expression levels. Nevertheless, the combinatory therapy of curcumin and exercise showed significantly higher ameliorative effects in the cortical and hippocampal TNFα and IL-10, as well as cortical NFκB and IL-6. These superior therapeutic properties of the combination of curcumin and treadmill exercise further support the therapeutic potentials of this combinatory regimen in the management of epileptic seizures.

Emerging Anti-Inflammatory Attributes of Curcumin: A Novel Paradigm and Ameliorative Attributes for the Treatment of Osteoarthritis
Current Rheumatology Reviews | June 2024
Strong oxidant, curcumin, is diferuloyl methane; a member of the class of phenols known as curcuminoids that give Indian medicinal plants their characteristic turmeric-yellow hue. Over 5000 years ago, curcumin was first employed in the traditional Indian medical system. A growing amount of investigation reveals that curcumin has several pharmacological characteristics, including anticancer, hepatoprotective, anti-inflammatory, antioxidant, and antibacterial properties. Curcumin has been scientifically demonstrated to exhibit medicinal benefits for osteoarthritis (OA), and further research is being conducted on the numerous ways through which it suppresses inflammation and slows the progression of ailments. Clinical and preclinical studies suggest the potential efficacy of curcumin in managing osteoarthritis, warranting further investigation.

Mechanism of 5-fluorouracil induced resistance and role of piperine and curcumin as chemo-sensitizers in colon cancer
Naunyn-Schmiedeberg's Archives of Pharmacology | June 2024
Curcumin, a potent phytocompound derived from Curcuma longa, functions as a nuclear factor (NF)-κB inhibitor and sensitizer to numerous chemotherapeutic drugs. Piperine, an alkaloid found in Piper longum, inhibits cancer cell growth, causing cell cycle arrest and apoptosis. This review explores the mechanism of 5-FU-induced chemoresistance in colon cancer cells and the role of curcumin and piperine in enhancing the sensitivity of 5-FU-based chemotherapy.

Effects of curcumin in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis
Canadian Liver Journal | June 2024
Not only is curcumin vastly used in food as a spice, but it also has many therapeutic benefits, as it acts as an anti-inflammatory, antioxidant, anti-diabetic, anti-hyperlipidemia, immune-modulatory, reno-protective, anti-cancer, hepato-protective, hypoglycemic, antimicrobial, and anti-fibrotic. Curcumin treats NAFLD non-alcoholic fatty liver disease through a series of mechanisms. Firstly, it clears the liver cells from fat and decreases the synthesis of triglycerides by inhibiting the enzyme HMG COA reductase. Secondly, it increases the activation of cholesterol-7alpha-hydroxylase as well as reduces the absorption of cholesterol from the intestines. The hepato-protective activity of curcumin for the treatment of NAFLD has been evaluated in multiple clinical trials. Curcumin significantly reduced total glycerides and waist circumference compared with the placebo subgroup. It may become a promising agent in NAFLD non-alcoholic fatty liver disease treatment.

Curcuma longa: A Natural Ally in Alzheimer’s Disease Management
Curcumin and Neurodegenerative Diseases | June 2024
Curcuma longa contains a compound called curcumin that possesses potential biopharmacological activity. Curcumin is considered safe by the American Food and Drug Administration (FDA) and does not exhibit any side effects when consumed in moderate amounts. Numerous studies have been conducted on curcumin due to its therapeutic potential in various diseases, particularly in neurodegenerative disorders such as Alzheimer’s disease. Research indicates that this substance holds remarkable potential as an effective and safe treatment.

Patient-reported outcomes of curcumin supplementation in rheumatoid arthritis and psoriatic arthritis: a cross-sectional survey
Rheumatology International | June 2024
Pain scores decreased significantly after starting curcumin therapy. Patients who were taking curcumin for years reported better symptomatic control when compared with patients taking it for months (p 0.01), weeks (p 0.02), or days (p 0.02). There was a significant difference in symptom improvement in patients taking 200–1000 mg compared to patients taking less than 200 mg (p 0.01). Patients taking curcumin once or twice a day reported significant symptom improvement compared to patients taking it sporadically. Symptomatic improvement was reported as pain (35.7%), swelling (25%), stiffness (23.21%), and fatigue (16.07%). An interesting correlation exists between the symptom relief and the frequency, dosages (200–1000 mg), and duration (years) of curcumin supplementation. Our study indicates that curcumin supplementation positively influenced outcomes in 46.4% of individuals with rheumatoid arthritis and psoriatic arthritis, reducing pain, swelling, stiffness, and fatigue. This suggests curcumin’s potential as an adjunct therapy for these conditions.

Curcumin Inhibits the Progression of Non-small Cell Lung Cancer by Regulating DMRT3/SLC7A11 Axis
Molecular Biotechnology | June 2024
Emerging studies have shown that curcumin might repress non-small cell lung cancer progression by regulating ferroptosis. Curcumin blocked non-small cell lung cancer cell proliferation and angiopoiesis, and induced apoptosis and ferroptosis. DMRT3 or SLC7A11 upregulation partly abolished the suppressive role of curcumin on non-small cell lung cancer development. In mechanism, DMRT3 was a transcription factor of SLC7A11 and increased the transcription of SLC7A11 via binding to its promoter region. Curcumin inhibited non-small cell lung cancer growth in vivo by modulating DMRT3. Curcumin might constrain non-small cell lung cancer cell malignant phenotypes partly through the DMRT3/SLC7A11 axis, providing a promising therapeutic strategy for non-small cell lung cancer.

Curcumin, Piperine and Taurine Combination Enhances the Efficacy of Transarterial Chemoembolization Therapy in patients with Intermediate Stage Hepatocellular Carcinoma
Asian Pacific Journal of Cancer Prevention | June 2024
This study aimed to assess the effectiveness of curcumin (C), piperine (P) and taurine (T) combination as adjuvant agents on serum levels of IFN-γ, immunophenotypic and molecular characterization of mononuclear leukocytes (MNLs) in hepatocellular carcinoma patients treated with Transarterial chemoembolization (TACE). Patients and methods: Serum and MNLs were collected from 20 TACE-treated hepatocellular carcinoma patients before (baseline-control samples) and after treatment with 5 g curcumin capsules , 10 mg piperine and 0.5 mg taurine taken daily for three consecutive months. Immunophenotypic and molecular characterization of MNLs were determined by flow cytometry and quantitative real time PCR, respectively. In addition, serum IFN-γ level was quantified by ELISA. Results: After receiving treatment with  curcumin piperine T combination, there was a highly significant increase in IFN- γ levels in the sera of patients when compared to basal line control samples. Additionally, the group receiving combined therapy demonstrated a downregulation in the expression levels of PD-1, in MNLs as compared to controls. MNLs’ immunophenotyping revealed a significant decline in CD4+CD25+cells (regulatory T lymphocytes). Furthermore, clinicopathological characteristics revealed a highly significant impact of  curcumin piperine T combination on aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and alpha feto protein (AFP) levels. This study introduces a promising adjuvant  curcumin piperine T combined treatment as natural agents to enhance the management of hepatocellular carcinoma patients who are candidates to TACE treatment.

The effect of 8 weeks of HIIT training and Curcumin supplementation on Adiponectin levels and insulin resistance in obese women with type 2 diabetes
Journal of Sport and Biomotor Sciences | June 2024
Exercise intervention three sessions a week and daily curcumin consumption of 2100 mg in three meals was implemented for 8 weeks. Results: The interactive effect of curcumin and intense interval training increases adiponectin (P=0.001), decreases insulin resistance (P=0.001), decreases insulin (P=0.001), and significantly decreases glucose (P=0.002). Conclusion: The current research shows that performing intense intermittent exercises along with curcumin as a non-invasive method can have a positive and important effect on increasing adiponectin and reducing insulin resistance in patients with type 2 diabetes.

Epigenetic Orchestration of Neurodegenerative Disorders: A Possible Target for Curcumin as a Therapeutic
Neurochemical Research | June 2024
Studies have highlighted the marked antioxidant and neuroprotective abilities of polyphenols such as curcumin, by increased activity of detoxification systems like superoxide dismutase (SOD), catalase or glutathione peroxidase. The role of curcumin as an epigenetic modulator in neurological disorders and neuroinflammation apart from other chronic diseases have also been reported by a few groups. This review summarizes the current knowledge of the role of mitochondrial dysfunction, epigenetic modulations and mitoepigenetics in age-associated neurological disorders such as Alzheimer’s (AD), Parkinson’s (PD), Huntington’s disease (HD),  Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS), and describes the neuroprotective effects of curcumin in the treatment and/or prevention of these neurodegenerative diseases by regulation of the epigenetic machinery.

Effect of curcumin supplementation on symptoms of anxiety: A systematic review and meta-analysis of randomized controlled trials
Clinical Nutrition ESPEN | June 2024
Curcumin is a polyphenolic natural compound that has been used to treat various ailments such as symptoms of anxiety. A total of eight RCTs involving 567 participants were included in the analysis. A pooled analysis showed a significant effect of curcumin on anxiety symptoms (SMD: -1.56; 95% CI: -2.48, -0.64, p< 0.001; I2= 95.6%, p-heterogeneity< 0.001). Present meta-analysis demonstrated that curcumin intake might contribute to alleviation of anxiety disorder.

Turmeric: from spice to cure. A review of the anti-cancer, radioprotective and anti-inflammatory effects of turmeric sourced compounds
Frontiers in Nutrition | June 2024
Extensive research, encompassing preliminary, preclinical, and clinical studies, underscores the pharmacological significance of curcumin, the yellow pigment in turmeric. Its versatile properties include anti-inflammatory, immunomodulatory, antioxidant, hypolipidaemic, antimicrobial, anticarcinogenic, antitumor, radioprotective, neuroprotective, hepato-protective, nephroprotective, cardio-protective, and vasoprotective activities. Curcumin’s impact extends to various biochemical pathways, influencing molecular targets such as cytokines, transcription factors, kinases, growth factors, and microRNAs. ecognizing the valuable insights from traditional medicine in guiding natural product-based drug discovery, researchers explore the medicinal applications of turmeric across different traditional systems and investigate the modern pharmacological activities of curcumin, bridging the knowledge from ancient practices to current clinical trials. Through its antioxidant properties and the down-regulation of inflammatory targets, curcumin emerges as a promising agent in managing inflammatory skin diseases.In summary, our review has uncovered the multifaceted potential of curcumin both as an immunomodulator, as a radioprotective, anticancer medication and so much more. Curcumin boasts multiple benefits and presents itself as an interesting subject for future research.

Therapeutic Role of Turmeric in the Management of Periodontitis: A Comprehensive Review
Journal of Emerging Technologies and Innovative Research | June 2024
Curcumin stands out as a key bioactive compound, recognized for its distinctive yellow color and a wide range of beneficial biological effects. Curcumin has shown its prowess in fighting inflammation by slowing down the growth of inflammatory cells, curbing their spread, and inhibiting the formation of new blood vessels. Curcumin is like a versatile player on the chemical stage, boasting three highly reactive groups: one diketone and two phenolic groups. These features allow curcumin to engage in a range of chemical interactions that supercharge its effectiveness. From reversible and irreversible reactions to enzymatic processes and hydrogen transfers, curcumin can do it all, enhancing its potency. Moreover, it's not just about its own reactions—curcumin can also form sturdy bonds with both metals and nonmetals, acting as a reliable agent for complexing molecules. These unique traits make curcumin a valuable player in various biological roles, demonstrating its adaptability and impact.  The extensive body of research surrounding curcumin illuminates its remarkable anti-inflammatory properties, offering a beacon of hope in the fight against periodontal diseases. Through its ability to inhibit inflammatory cell proliferation, curb their spread, and disrupt blood vessel formation, curcumin presents a promising avenue for reducing inflammation associated with periodontitis.

The Effect of Curcumin on Oxidative Stress and Inflammatory Markers in Recreationally Active Women and Men
Virginia Polytechnic Institute and State University | June 2024
Curcumin, a bioactive compound found in turmeric, has been linked to antioxidant and anti-inflammatory properties. Curcumin, a compound found in turmeric, renowned for its antioxidant and anti-inflammatory properties, presents a potential avenue for managing oxidative stress and inflammation. This study assessed whether a four-week regimen of turmeric supplementation can attenuate markers of oxidative stress and inflammation in physically active individuals, 18 to 45 years of age. By investigating the potential antioxidant and anti-inflammatory properties of curcumin, this research aimed to contribute novel insights into strategies for mitigating oxidative stress and inflammation, thereby promoting health, well-being, and athletic performance.

Is Turmeric Beneficial To Diabetics? A Review By Nutrition Professionals
MSN.com | June 2024
Curcumin, a compound present in turmeric, has anti-inflammatory, antioxidant, anticancer and antimicrobial properties that help improve blood glucose levels. Another benefit is that it has cardioprotective, nephroprotective and hepatoprotective effects, which are organs that are at risk in the presence of the disease.Scientific evidence suggests that turmeric can help people with diabetes. According to research, turmeric helps control blood sugar levels, improve glucose sensitivity, and aid in weight loss.

Research progress on curcumin improving chronic low-grade inflammation and related diseases
Journal of Chinese Materia Medica | June 2024
Chronic low-grade inflammation(CLGI), a relatively new concept without a clear definition, refers to a nonspecific, chronic, continuous, and low-grade inflammation state, and it is closely associated with various chronic diseases, including obesity, inflammatory bowel disease, neurodegenerative diseases, and tumors. Improvement of CLGI can slow down disease progression. Anti-inflammatory treatment is an important strategy for prevention and treatment of CLGI. However, there is currently no definitive drug treatment method. Curcumin is a polyphenolic compound extracted from the rhizome of zingiberaceae, with significant anti-inflammatory activity. Research has shown that curcumin can play an anti-inflammatory role by regulating NF-κB, JAK/STAT, PI3K/Akt, MAPK, NLRP3 inflammasome, Nrf2/ARE, and other inflammation-related pathways. This paper summarized the anti-inflammatory mechanisms, pharmacological effect, and clinical application of curcumin in improving CLGI and other diseases, so as to provide a reference for in-depth research and clinical application of curcumin in improving CLGI.

Curcumin Alone and Combined With PI3K Inhibitors Elicits Positive Effects on Oropharyngeal Cancer Cell Lines
Anticancer Research | June 2024
Curcumin led to dose-dependent responses with reduced viability and proliferation; upon combining it with BYL719, additional positive effects were found for most OPSCC lines grown as monolayers, and these effects were validated in CU-OP-2 cells grown as spheroids. Curcumin with MK-1775 or PD-0332991 also elicited some positive effects on CU-OP-2 and CU-OP-17 cells. Curcumin alone led to dose-dependent responses and when combined with BYL719, positive effects were revealed, as they were when it was combined with MK-1775 or PD-0332991, suggesting a potential use of some of these combinations for HPV+ OPSCC.

Identification of Curcumin Targets in the Brain of Epileptic Mice Using DARTS
ACS Omega | June 2024
Curcumin, a compound derived from turmeric, is traditionally utilized in East Asian medicine for treating various health conditions, including epilepsy. Despite its involvement in numerous cellular signaling pathways, the specific mechanisms and targets of curcumin in epilepsy treatment have remained unclear. Our study focused on identifying the primary targets and functional pathways of curcumin in the brains of epileptic mice. Using drug affinity responsive target stabilization (DARTS) and affinity chromatography, we identified key targets in the mouse brain, revealing 232 and 70 potential curcumin targets, respectively. Bioinformatics analysis revealed a strong association of these proteins with focal adhesions and cytoskeletal components. Further experiments using DARTS, along with immunofluorescence staining and cell migration assays, confirmed curcumin’s ability to regulate the dynamics of focal adhesions and influence cell migration. This study not only advances our understanding of curcumin’s role in epilepsy treatment but also serves as a model for identifying therapeutic targets in neurological disorders. Curcumin, a plant polyphenol derived from the rhizomes of ginger family plants such as Curcuma longa, has been confirmed to have potential efficacy and safety in the treatment of epilepsy through multiple clinical studies. Notably, curcumin therapy does not interfere with the absorption, digestion, metabolism, or excretion of other antiepileptic drugs (such as sodium valproate, phenytoin, phenobarbital, and carbamazepine), and it can enhance their therapeutic effects while reducing the dosage and side effects.8 Currently, genomics-based drug repurposing techniques have identified curcumin as one of the most promising natural candidates for antiepileptic medication. Curcumin is a compound derived from turmeric, a plant that has been traditionally used to treat epilepsy. Our findings indicate that curcumin affects the cell migration and cytoskeleton through potential targets such as USP5, TNR, and CADPS.This system aims to identify potential targets for curcumin, a promising treatment for epilepsy. Our findings have revealed that USP5, CADPS, and TNR are the potential target proteins for curcumin.

Curcumin in the treatment of inflammation and oxidative stress responses in traumatic brain injury: a systematic review and meta-analysis
Frontiers in Neurology | June 2024
In our study, curcumin exhibits potent anti-inflammatory, antioxidant, and anti-apoptotic effects, suggesting its potential for treating TBI in humans. Curcumin, a neuroprotective agent, is relatively underexplored in TBI research, making our topic selection novel. Curcumin, an active compound extracted from the root of Curcuma longa, has demonstrated neuroprotective properties both in vitro and in vivo. Notably, it has shown potential in reducing oxidative stress and inflammation and enhancing redox balance. The analysis revealed that curcumin significantly reduced inflammatory cytokines across various concentrations, time points, and administration routes. Additionally, curcumin markedly enhanced the activity of oxidative stress markers while reducing MDA and oxyprotein levels. Furthermore, curcumin improved cerebral edema and upregulated neuroprotective factors like synapsin I, BDNF, and CREB, without reducing mNSS. About autophagy and apoptosis, curcumin increased the activity of Beclin-1and Bcl-2, while decreasing caspase-3, the apoptosis index, and P62.  Curcumin supplementation positively affects traumatic brain injury (TBI) by alleviating oxidative stress and inflammatory responses and promoting neuroprotection. It holds potential as a therapeutic agent for human TBI.

The Role of Curcumin in Oral Health and Diseases: A Systematic Review
Antioxidants | May 2024
Curcumin is a prominent natural compound that has been extensively studied in the recent literature due to its anti-inflammatory, antioxidant, antibacterial, and anticancer activities. Since ancient times, curcumin has been recognized for its multiple therapeutic properties, which have been confirmed by recent clinical studies. Recent scientific research on curcumin has demonstrated that it possesses the following properties: anti-inflammatory, antioxidant, antifungal, antidepressant, healing (therapeutic in Crohn’s disease, ulcerative colitis, and peptic and gastric ulcers), and as an adjuvant in acute coronary syndrome therapies, chemotherapies, and as a hypoglycemic. Curcumin also stands out for its ability to positively influence intestinal microbiota, thereby contributing to maintaining an optimal microbial balance. This effect can have significant implications in the prevention and treatment of gastrointestinal disorders, thereby enhancing overall health. Additionally, recent studies have highlighted curcumin has potential in supporting brain health and cognitive function, opening intriguing avenues in the treatment of neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases. Curcumin also protects against risk factors such as smoking, alcohol, and stress, The ascertained pleiotropic nature of curcumin creates interference in complex biological processes and various inflammatory factors that regulate oxidation–reduction processes, such as reactive oxygen species (ROS), cytokines, cyclooxygenase-2 (COX-2), interleukins (ILs), nuclear factor kappa B (NF-κB), C-reactive proteins, transforming growth factor-β (TGF-β), and other enzymes involved in inflammation. Curcumin inhibits vascular endothelial growth factor (VEGF) and various kinases, demonstrating a controlling action in angiogenesis and the growth of cancerous lesions. Due to its medicinal and pharmacological properties, curcumin has also found application in the treatment of multiple diseases of the oral cavity (caries, periodontitis, gingivitis, aphthous stomatitis, oral candidiasis, mucositis, oral submucosal fibrosis, lichen planus, oral leukoplakia, carcinogenic lesions, etc.), which affect approximately 3.5 billion people worldwide.

The regulating effect of curcumin on NF-κB pathway in neurodegenerative diseases: a review of the underlying mechanisms
Inflammopharmacology | May 2024
Curcumin has been noted to be a popular anti-oxidant and anti-inflammatory substance and is the foremost natural compound produced by turmeric. According to various studies, when playing an anti-inflammatory role, it interacts with several modulating proteins of long-standing disease signaling pathways and has an unprovocative consequence on pro-inflammatory cytokines. This review article determined to figure out curcumin’s role in limiting the promotion of neurodegenerative disease via influencing the NF-κB signaling route. Preclinical studies were gathered from plenty of scientific platforms including PubMed, Scopus, Cochrane, and Google Scholar to evaluate this hypothesis. Extracted findings from the literature review explained the repressing impact of Curcumin on the NF-κB signaling pathway and, occasionally down-regulating the cytokine expression.

Antiviral, anti-inflammatory and antioxidant effects of curcumin and curcuminoids in SH-SY5Y cells infected by SARS-CoV-2
Nature | May 2024
Curcumin, a natural spice, has garnered significant attention for its potential in treating conditions characterized by immune system perturbations and inflammatory responses, including COVID-19. CUR and other curcuminoids are the primary bioactive components of turmeric (Curcuma longa), a substance that has been employed in the traditional medicine practices of diverse cultures for centuries. This enduring use is attributed to the anti-inflammatory, antioxidant, antibacterial, antiviral and neuroprotective properties exhibited by curcuminoids. Furthermore, curcuminoids can play a role in inhibiting certain enzymes associated with the inflammatory process, such as mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinases (JNK), and nuclear factor kappa B (NF-kB). The antioxidant properties of curcuminoids have been shown to inhibit carcinogenic reactive oxygen species (ROS), including superoxide anions, hydroxyl radicals, nitrites, and peroxides. Curcumin can stimulate both the activation of antioxidant enzymes and the decrease in expression of pro-inflammatory cytokines. A recent systematic review identified six studies demonstrating that curcumin supplementation led to a significant decrease in common COVID-19 symptoms, reduced hospitalization duration, and decreased mortality rates. The authors concluded that curcumin treatment mitigates the manifestation of cytokine storms by reducing pro-inflammatory factors and activating anti-inflammatory pathways. They further suggested that curcumin treatment may alleviate COVID-19 symptoms by restoring the balance between pro-inflammatory and anti-inflammatory responses.

Curcumin Promotes the Proliferation, Migration, and Angiogenesis of HUVECs to Improve Atherosclerosis through the Wnt/β-Catenin Pathway
Journal of Biological Regulators and Homeostatic Agents | May 2024
Curcumin treatment significantly alleviated ox-LDL-induced HUVECs injury, as evidenced by elevating the proliferative ability, cell migration, and angiogenesis. Moreover, the Wnt/β-catenin pathway was substantially boosted following ox-LDL treatment, which was suppressed by curcumin. The inhibitory effects of curcumin treatment on the Wnt/β-catenin signaling pathway were reduced by SKL2001. Furthermore, the promoting effects of curcumin on ox-LDL-induced cell damage were hampered following SKL2001 treatment in HUVECs (p < 0.05). Conclusion: Curcumin elevated cell proliferation, migration, and angiogenesis of HUVECs to inhibit the development of atherosclerosis through inactivating the Wnt/β-catenin pathway.

The Impact of Curcumin, Resveratrol, and Cinnamon on Modulating Oxidative Stress and Antioxidant Activity in Type 2 Diabetes: Moving beyond an Anti-Hyperglycaemic Evaluation
Antioxidants | May 2024
Curcumin is an active chemical compound present in the rhizome of the plant Curcuma longa, also known as turmeric. It exhibits antioxidant, anti-inflammatory, antimicrobial, anticancer, anti-rheumatic, immunomodulatory, anti-hyperglycaemic, and cardio-renal-hepato-protective properties. In one animal study, curcumin and its analogues were shown to have a similar mechanism of action to thiazolidinedione, an antidiabetic drug, through the activation of the peroxisome proliferator-activated receptor gamma (PPAR-γ), suggesting that curcumin may be effective in regulating glycaemia and lipid levels. Curcumin appears to have beneficial effects in reducing fasting glucose, glycated haemoglobin (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), and TNF-α. It also positively influences lipid metabolism by lowering low-density lipoprotein (LDL) cholesterol and triglyceride levels while increasing high-density lipoprotein (HDL) cholesterol. Curcumin demonstrates beneficial effects not only on the glycaemic control but also on anthropometric parameters. Hodaei et al. recruited 53 individuals with excess body weight and T2DM. After 10 weeks of supplementation, the study group showed a significant decrease in body weight, body mass index (BMI), waist circumference, and blood glucose levels (p < 0.05) compared to the control group. Jiménez-Osorio et al investigated the impact of curcumin supplementation on markers of oxidative stress, antioxidant enzyme activity, and nuclear factor erythroid 2-related factor 2 (Nrf2) activation. In individuals with non-diabetic proteinuria and CKD, curcumin attenuated lipid peroxidation, whereas curcumin increased antioxidant capacity in individuals with T2DM and CKD with proteinuria. These results suggest a potential reduction in oxidative stress in patients with diabetes and CKD. Patients with T2DM and CKD (n = 14) received 500 mg/day of curcumin for 15 days (30 days in patients with overt proteinuria). Curcumin supplementation significantly reduced urinary microalbumin excretion and lowered serum MDA levels by enhancing the specifically Nrf2-regulated protein, NAD(P)H quinone oxidoreductase 1 (NQO-1), along with other antioxidant enzymes in the lymphocytes. Additionally, patients showed reduced serum lipopolysaccharide (LPS) content and increased inhibitor of nuclear factor kappa-B kinase (IκB kinase) proteins inhibiting inflammatory signalling in lymphocytes. Interestingly, curcumin stimulated the activity of several gut bacteria crucial for maintaining the integrity and functioning of the gut barrier. In summary, short-term curcumin intervention inhibits the progression of DKD by activating the Nrf2 antioxidant system and exerting anti-inflammatory effects in patients with T2DM. Aerobic training + curcumin supplementation group showed the best results with significantly reduced MDA and hs-CRP levels and increased glutathione and TAC compared to the aerobic-training and curcumin-supplementation-alone, respectively. These results demonstrate the positive effects of curcumin supplementation and physical activity on the metabolic state, oxidative stress markers, and hs-CRP. Curcumin supplementation appears to have beneficial effects in individuals with T2DM and coronary heart disease. Shafabakhsh et al. recruited 60 patients with T2DM and CHD aged 45–85 and were randomly assigned to two groups—the experimental group receiving 1000 mg/day of curcumin and the control group receiving a placebo for 12 weeks. After the intervention, the experimental group showed a significant reduction in MDA levels and a significant increase in TAC and GSH levels compared to those of the placebo group. Additionally, curcumin consumption increased the level of peroxisome proliferator-activated receptor gamma (PPAR-γ). Na et al. investigated whether curcumin supplementation reduced A-FABP levels. The curcumin-receiving group had significantly reduced serum A-FABP levels, CRP, TNF-α, and IL-6compared to the placebo one. Additionally, curcumin supplementation also significantly increased the activity of superoxide dismutase (SOD) in serum. The researchers concluded that curcumin may have antidiabetic effects by reducing A-FABP levels in serum. Curcumin also exhibits lipid-metabolism-lowering effects. Forty-four individuals with T2DM were randomly assigned to a group supplementing with curcumin at a dose of 1500 mg/day or to a control group receiving a placebo for 10 weeks. In the curcumin-supplementing group, the average hs-CRP concentration significantly decreased, and the average adiponectin concentration significantly increased compared to in the placebo group. These results suggest that curcumin intake may reduce diabetic complications by decreasing TG levels and inflammatory markers.

Unraveling the protective effects of curcumin against drugs of abuse
Cell | May 2024
Curcumin, a natural compound derived from the turmeric plant (Curcuma longa), has garnered significant attention for its diverse neuroprotective properties. Curcumin has been widely recognized for its remarkable anti-inflammatory, antioxidant, and anti-apoptotic effects, which have shown great potential in the treatment of various disorders, encompassing psychiatric and neurodegenerative diseases. Overall, curcumin demonstrates promising effects against the neurotoxicity induced by abused drugs through a wide range of mechanisms; modulation of inflammatory cytokines, maintenance of ion homeostasis, epigenetic regulation, enhancement of antioxidant capacity, as well as the activation of the cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) signaling pathways. Curcumin has demonstrated its viability as a potential therapeutic option for cancer treatment by selectively targeting diverse cell signaling pathways encompassing growth factors, cytokines, transcription factors, and genes that regulate cellular proliferation and apoptosis. Curcumin has been shown to be effective in treating outcomes linked to obesity through promoting the expression of antioxidants and directly slowing preadipocyte development. Studies have demonstrated the possible benefits of curcumin in chronic obstructive pulmonary disease (COPD), through attenuation of airway inflammation and remodeling. Moreover, the relaxant effects of curcumin on tracheal smooth muscle indicate its bronchodilatory properties, suggesting its potential advantage in the treatment of diverse respiratory and allergic disorders. This evidence supports its ability to promote crucial aspects of wound healing, such as collagen deposition, granulation tissue formation, tissue remodeling, and wound contraction. Another potential mechanism of action of curcumin on depressive symptoms is linked to the inhibition of transcription signaling pathways of some nuclear factors, including nuclear factor kappa B, which is necessary for the production of pro-inflammatory cytokines and is consequently involved in the pathogenesis of neuroinflammation. Furthermore, curcumin has been shown to boost levels of brain-derived neurotrophic factor (BDNF), a neurotrophin linked to the etiology of depression. In addition to its therapeutic effects on depressive disorders, curcumin has exhibited potential as a therapeutic intervention for delusional disorders. These findings suggest that curcumin emerges as a promising therapeutic agent in combatting the detrimental effects induced by drugs of abuse. Curcumin has demonstrated the ability to attenuate neuronal damage, oxidative stress, inflammation, and apoptosis induced by these addictive substances. The findings presented in this review highlight the potential of curcumin as a multifaceted neuroprotective agent in the context of drug addiction. By targeting key pathological pathways associated with drug-induced neurotoxicity, curcumin holds great promise for the prevention and treatment of addiction-related cognitive impairments and neurodegenerative disorders. Furthermore, the ability of curcumin to modulate neuroplasticity and synaptic plasticity provides a rationale for its use in promoting neuronal recovery and functional restoration following chronic drug exposure.

Curcumin in the treatment of inflammation and oxidative stress responses in traumatic brain injury: a systematic review and meta-analysis
Frontiers in Neurology | May 2024
Curcumin, an active compound extracted from the root of Curcuma longa, has demonstrated neuroprotective properties both in vitro and in vivo. Notably, it has shown potential in reducing oxidative stress and inflammation and enhancing redox balance. Curcumin supplementation positively affects traumatic brain injury by alleviating oxidative stress and inflammatory responses and promoting neuroprotection. It holds potential as a therapeutic agent for human traumatic brain injury.  Curcumin significantly mitigates the effects of inflammatory cytokines such as IL-1β, IL-6, and TNF-α. Moreover, curcumin enhances the efficacy of oxidative stress factors, including SOD, Sir2, GPx, and Nrf2. Regarding neurological function, curcumin reduces brain edema, increases neuron survival rates and augmentation. Furthermore, curcumin enhances the effects of Beclin-1 and Bcl-2 in autophagy and apoptosis. Curcumin, administered in various concentrations, durations, and routes, significantly reduces pro-inflammatory cytokines in the experimental group, improves nerve function following TBI, and mitigates the inflammatory response. Bassani et al. demonstrated that curcumin effectively reduces neuroinflammation in models of neurodegenerative and neuroinflammatory diseases. Additional studies conducted in animal experimental models have shown that curcumin inhibits the TLR4/NF-κB signaling pathway, thereby down-regulating inflammatory cytokines. The results of this meta-analysis confirm that curcumin effectively reduces oxidative stress levels following TBI. Curcumin, a widely used antioxidant with neuroprotective properties, has been shown to inhibit lipid peroxide formation in the presence of lipid peroxidation-inducing drugs. Moreover, curcumin reduces levels of MDA, 4-HNE, and protein carbonyls, restores mitochondrial oxidation function, stabilizes cell membrane homeostasis, and thereby mitigates the oxidative stress response following TBI. Gao et al. demonstrated that curcumin treatment significantly reduces MDA levels and induces GPx activation, thereby ameliorating TBI-induced oxidative stress in rat models. Studies provide evidence that curcumin is a potent activator of Nrf2 both in vivo and in vitro, enhancing Nrf2 activation in the brain.

Curcumin exerts anti-inflammatory, antioxidant and anti-ferroptotic effects through the Nrf2/HO-1 pathway to protect cardiomyocytes against sepsis
Signa Vitae | May 2024
The results show that curcumin significantly improved cell viability in lipopolysaccharide (LPS)-induced H9c2 cells (p < 0.01). Curcumin also significantly reduced inflammatory factor levels in LPS-induced cardiomyocytes (p < 0.001). Curcumin down-regulated ROS and MDA levels (p < 0.001), and up-regulated SOD and GSH levels (p < 0.001). A decrease in both Fe2+ content and protein expression of ACSL4 (p < 0.001), and increased protein expression of glutathione peroxidase 4 (GPX4) (p < 0.001) were observed with curcumin. By knocking down Nrf2 curcumin’s therapeutic effect against LPS was eliminated. So curcumin can inhibit LPS-induced oxidative stress, inflammation and ferroptosis in cardiomyocytes by regulating Nrf-2/HO-1 signaling.

The Role of Curcumin in Cancer: A Focus on the PI3K/Akt Pathway
Cancers | May 2024
Curcumin is a polyphenol isolated from the rhizomes of Curcuma longa and has been widely studied for its anti-inflammatory, anti-oxidant, and anti-cancer effects. Curcumin acts on the regulation of different aspects of cancer development, including initiation, metastasis, angiogenesis, and progression. The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathway is a key target in cancer therapy, since it is implicated in initiation, proliferation, and cancer cell survival. Curcumin has been found to inhibit the PI3K/Akt pathway in tumor cells, primarily via the regulation of different key mediators, including growth factors, protein kinases, and cytokines. This review presents the therapeutic potential of curcumin in different malignancies, such as glioblastoma, prostate and breast cancer, and head and neck cancers, through the targeting of the PI3K/Akt signaling pathway. This review focuses on the multifaceted role of curcumin in improving different malignancies, primarily through the regulation of the PI3K/Akt signaling pathway. From a biological point of view, this structural property of curcumin has been widely studied in diseases such as arthritis and Alzheimer’s disease. Moreover, the presence of the diketone group, along with the two phenolic groups, allows curcumin to take part in different reactions in which electron transfer and hydrogen abstraction are involved. This is particularly useful in the case of reactions with free radicals. Curcumin’s reaction with reactive oxygen species (ROSs) results in the formation of curcumin–phenoxyl radicals that are more stable and less reactive than the initial free forms. Interestingly, the stabilization of superoxide radicals by curcumin has been considered equally efficient to the effects of key antioxidants, such as superoxide dismutase.

Curcumin attenuates brain aging by reducing apoptosis and oxidative stress
Metabolic Brain Disease | May 2024
Curcumin, exerts its neuroprotective and anti-aging effects in the aged brain. Curcumin is a natural antioxidant with potent anti-aging and neuroprotective properties. Our results indicated that treatment with curcumin in aged rats attenuates brain lipid peroxidation, which was accompanied by a significant increase in the BDNF, VEGF, superoxide dismutase (SOD) activity, and anti-apoptotic protein BCl-2. The study indicates that curcumin could alleviate brain aging which may be due to attenuating oxidative stress, inhibiting apoptosis, and up-regulating SOD activity, which in turn enhances VEGF and BDNF. Therefore, curcumin has potential therapeutic value in the treatment of neurological apoptosis, neurogenesis, and angiogenesis changes caused by brain aging.

Effect of Curcumin plus Piperine on Redox Imbalance and Inflammation in Inflammatory Bowel Disease Patients: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Preprints | May 2024
Curcumin, a hydrophobic polyphenol, exhibits potent antioxidant, anti-inflammatory, antitumor, antimicrobial, anti-glycating, anti-coagulant and healing properties, as evidenced by both experimental studies and clinical trials clinical trials in IBD and other clinical situations such as Type 2 diabetes and some cancers. Our findings allow to affirm that the standard commercially available powder, rich in curcumin and combined with piperine, exhibits significant antioxidant action by substantially enhancing the endogenous defense mechanism, as evidenced by a noteworthy increase in serum SOD superoxide dismutas levels among supplemented patients over the three-month intervention period. These unprecedented results for this polyphenol underscore its beneficial effects on patients with IBD. Results are corroborated by a randomized clinical trial in patients with metabolic syndrome, where the combination of curcumin plus piperine, supplemented at the same dosage used daily in this study (1000 mg + 10 mg), for 8 weeks, significantly increased SOD superoxide dismutas activity. Another study conducted by Panahi et al. also demonstrated the effectiveness of curcumin in increasing SOD activity in patients with osteoarthritis after 6 weeks thus demonstrating the effectiveness of curcumin on this marker. of redox imbalance. The observed increase in SOD levels in this study among patients receiving curcumin plus piperine, with no alterations in H2O2 and MDA levels, suggests a beneficial effect of this supplementation.

Curcumin prevents high glucose-induced stimulatory effects of renal cell secretome on fibroblast activation via mitigating intracellular free radicals and TGF-β secretion
Biomedicine & Pharmacotherapy | May 2024
All the effects of high glucose were successfully mitigated by curcumin. Curcumin prevents the high glucose-induced stimulatory effects of renal cell secretome on fibroblast activation, at least in part, via mitigating intracellular ROS and TGF-β secretion. In kidney stone mice and H2O2-exposed macrophages, curcumin has been demonstrated to hamper oxidative stress by elevating glutathione production and antioxidant enzyme activity. Additionally, curcumin has been reported with an anti-fibrotic property to attenuate renal fibrosis induced by kidney stone disease and ischemia/reperfusion injury in mice accompanied by the reduction of α-smooth muscle actin (α-SMA), collagen I, and fibronectin expression. Curcumin has multiple health benefits due to its anti-diabetic, anti-oxidative and anti-inflammatory effects. Particularly in chronic kidney disease (CKD), recent randomized controlled trials have reported that curcumin can reduce oxidative stress as recognized by a decrease in malondialdehyde (an oxidative stress marker) and an increase in catalase (an antioxidant) in the plasma of CKD patients undergoing hemodialysis and peritoneal dialysis. Furthermore, curcumin supplementation for 12 weeks can suppress inflammatory processes in hemodialysis patients as shown by reduced expression of NF-κB in peripheral blood mononuclear cells and decreased plasma levels of pro-inflammatory cytokines (IL-6 and TNF-α).

A role for curcumin in preventing liver fibrosis in animal: A systematic review and meta-analysis
Frontiers in Pharmacology | May 2024
Curcumin therapy improved fibrosis degree, oxidative stress level, inflammation level, and liver synthesis function in animal models of liver fibrosis. Curcumin intervention not only mitigates liver fibrosis but also enhances liver function, while concurrently modulating inflammatory responses and antioxidant capacity in animal models. This result provided a strong basis for further large-scale animal studies as well as clinical trials in humans in the future. Numerous studies demonstrated that curcumin effectively targets the inhibition of HSC activation (Shu et al., 2023).  Curcumin could inhibit activity and promote apoptosis in LX-2 cells by suppressing autophagy through activation of the PI3K/Akt/mTOR signaling pathway (Shu et al., 2023). Lian et al. discovered that curcumin inhibits glycolysis and regulates metabolism in HSCs by modulating hedgehog signaling (Lian et al., 2015). Qin et al., in their intervention with curcumin on HSC-T6 cells, found that curcumin could protect against activation and migration of hepatic stellate cells by inhibiting the CXCL12/CXCR4 biological axis in liver fibrosis (Qin et al., 2018). Research indicates that curcumin reduces serum cholesterol levels by increasing hepatic LDL receptor expression, inhibiting LDL oxidation, and enhancing bile acid secretion and faecal cholesterol excretion (Zhang et al., 2019). Curcumin also suppresses genes involved in cholesterol biosynthesis, proecting against liver injury and fibrogenesis in animal models (Fu et al., 2008; Peschel et al., 2007). Curcumin, a hydrophobic polyphenol extracted from the rhizome of Curcuma longa, is widely utilized in the treatment of cardiovascular diseases, liver diseases, and tumours (Xu et al., 2020; Jabczyk et al., 2021; Pourbagher-Shahri et al., 2021). Clinical and basic studies have confirmed its remarkable pharmacological efficacy in treating liver diseases like NAFLD, liver fibrosis, and liver cancer (Nelson et al., 2017; Farzaei et al., 2018); (E. S. Lee et al., 2020) Our meta-analysis showcased curcumin’s effectiveness in preclinical liver fibrosis studies. The potential protective mechanisms observed in animals encompass liver protection, collagen production inhibition, oxidative stress reduction, and inflammatory response regulation.

Curcumin alleviates myocardial inflammation, apoptosis, and oxidative stress induced by acute pulmonary embolism
Journal of Physiology and Pharmacology | May 2024
Curcumin is a substance extracted from the roots of the turmeric plant and is a lipophilic polyphenol that acts as an antibiotic, anti-inflammatory, and anti-aging agent. Curcumin has significant tumor suppressor potential in a variety of cancers by inhibiting cancer cell proliferation, metastasis, cell cycle entry, or anti-apoptosis. Studies have determined that curcumin is beneficial in regulating oxidative stress, inflammation, and apoptosis in cardiovascular diseases. It has been described that curcumin inhibits lung injury and inflammation in APE by microRNA- 21/phosphatase and tensin homologue (PTEN) axis and nuclear factor kappaB (NF-kB) pathway. In addition, curcumin ameliorates oxidative stress and inhibits apoptosis in diabetic cardiomyopathy. Moreover, it can reduce the production of pro-inflammatory cytokines and alleviate myocardial injury. It has been validated that curcumin has a protective effect on cardiomyocytes by mediating oxidative stress and apoptotic pathways. Curcumin acts against coronary microembolization-induced myocardial damage by which the mechanism is related to reducing myocardial apoptosis and inhibiting inflammation. The protective effects of curcumin on cardiovascular diseases have been extensively elucidated. Curcumin restores biochemical indices, maintains antioxidant capacity, and reduces pro-inflammatory cytokine in diabetes-induced myocardial infarction. Consistent with these study findings, our research discovered that curcumin pretreatment recovered pathological changes in myocardial tissue and reduced apoptosis, inflammatory responses, and oxidative stress by altering relevant indicators. Protective efficacy against cardiovascular diseases by curcumin, a common natural polyphenolic compound, which has antithrombotic properties and reduces platelet accumulation in the circulation by inhibiting thromboxane synthesis has been demonstrated. Curcumin improved APE-induced myocardial injury, reduced myocardial tissue edema, and thrombus volume. It attenuated APE-induced myocardial inflammation and apoptosis, as well as reduced lung injury and pulmonary artery pressure. Curcumin promoted microRNA-145-5p expression in APE rat myocardium. In conclusion, curcumin alleviates myocardial inflammation, apoptosis, and oxidative stress induced by APE by regulating microRNA-145-5p/IRS1 axis.

Investigation of Antibacterial Activity of Curcumin and Synergistic Effect with Gentamicin Sulfate
Namık Kemal University | May 2024
Curcumin is a food spice that is a natural component of Curcuma longa  rhizomes. It has been widely used as a medicine in the treatment of various diseases in Asian and Middle Eastern countries for years. Curcumin, also known as turmeric, has been shown to have antibacterial, antifungal, antiviral, antioxidant, anti-inflammatory and anticancer activities. In the society, it is known to be used for therapeutic purposes against various malignant diseases, diabetes, arthritis, gastritis, urinary tract infections, skin diseases and other chronic diseases. Studies have shown that combinations of curcumin with different agents, including various antibiotics, have synergistic effects against bacteria. Curcumin is a natural agent whose therapeutic effects have been investigated due to its various biological and medicinal properties. In this study investigating the antibacterial activity of curcumin on some standard strains, it was found that curcumin showed antibacterial activity at a concentration of 62.5 µg/mL against all tested bacteria except E. faecalis (7.81 µg/mL). The results of this study and similar studies also emphasize the antibacterial activity of curcumin. In a study by Ungphaiboon et al. , in which they investigated the antibacterial activity of curcumin extracts obtained from Curcuma longa L. rhizomes on various microorganisms, they found the MIC values of curcumin as 16 and 128 µg/mL for Bacillus subtilis NCTC 10073 and S. aureus ATCC 25923, respectively. This study shows that curcumin alone or in combination with gentamicin sulfate has antimicrobial activity.

Curcumin inhibits colorectal cancer development by blocking the YAP/TAZ signaling axis
Biocell | May 2024
Curcumin is a plant polyphenol with antitumor properties and inhibits the development of colorectal cancer. In our study, we proved that curcumin significantly inhibited the colorectal cancer cell viability, cell migration, and cell invasion abilities. In addition, curcumin inhibited YAP and Transcriptional coactivator with TAZ or the YAP/TAZ signaling axis in colorectal cancer cells. Further, in the nude mice model, curcumin treatment significantly decreased the size and weight of xenotransplant tumors. Therefore, curcumin significantly inhibited colorectal cancer development and invasion by regulating the YAP/TAZ signaling axis. Curcumin has documented various properties on tumor cells, including anti-proliferative, anti-inflammatory, and antioxidant activities. Studies have shown that curcumin could effectively inhibit the invasion and proliferation of human cancers, such as Wilms tumor (WT), esophageal cancer, and colorectal cancer . Further, curcumin inhibits the occurrence and development of colorectal cancer mainly through anti-inflammatory mechanisms and anti-tumor-related pathways. Previous studies have shown that curcumin has an inhibitory effect on colorectal cancer. Our experimental results that curcumin inhibited the cell viability, migration, and invasion of colorectal cancer in a dose-dependent manner are also consistent with such reports. In conclusion, this study demonstrates that curcumin inhibits the YAP/TAZ signaling pathway by promoting YAP phosphorylation and ultimately inhibits colorectal cancer tumorigenesis. Our study also further clarified the mechanism of curcumin in the treatment of colorectal cancer, laying an experimental and theoretical basis for further elucidation of the mechanism of curcumin in colorectal cancer treatment. This finding has promising significance for promoting the application of curcumin for treating colorectal cancer.

Therapeutic Potentials Of Curcumin Against Neurodegenerative Diseases: A Review
International Journal Of Research and Analytical Reviews | May 2024
Curcumin, a polyphenolic compound found in turmeric, has gained attention for its potential neuroprotective properties. It has long been utilized as a medical herb and culinary spice in Asian countries for a range of illnesses. This review centers on the latest developments and the underlying processes of curcumin's numerous natural benefits against neurodegenerative diseases, including Parkinson's disease. The current research indicates that the diagnosis of major depressive disorder is related to both the neuroprotective benefits of antidepressants and cellular shrinkage and the death of neurons. The neuroprotection of curcumin against Parkinson's disease and Alzheimer's disease is primarily attributed to its anti-inflammatory and antioxidant properties. In addition, according to reports curcumin improves striatal TH survival filaments additionally, pars compacta (SNPC) neurons, reduces aberrant turning geste, and exerts neuroprotective effects, at least partially, through a 7-nAChR-mediated medium. In multiple sclerosis (MS), an important part of the immune system is inflammation that leads to the damage seen in the CNS. Curcumin inhibits T cell, and IL-12 signaling and may be used to treat MS and other inflammatory conditions. Curcumin’s anti-inflammatory, anticancer, and antibacterial qualities have been the subject of numerous both in vitro and in vivo investigations, both of its own and in conjunction with conventional therapies. Studies on epidemiology have shown that cultures with high curcumin consumption have lower rates of disorders affecting inflammatory and memory retention, such as Alzheimer's illness. Curcumin has been utilized and additionally proposed is a possible preventive measure against Parkinson's disorder since studies have indicated that curcumin-consuming Indian communities do not exhibit age-related alterations in their neural neurons that produce dopamine. Furthermore, as will be covered in more information below, a multitude of both vivo and in vitro investigations offer strong proof that curcumin protects against Parkinson's disease-like symptoms. In conclusion, the neuroprotective effect of curcumin on neurodegenerative diseases holds significant promise based on the comprehensive body of research conducted thus far. Through its multifaceted mechanisms of action including antioxidant, anti- inflammatory, and anti-amyloid properties, curcumin demonstrates the potential to mitigate neurodegenerative processes associated with conditions such as Depression, Alzheimer's disease, Parkinson's disease, and multiple sclerosis. The studies reviewed consistently indicate that curcumin possesses the ability to modulate key cellular pathways involved in neuroprotection, thereby attenuating neuronal damage and improving cognitive function in various experimental models. The existing evidence underscores curcumin as a promising natural compound worthy of continued exploration for the development of novel therapeutic strategies against neurodegenerative diseases.

Patient-reported outcomes of curcumin supplementation in rheumatoid arthritis and psoriatic arthritis: a cross-sectional survey
Rheumatology International | April 2024
Pain scores decreased significantly after starting curcumin therapy. Patients who were taking curcumin for years reported better symptomatic control when compared with patients taking it for months, weeks, or days. There was a significant difference in symptom improvement in patients taking 200–1000 mg compared to patients taking less than 200 mg. Patients taking curcumin once or twice a day reported significant symptom improvement compared to patients taking it sporadically. An interesting correlation exists between the symptom relief and the frequency, dosages (200–1000 mg), and duration (years) of curcumin supplementation. Our study indicates that curcumin supplementation positively influenced outcomes in 46.4% of individuals with rheumatoid arthritis and psoriatic arthritis, reducing pain, swelling, stiffness, and fatigue. Curcumin is suggested to possess potent anti-inflammatory properties. This suggests curcumin’s potential as an adjunct therapy for these conditions.

Curcumin Inhibits α-Synuclein Aggregation by Acting on Liquid–Liquid Phase Transition
Food | April 2024
Parkinson’s disease, the second most common neurodegenerative disorder, is linked to α-synuclein (α-Syn) aggregation. Curcumin can inhibit amyloid formation by inhibiting the occurrence of LLPS and the subsequent formation of oligomers of α-Syn in the early stages of aggregation. These results may help to clarify the mechanism by which curcumin inhibits the formation of α-Syn aggregates during the development of Parkinson’s disease. Curcumin, the main polyphenolic substance present in the rhizomes of Curcuma longa L., has been shown to interact with amyloid-β peptide and α-Syn, thus inhibiting their aggregation, deposition, and neurotoxicity. Importantly, curcumin has also been recognized for its pharmacological benefits in a multitude of pathological contexts, including diabetes, cancer, and even neurodegenerative diseases. We found that curcumin could inhibit the formation of α-Syn oligomers by affecting the initial phase transition of α-Syn in the condensation pathway through direct interaction with droplets.

Neuroprotective and anti-inflammatory effects of curcumin in Alzheimer's disease: Targeting neuroinflammation strategies
Phytotherapy Research | April 2024
Curcumin, a polyphenolic compound derived from Curcuma longa, has shown potential neuroprotective effects due to its anti-inflammatory and antioxidant properties. An exhaustive literature search was conducted, focusing on recent studies within the last 10 years related to curcumin's impact on neuroinflammation and its neuroprotective role in Alzheimer's disease. The review methodology included sourcing articles from specialized databases using specific medical subject headings terms to ensure precision and relevance. Curcumin demonstrates significant neuroprotective properties by modulating neuroinflammatory pathways, scavenging reactive oxygen species, and inhibiting the production of pro-inflammatory cytokines. Curcumin emerges as a promising therapeutic adjunct in Alzheimer's disease due to its multimodal neuroprotective benefits.

Application and Potential Value of Curcumin in Prostate Cancer: A Meta-Analysis Based on Animal Models
Frontiers in Pharmacology | April 2024
Curcumin is gaining recognition as an agent for cancer chemoprevention and is presently administered to humans. The findings of this meta-analysis demonstrated that curcumin exhibited a superior inhibitory effect on the volume of prostate cancer tumors in mice compared to the control group. Additionally, curcumin displayed a more effective inhibition of mice prostate cancer tumor weight. Furthermore, in terms of tumor inhibition rate, curcumin exhibited greater efficacy. Moreover, curcumin more effectively inhibited PCNA mRNA and MMP2 mRNA. Curcumin exhibited inhibitory properties towards prostate tumor growth and demonstrated a beneficial effect on prostate cancer treatment, thereby offering substantiation for further clinical investigations.

The mechanistic role of curcumin on matrix metalloproteinases in osteoarthritis
Fitoterapia | April 2024
Curcumin demonstrates significant improvements in inflammation, pain and function scores. Curcumin demonstrated significant inhibition of matrix metalloproteinases linked to cartilage degradation in Osteoarthritis through reduced activation of the nuclear factor kappa-B signaling pathway via suppressing phosphorylation of Iκβa and p65 nuclear translocation. Mechanistic evidence implicated matrix metalloproteinases in Osteoarthritis by decreasing Type II collagen, leading to cartilage damage. As a potential nutritional intervention for Osteoarthritis, curcumin could reduce inflammatory markers and improve pain and function scores. Curcumin, a bioactive compound from Curcuma longa, has been extensively studied for its anti-inflammatory properties [19]. Curcumin inhibits NFκB activation, reducing IL-1, IL-6, and TNF-α levels. In vitro studies have shown curcumin's ability to modulate MMPs by inhibiting NFκB activation in both animal and human chondrocytes [[13], [14], [15], [16], [17], [18]]. Human studies have reported significant improvements in inflammatory markers with curcumin treatment. This systematic literature review supports all three mechanistic hypotheses, demonstrating curcumin could inhibit MMPs and therefore osteoarthritis expression of cartilage damage. Curcumin was demonstrated to inhibit MMP-1, −3 and − 13 linked to cartilage degradation in osteoarthritis. Curcumin was also shown to inhibit MMPs by suppressing activation of the NFκB signaling pathway. This was observed by two means: curcumin's suppression of Iκβa phosphorylation and inhibition of p65 nuclear

Protective Effects of Curcumin and Resveratrol on Kidney Tissue on Cadmium- induced Oxidative Stress in Rats
Çanakkale Onsekiz Mart University | April 2024
Curcumin has a wide spectrum of effects, including anti- inflammatory, antioxidant, anticarcinogenic, antidiabetic, antiviral, and neuroprotective effects. It facilitates the removal of many reactive oxygen radicals, especially superoxide anions. In addition, it has been reported to scavenge ROS, inhibit lipid peroxidation, and protect cellular macromolecules from oxidative damage.In recent studies, curcumin has attracted attention for its potential antioxidant or anti-apoptotic properties. Curcumin has many beneficial properties, including antioxidant and anti-inflammatory actions (24-26). In this study, it was observed that the TAC level increased and the MDA level and OSI value decreased in the group administered curcumin with Cd. On the basis of our results, we can say that curcumin may benefit kidney tissue in cadmium-induced oxidative stress. As a result, both resveratrol and curcumin support the defense system of cells by scavenging free radicals that increase the oxidative damage caused by Cd in the kidneys.

Effect of curcumin on the expression of NOD2 receptor and pro-inflammatory cytokines in fibroblast-like synoviocytes of rheumatoid arthritis patients
Advances in Rheumatology | April 2024
Studies have shown that curcumin inhibits proliferation, migration, invasion, and Inflammation and on the other hand increases the apoptosis of rheumatoid arthritis FLSs. In this study, we aim to evaluate the effect of curcumin, a natural antiinflammatory micronutrient, on the expression of NOD2 and inflammatory cytokines. Administering curcumin alone or in combination whit MDP can significantly reduce mRNA expression levels of P65 and IL-6 in FLSs of both groups. Moreover, in FLSs of rheumatoid arthritis patients, a single curcumin treatment leads to a significant reduction in NOD2 gene expression. This study provides preliminary in vitro evidence of the potential benefits of curcumin as a nutritional supplement for rheumatoid arthritis patients. Despite the limitations of the study being an investigation of the FLSs of rheumatoid arthritis patients, the results demonstrate that curcumin has an anti-inflammatory effect on NOD2 and NF-κB genes. These findings suggest that curcumin could be a promising approach to relieve symptoms of rheumatoid arthritis.

Effects of curcumin supplementation on abdominal surgical wound healing
ACTA Cirúrgica Brasileira | April 2024
Numerous scientific studies have demonstrated the anti-inflammatory and antioxidant properties of curcumin, resulting in the reduction of free radicals and optimization of wound healing. In the present study, oral administration of curcumin via gavage demonstrated effectiveness in reducing blood vessels compared to the control group. Curcumin is a potential aid in wound contraction, as it accelerates the phases of the healing process. Its anti-inflammatory action is attributed to its ability to reduce inflammatory pathways, such as interleukin (IL)-1, IL-6, and transcription factors of protein I and nuclear factor kappa B (NfkB). During the proliferative phase, curcumin is capable of increasing reepithelialization speed, as well as granulation tissue and the amount of type III collagen. Oral curcumin supplementation was able to significantly reduce inflammatory parameters in both preoperative phase and postoperative phase (inflammatory infiltrate and blood vessel count) in abdominal surgical wounds of Wistar rats.

Curcumin intervention in hippocampal atrophy of diet-induced Alzheimer-like deficits in insulin-resistant rats
Rwanda Medical Journal | April 2024
Curcumin is a prime contender against pervasive diseases due to its efficacy, accessibility, affordability, and safety. The findings demonstrated that oral curcumin effectively corrected hyperglycemia and reduced insulin resistance. The study further revealed that insulin resistance was related to hippocampal atrophy and related deficits in the assessed rat model. Curcumin ameliorated these changes, reduced the aggregation of Aβ in the hippocampus, and reversed impaired signaling of proteins PI3K, AKT, and GSK-3β. The study's findings imply that oral curcumin has potential therapeutic advantages against prevalent neuronal death linked to abnormalities mimicking Alzheimer's disease and insulin resistance. Hence, curcumin may benefit dementia patients who also have insulin resistance.

Potential of Curcumin in the Management of Skin Diseases
Molecular Sciences | April 2024
Curcumin is a polyphenolic molecule derived from the rhizoma of Curcuma longa L. This compound has been used for centuries due to its anti-inflammatory, antioxidant, and antimicrobial properties. These make it ideal for preventing and treating skin inflammation, premature skin ageing, psoriasis, and acne. Additionally, it exhibits antiviral, antimutagenic, and antifungal effects. Curcumin provides protection against skin damage caused by prolonged exposure to UVB radiation. It reduces wound healing times and improves collagen deposition. Moreover, it increases fibroblast and vascular density in wounds. This review summarizes the available information on the therapeutic effect of curcumin in treating skin diseases. The results suggest that curcumin may be an inexpensive, well-tolerated, and effective agent for treating skin diseases. Curcumin has a broad spectrum of biological potentialities, of which anti-inflammatory and cardioprotective effects are most often investigated. Turmeric, which is the main source of curcumin, is known for its health-promoting properties since the ancient times. There is an increasing number of studies that state that curcumin can modulate phenomena associated with inflammatory, infectious, and proliferative skin diseases.  It is applied for health-promoting purposes due to its multidirectional action, of which its antioxidant activity is a very important issue.

Curcumin inhibits the growth and invasion of gastric cancer by regulating long noncoding RNA
World Journal of Gastrointestinal Oncology | April 2024
Curcumin, a natural anticancer agent, exhibits therapeutic promise in gastric cancer. Its effects include promoting cell apoptosis, curtailing tumor angiogenesis, and enhancing sensitivity to radiation and chemotherapy. Curcumin exerts anticancer effects by inhibiting cell cycle progression and promoting apoptosis. Numerous studies have substantiated the antitumor properties of curcumin, whether used in isolation or in conjunction with other pharmaceutical agents. Research has shown that curcumin can diminish H19 expression while augmenting P53 in GC cells, thereby manifesting antiproliferative effects. Our experimental findings corroborate that curcumin markedly curtails the proliferation of GC cells, including AGS, MGC-803, and BGC-823 cells. Curcumin has potential anticancer effects on gastric cancer cells by regulating RNA.

Role of Curcumin in the Management of Rheumatoid Arthritis and Psoriatic Arthritis
Psoriasis - Recent Advances in Diagnosis and Treatment | April 2024
Curcumin, the primary active component within Curcuma longa (turmeric), has been demonstrated to be helpful in treating rheumatoid arthritis and psoriatic arthritis, with effectiveness attributed to its mode of activity. The antiarthritic effect of curcumin has been investigated in patients with rheumatoid arthritis. In one study, 45 participants was randomly allocated to one of three groups: treatment with 500 mg of curcumin, treatment with 50 mg of diclofenac sodium, or a combination of the two. The Disease Activity Scores of patients across all three groups showed significant statistical improvement. However, the curcumin group showed superior results and had the highest percentage of recovery. According to the American College of Rheumatology score, the curcumin group also exhibited the greatest reduction in pain and joint edema. According to various literature surveys and evidence, it can be concluded that curcumin is a safe and effective therapeutic option for managing rheumatoid arthritis and psoriatic arthritis compared to synthetic medications.  Turmeric regulates inflammation, cell development, and apoptosis, making it suitable for both prevention and treatment of various ailments due to its antioxidant and anti-inflam- matory applications, along with its high safety profile, the bulk of which is attributed to curcumin. Curcumin interacts with a wide variety of molecular domains, making it a pleiotropic chemical. According to in vitro and in vivo research, curcumin is a promising curative drug for various chronic illnesses, including pancreatitis, inflammatory bowel disease, chronic anterior uveitis, and certain malignancies. Curcumin’s physiological actions or molecular processes have been explored in numerous cell and animal investigations, and research is ongoing. Curcumin has attracted attention as a possible rheumatoid arthritis treatment due to its antioxidant properties and regulatory role of associated inflammatory agents. Curcumin, an antioxidant, anti-inflammatory, and immune-modulatory agent, is found in turmeric. It has been found to assist with arthritis and joint pain. Given that persistent inflammation is a key feature of arthritis, it is important to note that curcumin has been reported to be beneficial for both inflammatory bowel disease and irritable bowel syndrome. Additionally, curcumin may potentially help reduce neuroinflammation associated with Alzheimer’s disease. Recent studies suggest that curcuminoids, when combined with black pepper, may help alleviate the painful joint symptoms associated with RA, PsA, or OA. Curcumin can help the immune response by reducing inflammation, which can help to alleviate joint discomfort, increase mobility, and restore functioning in troublesome regions. Curcumin’s anti-inflammatory properties have been proven in several trials, including investigations of back pain, muscular discomfort, and inflammation associated with asthma and allergies. Curcumin has been demonstrated to be safe and effective in treating rheumatoid arthritis and psoriatic arthritis. Curcumin has proven beneficial in effectively treating both diseases without adverse side effects, potentially leading to symptom improvement in both conditions.

Curcumin is comparable to metformin for the treatment of PCOS in rats: a preclinical study
Pharmacia | April 2024
Curcumin, the active ingredient in turmeric (Curcuma longa Zingiberaceae) is a yellow polyphenol with a wide range of pharmacological activities such as antioxidant, anti-inflammatory, anti-tumor, neuroprotective and cardioprotective properties. Weight was significantly reduced in the curcumin, metformin and curcumin and metformin combination groups. Curcumin is therapeutically effective for PCOS and is comparable to metformin. Curcumin is a major herbal constituent of turmeric (Nelson et al. 2017), it had been used in herbal medicine for ages, partially for its anti-inflammatory effects (Mahdizadeh et al. 2015). Curcumin, that golden concoction, is used for almost every ailment, acute and chronic (Amalraj et al. 2017; Kunnumakkara et al. 2017). From cancer to obesity, no health problem has not been presumed to profit from curcumin, mainly due to curcumin’s antineoplastic, antioxidant, antimicrobial, and anti-inflammatory qualities (Kocaadam and Şanlier 2017; Li et al. 2018). Increasingly available evidence is accumulating regarding curcumin potential efficacy for pulmonary diseases (Lelli et al. 2017). Curcumin has also shown the potential to be effective for skin diseases such as psoriasis, atopic dermatitis, and wound care (Vollono et al. 2019). Additionally, curcumin is non-toxic and safe for humans’ consumption (Soleimani et al. 2018). Curcumin anti-inflammatory properties make it potentially useful for many disorders and ailments whose pathophysiological basis implicates inflammation. Type II diabetes (T2D) a prevalent modern world disorder, is also potentially responsive to curcumin in pre- and clinical studies (Pivari et al. 2019). Endometriosis, a gynecological disorder marked by inflammation, appears to benefit from the anti-inflammatory effects of curcumin (Arablou and Kolahdouz-Mohammadi 2018). Curcumin effects were expected as it had been shown to be effective for many disorders including gynecological disorders (Arablou and Kolahdouz-Mohammadi 2018). One possible mechanism for curcumin effects on PCOS signs might be its antioxidant powers as oxidative stress has a role in pathogenesis of PCOS (Ryu et al. 2019). Curcumin anti-inflammatory properties also most probably contribute to its effectiveness in disorders such as PCOS (Salehi et al. 2019). Also, the effect of curcumin could be through its beneficial effects on glucose tolerance and lipid profile which when improved can also improve symptoms of PCOS. Curcumin improved insulin sensitivity and lipid profiles in rats’ models of type 2 diabetes (Francesca Pivari, Alessandra Mingione 2019). This study did not attempt to examine the exact mechanism of curcumin effects in this model of PCOS. Thus, we cannot be certain about the mechanism(s) of curcumin in improving symptoms of PCOS in this study.

Network pharmacology and molecular docking reveal the mechanisms of curcumin activity against esophageal squamous cell carcinoma
Frontiers in Pharmacology | April 2024
Curcumin displays anti-cancer activity against various cancers. Numerous lines of evidence indicate that curcumin has a potential in the management of various forms of cancer, including prostate cancer (Termini et al., 2020), colorectal cancer (Pricci et al., 2020), breast cancer (Deng et al., 2022), endometrial carcinoma (Zhang et al., 2019) and non-small cell lung cancer (Xie et al., 2022). Curcumin has potential anti-ESCC activity. For instance, curcumin can induce apoptosis and enhance the sensitivity of fluorouracil ESCC cell death by suppressing the NF-κB signaling pathway (Tian et al., 2012). According to Deng and his colleagues, the combination of curcumin and docetaxel triggers cell death and self-degradation in ESCC cells through the PI3K/AKT/mTOR signaling pathway (Deng et al., 2021). In ESCC cells, curcumin inhibits STAT3-mediated signaling and induces apoptosis and growth arrest (Liu et al., 2018). Curcumin has been widely used in cancer treatment (Bar-Sela et al., 2010; Zoi et al., 2021). A recent study found that curcumin has the ability to regulate the circNRIP1/miR-532-3p/AKT pathway, resulting in the suppression of ESCC (Luo et al., 2023). Furthermore, curcumin induces apoptosis (Liu et al., 2018; Deng et al., 2021) and suppresses esophageal squamous cell carcinoma cell proliferation (Hosseini et al., 2018), and blocks the growth of primary esophageal squamous cell carcinoma-derived xenografts in vitro (Liu et al., 2018). Based on the findings from the GO and KEGG analyses, curcumin has the potential to address esophageal squamous cell carcinoma by modulating pathways related to cell cycle, programmed cell death, and cellular aging. Our experiments showed that curcumin induced a pause in the cell cycle at the G2/M and S stages. CCK8 experiments and clone formation assays indicated that curcumin significantly inhibited esophageal squamous cell carcinoma cell proliferation. Furthermore, Transwell invasion assays demonstrated that curcumin inhibited esophageal squamous cell carcinoma cell invasion and SA-β-gal measurement indicated that curcumin can induce esophageal squamous cell carcinoma cell senescence. Western blot results showed that curcumin may treat esophageal squamous cell carcinoma by inhibiting CDK2/RB pathway. 5 Conclusion In summary, our findings from network pharmacology, molecular docking, and in vitro experimental confirm that curcumin possesses the capacity to inhibit the proliferation and invasion of esophageal squamous cell carcinoma cells. This is achieved through the induction of cell cycle arrest, regulation of FoxO, cell senescence, IL-17, and many cancer-related signaling pathways. Curcumin may exert anti-ESCC effects by interacting with CHEK1, TOP2A, CDK2, AURKA, CDK6, DHFR, EGFR, STAT3, PPARG, and SERPINE1CUR arrested ESCC cells at the G2/M and S phases, as shown by flow cytometry. Colony formation and CCK8 assays showed that curcumin can inhibit the proliferative ability of esophageal squamous cell carcinoma cells. The Transwell invasion results validated that curcumin can significantly inhibit the invasion rates of esophageal squamous cell carcinoma cells. Collectively, these findings indicate that curcumin exhibits pharmacological effects on multiple targets and pathways in esophageal squamous cell carcinoma.

The Effects of Curcumin Plus Piperine Co-administration on Inflammation and Oxidative Stress: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Current Medicinal Chemistry | April 2024
Results indicated that curcumin plus piperine administration could effectively reduce oxidative stress and inflammation. The beneficial effects of curcumin against various chronic disorders have been shown in the last few decades. Piperine has been used in scientific evaluations as an effective compound to increase the bioavailability of curcumin. According to the current meta-analysis, curcumin plus piperine administration showed a significantly increased SOD activity and GSH levels while significantly decreased MDA concentrations. In addition, our study revealed that curcumin plus piperine significantly decreased TNF-α and IL-6 concentrations.

NF-κB pathway as a molecular target for curcumin in diabetes mellitus treatment: Focusing on oxidative stress and inflammation
Authorea | April 2024
This study extensively explores the prospective therapeutic benefits of curcumin, a bioactive compound known for its antioxidant, anti-inflammatory, and hypoglycemic properties, in addressing diabetic complications, predominantly via the modulation of the NF-κB pathway. The findings reveal that curcumin administration effectively lowered blood glucose elevation, reinstated diminished serum insulin levels, and enhanced body weight in Streptozotocin -induced diabetic rats. Curcumin exerts its beneficial effects in management of diabetic complications through regulation of signaling pathways, such as CaMKII, PPAR-γ, NF-κB, and TGF-β1. Moreover, curcumin reversed the heightened expression of inflammatory cytokines (TNF-α, IL-1β, IL-6) and chemokines like MCP-1 in diabetic specimens, vindicating its anti-inflammatory potency in counteracting hyperglycemia-induced alterations. Curcumin diminishes oxidative stress, avert structural kidney damage linked to diabetic nephropathy, and suppress NF-κB activity. Furthermore, curcumin exhibited a protective effect against diabetic cardiomyopathy, lung injury, and diabetic gastroparesis. Conclusively, the study posits that curcumin could potentially offer therapeutic benefits in relieving diabetic complications through its influence on the NF-κB pathway. Curcumin has shown potency against numerous chronic conditions like Alzheimer’s disease, T2DM, rheumatoid arthritis, and metabolic syndrome. It possesses a broad spectrum of therapeutic properties, including antineoplastic, antimicrobial, anti-carcinogenic, anti-mutagenic, anti-aging, anti-inflammatory, anti-proliferative, anti-amyloid, and anti-hypercholesterolemic effects. Mechanistically, curcumin inhibits the initiation of the radical-sensitive transcription factor NF-κB, reduces cytokine production, and impedes vital cellular survival processes. It also inhibits STAT proteins and NF-κB-DNA binding, diminishing the expression of pro-inflammatory molecules MMP-9, MMP-3, and cytokines like TNF-α, IL-1, and IL-8. Furthermore, curcumin attaches to the COX-2 protein, curtailing COX-2 expression and the synthesis of prostaglandins and thromboxanes [61]. Clinical trials have consistently affirmed curcumin’s assurance, acceptability, and effectiveness in addressing diverse chronic disorders in humans. These trials reported no toxicity when curcumin was given by mouth at a daily dose of 6 g for a duration of 4 to 7 weeks. The study underscores curcumin’s potential as a therapeutic agent in mitigating diabetes mellitus complications, primarily through modulating the NF-κB pathway. By demonstrating anti-inflammatory, antioxidative, and anti-fibrotic properties, curcumin has been effective in managing multiple diabetic conditions, including nephropathy, cardiomyopathy, and gastroparesis. The alteration of critical signaling pathways such as CaMKII, PPAR-γ, NF-κB, and TGF-β1 is pivotal in curcumin’s beneficial effects. Additionally, its capacity to diminish OS, curb inflammation, and enhance vascular functionality vindicate curcumin as a promising candidate molecule for management of diabetes mellitus complication. These findings highlight the necessity to further explore the potential of curcumin as a supplementary treatment option in management of diabetes mellitus complications.

Regulatory effects of curcumin on nitric oxide signaling in the cardiovascular system
Nitric Oxide | April 2024
Curcumin improves cardiovascular function, acting as an anti-inflammatory, antioxidant, and increasing bioavailability of nitric oxide. The major component of Curcuma longa, curcumin, has long been utilized in traditional medicine to treat various illnesses, especially cardiovascular diseases. Curcumin's pharmacological effects have been well studied. It works by lowering the generation of ROS, restricting the entrance of potassium, suppressing NF-κB, extracellularly regulated protein kinases (ERK) 1/2 and c-Jun N-terminal kinase (JNK), and preventing the activity of apoptosis-associated speck-like protein (ASC). Furthermore, curcumin stimulates the sirtuin1 (SIRT1)-forkhead box transcription factor O1 (FOXO1) axis, which decreases cardiac oxidative stress levels and debilitates myocardial apoptosis. By the SIRT1/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3)/B-cell lymphoma-2 (Bcl-2)/Beclin-1 autophagy axis, curcumin may also preserve cardiomyocytes. Curcumin enhances left ventricular function in pressure-overloaded rabbits by inhibiting collagen remodeling and reducing the expression of TNF-a and MMPs in the myocardium. Tharaux et al. demonstrated that curcumin inhibits fibrosis in the aorta and renal arteries, preserving vessel wall elasticity. Curcumin was found to exert these effects by inhibiting the renin-angiotensin system-transforming growth factor β1 (TGF-β1) collagen axis. Curcumin improves cardiovascular function as well as having important pleiotropic effects, such as anti-inflammatory and antioxidant, through its ability to increase the bioavailability of nitric-oxide and to positively impact nitric-oxide related signaling pathways. 

Protective Effect of Curcumin on D-Galactose-Induced Senescence and Oxidative Stress in LLC-PK1 and HK-2 Cells
Antioxidants | April 2024
Curcumin has been reported to exert antioxidant, anti-inflammatory, antimutagenic, antimicrobial, hypoglycemic, and anticancer effects. Moreover, its safety, tolerability, and non-toxicity have been reported in clinical trials. Regarding its antioxidant effects, curcumin is a bifunctional antioxidant. It has two phenol groups which confer a high hydrogen-donating activity and directly scavenges ROS. Furthermore, this curcumin polyphenol increases the activity of antioxidant enzymes such as CAT, SOD, glutathione peroxidase, and heme oxygenase-1 through the activation of nuclear factor erythroid 2-related factor (Nrf2) that induces the expression of genes coding for elements of the antioxidant system. Furthermore, curcumin has also been considered an anti-aging and senolytic agent in different in vitro and in vivo models. Curcumin, through its antioxidant properties, decreased DNA damage and reduced the number of senescent cells, preventing the decrease in lamin B1 in LLC-PK1 cells. It has been observed that the expression of lamin B1 is decreased by oxidative stress and is related to the senescent phenotype. Our results show that curcumin prevents changes induced by D-galactose in different senescence markers, notably β-galactosidase activity (decrease of 20% in LLC-PK1 cells) and PCNA (decrease of 60% in HK-2 cells). Moreover, it decreases oxidative stress (ROS reduction of 20% in both cell lines) and oxidative damage (8-OHdG reduction of 25% in LLC-PK1 cells) caused by D-galactose treatment. Therefore, curcumin has a moderate protective effect on D-galactose-induced senescence and oxidative stress in LLC-PK1 and HK-2 cells and could be further considered as a possible therapeutic agent. Curcumin treatment decreased by 20% the number of cells positive for senescence-associated (SA)-β-D-galactosidase staining and by 25% the expression of 8-hydroxy-2′-deoxyguanosine (8-OHdG) and increased by 40% lamin B1 expression. In HK-2 cells, curcumin treatment increased by 60% the expression of proliferating cell nuclear antigen (PCNA, 50% Klotho levels, and 175% catalase activity. In both cell lines, this curcumin antioxidant decreased the production of ROS (20% decrease for LLC-PK1 and 10 to 20% for HK-2). These data suggest that curcumin treatment has a moderate protective effect on D-galactose-induced senescence in LLC-PK1 and HK-2 cells.

The Modulatory Effects of Curcumin on the Gut Microbiota: A Potential Strategy for Disease Treatment and Health Promotion
Microorganisms | March 2024
In addition to its antioxidant properties, curcumin exhibits various other biological activities, such as anti-inflammatory effects, the modulation of lipid metabolism, and the modulation of the immune system. These activities contribute to its potential as an anticancer, antitumor, and antithrombotic agent. Furthermore, curcumin is known to interact with various cellular and molecular targets, including growth factors, chemokines, transcription factors, and cell adhesion molecules, further enhancing its therapeutic potential. The contradiction with the low bioavailability of curcumin and its diverse pharmacological activities could be resolved by considering the interactions of curcumin with the gut microbiota. Since this discovery, a large number of clinical trials started to explore the therapeutic potential of curcumin for a variety of human diseases, namely cancer, cardiovascular diseases, neurodegenerative diseases, and inflammation. The latest research indicates elevated levels of curcumin in the gastrointestinal system after the oral intake of curcumin. It has been proposed that curcumin interacts dynamically with the intestinal microbiota, modulating the composition and activity and exerting a potential therapeutic effect on diseases caused by the dysbiosis of the intestinal flora. It has been found that oral curcumin supplementation is able to target improvements in gut barrier function and that higher levels of curcumin residues have been found in the gut after oral curcumin administration, emphasizing the possible positive effects of curcumin on the gut microbiota. The important biological activities of curcumin, such as anti-inflammatory, antioxidant, anti-obesity, and anticancer, have long been demonstrated, and it is able to fully utilize its pharmacological effects through various molecular targets. The anti-inflammatory effect of curcumin is mainly achieved by inhibiting the NF-κB, reducing the release of a variety of pro-inflammatory factors, accompanied by the scavenging of free radicals and the downregulation of ROS generation, thereby reducing oxidative stress and exerting its antioxidant effects. Therefore, curcumin can improve the occurrence and development of atherosclerosis and inflammatory bowel disease. In addition, curcumin maintains intestinal barrier function by regulating multiple signaling pathways to prevent damage from dietary factors or endogenous injury. Secondly, curcumin can regulate lipid metabolism and production through MPAK signaling, thus achieving the goals of treatments for obesity.

Curcumin as a regulator of Th17 cells: Unveiling the mechanisms
Food Chemistry Oxford | March 2024
Curcumin exhibits anticancer, anti-inflammatory, and antioxidant characteristics (Chatterjee and Pandey, 2011, Marjaneh et al., 2018, Zahedi et al., 2023, Mohajeri and Sahebkar, 2018). In the past two decades, studies have found that curcumin has immunomodulatory effects, regulating the activity of immune cells. Recent reports have shown that curcumin can reduce the proliferation of alloreactive T cells and significantly suppress the differentiation of Th17 cells (Park et al., 2013). Curcumin also suppresses the production of pro-inflammatory cytokines, including IL-17 and TNF-α, in Th17 cells, thereby reducing the expression of inflammatory cells, particularly neutrophils, and resulting in decreased inflammation and infiltration (Mohammadian Haftcheshmeh et al., 2021). Curcumin demonstrates promise in regulating T cell subsets associated with inflammatory diseases. Xiao et al. (Xiao et al., 2022) reported that curcumin downregulated pro-inflammatory Th17 cells (CD4 + CCR6 + Th17, CD4 + IL-17A + Th17, IL-17A, BATF, C-Maf, RORγt) and upregulated anti-inflammatory Treg cells (CD4 + Foxp3 + Treg, CD4 + IL-10 + Treg, IL-10, Foxp3, Eomes) in mice with diabetic colitis, suggesting its ability to restore Th17/Treg balance. Human studies on curcumin's systemic bioavailability, metabolites, and pharmacokinetics have primarily focused on patients with cancer. Garcea et al. (Garcea et al., 2005) found that patients with different stages of colorectal cancer who took 3.6 g of curcumin for 7 days had pharmacologically effective concentrations of curcumin in both normal and colorectal tissue (Menozzi et al., 2009). Curcumin has several roles in the regulation of enzymes involved in inflammation, adhesion molecules, transcription factors, protein kinases, cytokines, and redox balance. It possesses various pharmacological functions, including antimicrobial, antitumor, anti-inflammatory, antiviral, antioxidant, and antifungal properties (Howells et al., 2021, Heidari et al., 2023, Bagheri et al., 2020, Cicero et al., 2020, Keihanian et al., 2018, Khayatan et al., 2022, Mokhtari-Zaer et al., 2018, Panahi et al., 2019, Sahebkar, 2010, Sahebkar, 2014, Iranshahi et al., 2010, Mohammadi et al., 2019, Panahi et al., 2012). It also plays a protective role against autoimmune diseases. Several studies have demonstrated that curcumin can enhance the antitumor effects of chemotherapeutics, including paclitaxel, against various cancers while also reducing the side effects of conventional chemotherapies (Ashrafizadeh et al., 2020). Curcumin acts as an active scavenger of reactive oxygen species (ROS) and reactive nitrogen species. Moreover, it increases the synthesis of glutathione (GSH), a crucial intracellular antioxidant (Menon and Sudheer, 2007, Zheng et al., 2017). Curcumin also plays a role in protecting against catalase activities and reducing the levels of glutathione S-transferases (GST), superoxide dismutase (SOD), and glutathione peroxidase (GPx) (Arshad et al., 2017). Because oxidative stress is closely related to inflammation, curcumin indirectly inhibits pro-inflammatory reactions in the immune system (He et al., 2015). Notably, curcumin is a potent immunomodulator, with strong interactions with different types of immune cells, including neutrophils, T cells, mast cells, epithelial cells, eosinophils, and basophils, resulting in the regulation of pathological immune system reactions (Panahi et al., 2015, Mohammadi et al., 2022, Rahimi et al., 2019). The immunomodulatory effects of curcumin, which confer protection against immune-mediated diseases, are attributed to its ability to interact with cells of the immune system (Gao et al., 2004, Gautam et al., 2007, Momtazi-Borojeni et al., 2018). Curcumin can influence both the innate and adaptive immune reactions (Haftcheshmeh et al., 2022, Gao et al., 2004). Curcumin's immunomodulatory properties arise from its ability to modulate the expression of numerous pro-inflammatory chemokines and cytokines, including interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, and monocyte chemoattractant protein-1 (MCP-1) (Haftcheshmeh et al., 2022, Gao et al., 2004, Momtazi-Borojeni et al., 2018, Panahi et al., 2016). Curcumin, an active compound found in turmeric, exhibits potent immunomodulatory effects, making it a promising therapeutic agent for various inflammatory and autoimmune disorders. Recent studies have focused on the ability of curcumin to modulate Th17-mediated immune responses, which play a critical role in the development of several autoimmune diseases. Curcumin has been shown to inhibit the proliferation and differentiation of Th17 cells and reduce the production of specific pro-inflammatory cytokines such as IL-17, IL-6, and TNF-α. Additionally, curcumin has been found to increase the production of Treg cells, which suppress excessive immune responses and maintain immune homeostasis. Overall, curcumin's ability to target the Th17 axis opens exciting avenues for developing novel therapeutic strategies for autoimmune and inflammatory diseases.

Phytocompounds-based therapeutic approach: Investigating curcumin and green tea extracts on MCF-7 breast cancer cell line
Journal of Genetic Engineering and Biotechnology | March 2024
Results showed the anticancer and cytotoxic properties of curcumin against MCF-7 cells, with a relatively higher level of released LDH. The curcumin extract downregulated the oncogenic Raf-1, suppressed the Telomerase and upregulated the TNF-α and IL-8 genes. Results from the ELISA showed a notable increase in IL-8 and TNF-α cytokines levels after curcumin treatment, which culminated after 72 h. Among both extracts, only curcumin effectively modulated the understudy molecular targets, achieving multi-targeting anticancer activity against MCF-7 cells. Moreover, the applied dosage significantly increased levels of the proinflammatory cytokines, which represent a component of the cytokines-targeting-based therapeutic strategy.

Cytotoxic evaluation of curcumin and quercetin in MCF-7 cell lines
World Journal of Biology Pharmacy and Health Sciences | March 2024
Curcumin, a naturally occurring compound found in turmeric, has been extensively studied for its potential anticancer properties, including its effects on MCF-7 cell lines. MCF-7 cells are commonly used as a model for studying breast Anti-Inflammatory Effects: Both curcumin and quercetin possesses anti-inflammatory properties, and chronic inflammation is often associated with cancer development. By reducing inflammation, curcumin may indirectly contribute to the cytotoxic effect on cancer cells. In this study, the cytotoxic potential of a curcumin was found to be greater than the cytotoxic potential of quercetin in the individual testing, however the phyto nutrient combination & natural extracts of both curcumin and quercetin shows the better cytotoxic potential in the MCF7 Breast cancer cell line. The combination of both the phytoconstituents shows an effective synergistic effect that can elicit a powerful cytotoxic response on the breast cancer cells. The synergistic effects observed in the combination of curcumin and quercetin on MCF-7 cells suggest that the compounds may act through complementary mechanisms, enhancing their individual anticancer activities.

Impact of Curcumin on Aging: Manifestations and Limitations
Curcumin and Neurodegenerative Diseases | March 2024
Due to its potential for treating cancer and Alzheimer’s disease, turmeric, which contains curcumin, has gained considerable attention in recent years. The primary reason why curcumin is effective is its anti-inflammatory properties. Age-related redox imbalance results in overexpression of reactive oxygen species levels. Curcumin reduces oxidative stress associated with cellular senescence and can benefit aging individuals.

Exploring the molecular mechanism of action of curcumin for the treatment of diabetic retinopathy, using network pharmacology, molecular docking, and molecular dynamics simulation
Integrative Medicine Discovery | March 2024
A wide range of pharmacological properties have been attributed to curcumin, including antioxidant, anti-inflammatory, antimutagenic, etc. Researchers found that curcumin had a beneficial effect on the expression of vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α), and pro-inflammatory cytokines in the retina of diabetic rats. In addition, curcumin has also been demonstrated to have the capability of slowing down or even reversing the progression of certain fundus diseases, making it a new option for the treatment of retinal diseases. As a result of this study, curcumin may exert a role in the treatment of diabetic retinopathy through multi-target and multi-pathway regulation, which indicates a possible direction of future research. In summary, through network pharmacology, molecular docking, and MD simulations, the present study investigated the potential mechanisms of curcumin in the treatment of diabetic retinopathy. Following its introduction into the body, curcumin has multiple targets and pathways for treating diabetic retinopathy. Several targets were shown to be used by curcumin to exert anti-diabetic retinopathy effects, including AKT1, IL-1B, IL-6, ALB, and TNF-α, and regulating several signaling pathways such as PI3K-Akt signaling pathway, lipid and atherosclerosis signaling pathway, and AGE-RAGE signaling pathway in diabetic complications.

Curcuma longa: A Natural Ally in Alzheimer’s Disease Management
Curcumin and Neurodegenerative Diseases | March 2024
Curcuma longa, commonly known as turmeric or saffron, contains a compound called curcumin that possesses potential biopharmacological activity. Curcumin is considered safe by the American Food and Drug Administration (FDA) and does not exhibit any side effects when consumed in moderate amounts. Numerous studies have been conducted on curcumin due to its therapeutic potential in various diseases, particularly in neurodegenerative disorders such as Alzheimer’s disease. Research indicates that this substance holds remarkable potential as an effective and safe treatment.

Curcumin activates the JNK signaling pathway to promote ferroptosis in colon cancer cells
Chemical Biology & Drug Design | March 2024
Recent evidence has proved that curcumin as a natural polyphenol has anticancer and anti-proliferative effects in cancer cells. Curcumin suppressed SW-480 cancer cells viability in dose-dependent manner. Cell treatment with curcumin led to accumulation of ROS and iron within cells and increase in the intracellular levels of lipid peroxidation. In addition, curcumin modulated the mRNA and protein expression levels of ferroptosis-related proteins including ACSL4, GPx4 and FTH1 and suppression of JNK signaling. Curcumin may exhibit its anticancer effect on colorectal cancer by downregulating JNK signaling to induce ferroptosis in SW-480 cells.

Longevity and anti-aging effects of curcumin supplementation
GeroScience | March 2024
Curcumin demonstrated a positive impact on slowing down the aging process by postponing age-related changes. Curcumin may have anti-aging properties by changing levels of proteins involved in the aging process, such as sirtuins and AMPK, and inhibiting pro-aging proteins, such as NF-κB and mTOR. In clinical research, this herbal compound has been extensively examined in terms of safety, efficacy, and pharmacokinetics. There are numerous effects of curcumin on mechanisms related to aging and human diseases.

Curcuminoids with Antineurodegenerative Properties: Current Trends and Future Perspectives
Curcumin and Neurodegenerative Diseases | March 2024
Curcuminoids are bioactive compounds found in Curcuma longa Linn. (Zingiberaceae), a species commonly known as turmeric or turmeric root, widely used in traditional medicine for centuries. Recent research has demonstrated the potential of these metabolites as antineurodegenerative agents, substances that can help prevent or treat neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. Studies have focused on understanding the molecular mechanisms by which curcuminoids exert their antineurodegenerative properties, as well as developing more effective and bioaccessible formulations of these compounds to improve their bioavailability and ability to cross the blood–brain barrier. Additionally, research has explored the combination of curcumin with other substances or therapies, such as combining them with other natural compounds, conventional drugs, or non-pharmacological therapies like deep brain stimulation.

Curcumin protects mice with myasthenia gravis by regulating the gut microbiota, short-chain fatty acids, and the Th17/Treg balance
Heliyon | March 2024
Curcumin modified the gut microbiota composition, increased microbial diversity, and, in particular, reduced endotoxin-producing Proteobacteria and Desulfovibrio levels in T-AChR-induced gut dysbiosis. Moreover, we found that curcumin significantly increased fecal butyrate levels in mice with T-AChR-induced gut dysbiosis. In addition, curcumin repressed the increased levels of lipopolysaccharide (LPS), zonulin, and FD4 in plasma. Curcumin enhanced Occludin expression in the colons of MG mice induced with T-AChR, indicating dramatically alleviated gut permeability. Furthermore, curcumin treatment corrected T-AChR-induced imbalances in Th17/Treg cells. Curcumin modifies gut microbiota composition and increases the abundance of SCFA-producing bacteria. Curcumin reduced FD4 concentrations as well as LPS and zonulin levels in serum.  Curcumin supplementation increased the level of butyrate and regulated the TH17/Treg balance.  Curcumin is an effective constituent of the traditional Asian medicine turmeric with antioxidant, anti-inflammatory and neuroprotective properties. Of note, curcumin has been recently proposed for the management of neurological diseases by regulating the gut microbiota and improving gut barrier function. It was reported that curcumin could considerably alter the ratio of pathogenic and beneficial bacteria by reducing the relative abundance of genera including Prevotellaceae, Coriobacterales, Enterobacteria, and Enterococci while increasing the relative abundance of favorable genera including Bifidobacteria and Lactobacilli. Hence, curcumin seems to have promising clinical applications. We found that curcumin alleviated the clinical symptoms, corrected the microbiota imbalance, increased SCFA-producing bacteria, reduced intestinal permeability, and regulated the Th17/Treg balance in T-AChR-induced MG mice. Considering the protective effect of curcumin on the gut microbiota and the regulation of immune responses by SCFAs, we evaluated the concentrations of SCFAs in the feces by using GC‒MS. In the T-AChR-induced EAMG group, fecal acetic acid and butyric acid concentrations were decreased, whereas curcumin administration reversed this reduction. These changes may be directly correlated to the abundance of the genera Oscillospira, Akkermansia, and Allobaculum. Curcumin has been proven to be neuroprotective and anti-inflammatory in both humans and animals; furthermore, curcumin is used to treat Huntington's disease, Alzheimer's disease, and cerebral ischemia.According to our study, curcumin alleviated the clinical symptoms of MG mice, which was consistent with previous reports. In addition, curcumin altered the gut microbiota composition, increased SCFA-producing bacteria, reduced intestinal permeability, and regulated the Th17/Treg balance of T-AChR-induced MG mice.  Curcumin and its metabolites have been demonstrated to affect the gut microbiota. Our findings have revealed that curcumin could restore the original gut microbial composition in T-AChR-induced MG mice and increase the abundance of a few important bacterial species. However, the disorders of the gut microbiota during EAMG were restored after treatment with curcumin, which mainly manifested as an increase in gut microbial diversity and richness. Consistently, curcumin increased the frequency of CD4+ CD25+ Foxp3+ Tregs and decreased the frequency of CD4+ IL-17A+ Th17 cells in spleens and inguinal lymph nodes. This shows that curcumin has the ability to restore the imbalance of Th17/Treg cells in T-AChR-induced MG mice. As a result, the host's immune system contributes to the beneficial effects.

Curcumin Promotes Diabetic Foot Ulcer Wound Healing by Inhibiting miR-152-3p and Activating the FBN1/TGF-β Pathway
Molecular Biotechnology | March 2024
Curcumin has been used as a traditional remedy for inflammation and wound healing, and it works at diverse stages, such as inflammation, maturation, and proliferation, thereby accelerating the entire process of wound healing. Studies have shown that curcumin treatment can cause fibroblasts to infiltrate into the wound site and accelerate wound healing. In addition, curcumin has been found to be beneficial for  diabetic foot ulcer and may be a potential candidate for treatment. Curcumin inhibited the apoptosis of fibroblasts, promoted their migration ability, and alleviated the damage of fibroblasts stimulated by HG. Furthermore, curcumin treatment promoted angiogenesis and accelerated wound healing in  diabetic foot ulcer rats. This suggests that curcumin plays an important role in the process of alleviating  diabetic foot ulcer. According to previous studies, there are many miRNAs involved in the treatment of different diseases by curcumin. Studies have shown that curcumin can attenuate vascular calcification through the exosomal miR-4b-92p/KLF3 axis, and curcumin therapy protects PC12 cells from high glucose-induced inflammatory responses. Curcumin alleviates the progression of  diabetic foot ulcer by inhibiting miR-152-3p.  In summary, curcumin activates the FBN1/TGF-β pathway by inhibiting miR-152-3p, thereby inhibiting HG-induced fibroblast apoptosis, promoting fibroblast proliferation and migration, alleviating HG-induced fibroblast damage, and promoting angiogenesis in  diabetic foot ulcer rats, thereby accelerating wound healing in  diabetic foot ulcer rats. This provides a new theoretical basis for curcumin treatment of DFU and may become a potential therapeutic target for diabetic foot ulcer.

Effects of Turmeric (Curcuma longa) on the Gut-Brain Axis
Curcumin and Neurodegenerative Diseases | March 2024
Turmeric is a spice widely known for its medicinal properties, including its effects on gut and neurobehavioral health. The results showed that curcumin is the most studied bioactive compound in turmeric. In vitro and in vivo studies with animal models have demonstrated antioxidant, anti-inflammatory, antiviral, and anticancer properties of turmeric and its isolated compounds. Some studies have shown the effects of this spice against gastrointestinal diseases, on the balance of the intestinal microbiota, and neurobehavioral parameters.

Preservative Effects of Curcumin on Semen of Hu Sheep
Animals | March 2024
Curcumin is a diketone compound found in the rhizomes of ginger plants that can neutralize ROS and improve the activity of endogenous antioxidant enzymes in the body. Curcumin can also promote Nrf2 nuclear transport by inhibiting the binding of Keap1 to Nrf2, thereby upregulating the Nrf2/ARE pathway, which increases the levels of HO-1 and NQO1 and improves antioxidant activity in the body. Curcumin has been widely used in feed additives, which can enhance the antioxidant capacity of animals and promote the nutrient absorption rate in the gut. These results show that adding an appropriate concentration (20 µmol/L) of curcumin to sheep semen can affect sphingosine-1-phosphate, dehydroepiandrosterone sulfate, phytosphingosine, and other metabolites of semen, inhibit ROS production, and prolong the time of cryopreservation.

Cardioprotective Effects of Curcumin Against Diabetic Cardiomyopathies: A Systematic Review and Meta-Analysis of Preclinical Studies
Traditional and Western Medicine Center for Cardiovascular | March 2024
Meta-analysis showed that curcumin significantly improved cardiac function indices, decreased markers of myocardial injury, HW/BW ratio and randomized blood glucose compared to the control group, in addition to showing beneficial effects on mechanistic indices of myocardial oxidation, inflammation, apoptosis, and autophagy. Curcumin may exert cardioprotective effects in DCM through its antioxidant, anti-inflammatory, autophagy-enhancing, and anti-apoptotic effects. Modern studies have shown that curcumin can attenuate damage in DCM by being anti-inflammatory(Wei et al., 2023), anti-oxidative stress(Wu et al., 2022), anti-apoptosis(Ren et al., 2020), modulation of autophagy(Sadeghi et al., 2023), and anti-fibrotic(Wang et al., 2022). thus, curcumin emerges as a potential cardioprotective candidate for ameliorating DCM. Our results suggest that curcumin may play a cardioprotective 486 role in DCM through its antioxidant, anti-inflammatory, autophagy-enhancing, and anti-apoptotic effects.

Curcumin inhibits prostate cancer by upregulating miR-483-3p and inhibiting UBE2C
Journal of Biochemical and Molecular Toxicology | March 2024
Evidence has shown the efficacy of curcumin in inhibiting the progression of  prostate cancer. In this research, curcumin was found to suppress the proliferation and enhance the apoptotic rate in in vitro  prostate cancer cell models in a dose- and time-dependent manner.  In humans, the expression levels of UBE2C are significantly higher in  prostate cancer versus benign prostatic hyperplasia. Treatment with curcumin decreased the expression of UBE2C, whereas it increased miR-483-3p expression. In summary, curcumin exerts its antitumor effects through regulation of the miR-483-3p/UBE2C axis by decreasing UBE2C and increasing miR-483-3p. The findings may also provide new molecular markers for  prostate cancer diagnosis and treatment.

Curcumin and turmeric extract inhibit SARS-CoV-2 pseudovirus cell entry and spike-mediated cell fusion
bioRxiv | March 2024
Our study shows that turmeric extract and curcumin are potential inhibitors of SARS-CoV-2 infection at entry points, either by direct or indirect infection models. Curcumin has been tested for its anti-SARS-CoV-2 activities by plaque assay in Vero cells. Using the original virus, curcumin inhibits SARS-CoV-2 infection. Curcumin may inhibit SARS-CoV-2 viral replication as indicated by reduced N protein expression following viral infection. Here, we showed that curcumin and TE reduced PSV entry in331 293T/hACE2/TMPRSS2 cells, in which 10 μM curcumin and 10 μg/ml TE significantly affected the number of GFP dots. From the previous studies, Marin-Palma et al. reported that 10 μM curcumin can inhibit SARS-CoV-2 infection in Vero E6 cells. It is also reported that curcumin inhibits SARS-CoV-2 infection at concentrations of 3-10 μM.28. Furthermore, curcumin inhibited PSV339 entry in 293/hACE2 cells. These results corroborate curcumin effects against SARS-CoV-2340 infection with our data representing curcumin inhibition at PSV cell entry point. It has been known that curcumin affects the early stages of viral replication cycles, including viral-receptor attachment, internalization, and fusion that have been studied against several types of viruses which involve influenza, dengue, zika, chikungunya, pseudorabies, and VSV. Moreover, curcumin and TE inhibit secondary infection via cell-to-cell transmission in a syncytia formation model mediated by SARS-CoV-2 spike expression. Cells treated with curcumin and TE showed smaller syncytia with fewer nuclei than control cells. Curcumin can also interact with SARS-CoV-2 spike. These data align with our results that curcumin inhibited PSV350 entry and syncytia formation. Our in vitro study using PSV and syncytia models revealed that both curcumin and TE are potential inhibitors of SARS-CoV-2 infection. Curcumin can interfere with the spike-receptor binding during direct viral or  intercellular transmission, hindering viral infection and cell fusion.

Interleukin-4 from curcumin-activated OECs emerges as a central modulator for increasing M2 polarization of microglia/macrophage in OEC anti-inflammatory activity for functional repair of spinal cord injury
Cell Communication and Signaling | March 2024
Curcumin, a bioactive polyphenol extracted from rhizome of the Curcuma longa, possesses a variety of pharmacological and biological effects properties, such as anti-inflammatory, antioxidant, anticancer, immunomodulatory, autophagy-enhancing, and anti-microbial, etc. [34,35,36,37,38]. In addition to the reported benefits, numerous studies have shown that Curcumin exerts distinct neuroprotective and neutrophic effects on neuronal cells and glia by modulating their related signalling pathways [39,40,41]. Noteworthy, several recent reports have demonstrated that Curcumin can improve OEC proliferation, migration, morphologic changes, secretion of neurotrophic factors and phagocytic activity [29, 42]. That is, Curcumin significantly enhance the activation of OECs. In this regard, Curcumin potentiates the beneficial behavior of OECs including anti-inflammation and immunomodulation. As a result, aOECs could function as the most promising candidates for cell-based transplantation therapy targeting the CNS injury and neurodegenerative diseases.

Investigation of the role of curcumin against the toxicity induced by bisphenol a on the reproductive system in male rats
Journal of Kerbala for Agricultural Sciences | March 2024
The effect of curcumin as a protective role against BPA on the oxidative stress parameters showed that curcumin could decrease MDA concentration and at the same time increase the concentration of both catalase and SOD. Also, the results revealed that curcumin could increase the concentration of LH, FSH, and testosterone as compared to the BPA-treated group. Studies have demonstrated that curcumin effectively addresses several male reproductive problems, hence enhancing fertility. The positive benefits of curcumin may be attributed to its capacity to scavenge free radicals and function as an antioxidant agent, as well as its ability to elevate serum testosterone levels. Curcumin mitigated the impact of BPA and suppressed the antioxidant enzyme system in the host tissues. This resulted in a noteworthy decrease in MDA levels and a significant increase in catalase and SOD levels compared to the rats treated with BPA. Therefore, curcumin partially prevented the adverse effects caused by BPA. The presence of phenolic compounds in curcumin's structures is a crucial element in its ability to scavenge oxygen-derived free radicals that cause cell lipid peroxidation. Curcumin exhibits a protective impact on the enzymes SOD and CAT, which are reduced as a result of BPA induction. Additionally, curcumin decreases lipid peroxidation, specifically MDA. When curcumin is used together with other drugs, there is a considerable increase in antioxidant enzyme levels and a reduction in oxidative stress. Using Curcumin as an antioxidant to counteract the effects of BPA has a positive impact by effectively neutralizing the harmful free radicals and maintaining the sexual hormones at their optimal levels.

Efficacy and safety of curcumin therapy for knee osteoarthritis: A Bayesian network meta-analysis
Journal of Ethnopharmacology | March 2024
Compared with placebo, curcumin significantly reduced the visual analogue scale pain score and total WOMAC score. Compared with NSAIDs, curcumin and curcumin + NSAIDs had a reduced incidence of adverse reactions. The surface under the cumulative ranking curve results indicated that curcumin monotherapy, curcumin + chondroprotective agents, and curcumin + NSAIDs have good clinical value in osteoarthritis treatment. Curcumin, either alone or in combination with other treatments, is considered to have good clinical efficacy and safety in osteoarthritis treatment. Drug combinations containing curcumin may have the dual effect of enhancing efficacy and reducing adverse reactions. Curcumin has anti-inflammatory, antitumour, antioxidant, lipid-regulating, anticoagulant and other pharmacological effects (Benameur et al., 2023; Luo et al., 2023; Moballegh Nasery et al., 2020; Zhang et al., 2018). Curcumin is a bioactive natural substance with great potential clinical application value and is widely used in traditional Chinese medicine to treat osteoarthritis and rheumatoid arthritis (Akaberi et al., 2021; Feng et al., 2022; Henrotin et al., 2022). Curcumin has anti-inflammatory and analgesic effects similar to those of NSAIDs for arthritis and has a lower incidence of adverse reactions (Chopra et al., 2013). Curcumin is believed to exert an anti-inflammatory effect by inhibiting the biological activity and synthesis of important proteases that mediate the inflammatory process, such as cyclooxygenase-2, lipoxygenase and inducible nitric oxide synthase (iNOS) (Paulino et al., 2016). In addition, curcumin is believed to protect cartilage (Comblain et al., 2016; Liu et al., 2018). Prior to the current work, some clinical studies preliminarily confirmed the clinical efficacy of curcumin in the treatment of arthritis (Atabaki et al., 2020; Jamali et al., 2020). There are also traditional head-to-head meta-analyses in the literature that provide further evidentiary support for treating arthritis with curcumin (Feng et al., 2022; Wang et al., 2021). In terms of reducing RM use, curcumin, curcumin + NSAIDs and NSAIDs are better than placebo, and curcumin + NSAIDs are better than NSAIDs alone. These results indicate that the use of curcumin may reduce the total amount of analgesic drugs used by knee osteoarthritis patients. In terms of the incidence of adverse reactions, both curcumin and curcumin + NSAIDs were lower than NSAIDs alone. The results found that curcumin, curcumin + CP, and curcumin + NSAIDs have good clinical value in treating knee osteoarthritis. The results of SUCRA indicate that the two best treatment measures for reducing VAS pain scores are curcumin and curcumin + CP. Curcumin and NSAIDs are the preferred options for reducing the total WOMAC score. Curcumin + NSAIDs is the best medication for reducing the use of RM. Curcumin + NSAIDs and curcumin + CP are the best two drug regimens for reducing the incidence of AE. The above results suggest that curcumin can not only have better clinical efficacy in the treatment of knee osteoarthritis but also reduce the incidence of AE by its combination with NSAIDs, but this situation still needs more clinical data for verification. The conclusion of this NMA will provide a new perspective for clinical decision-making on the use of curcumin in the treatment of KOA, and we believe that the combination of curcumin with other drugs should be studied further. Experimental research (Guan et al., 2022; Hamdalla et al., 2022; Zhang and Zeng, 2019) suggests that curcumin has a good effect in the treatment of knee osteoarthritis, which can promote chondrocyte proliferation, inhibit chondrocyte apoptosis, inhibit the destruction of inflammatory factors on cartilage, and maintain the balance of the internal environment of articular cartilage. Shakibaei et al. found that curcumin can inhibit the expression of MMP-3 and MMP-9 induced by IL-1β/TNF-α in human chondrocytes (Shakibaei et al., 2007), which indicates that curcumin can inhibit the decomposition of cartilage matrix and play a role in treating KOA. The experiment with human chondrocytes as the research object shows that curcumin can downregulate the expression of inflammatory factors in cells, such as nitric oxide, prostaglandin 2, TNF-a, IL-6, and IL-8, reduce cartilage inflammation, and then inhibit cartilage damage (Crivelli et al., 2019; Kim and Kim, 2019). In this context, combined with our NMA results, we believe that curcumin has great clinical application value in the treatment of knee osteoarthritis and may become a substitute for NSAIDs.

Therapeutic advantages of curcumin, a polyphenol, against traumatic brain injury through interaction with different inflammatory signaling pathways and their effects on levels of cytokines and related biomarkers
 Molecular Neurobiology | March 2024
The recent findings on curcumin demonstrate its remarkable versatility as a molecule that interacts with a variety of molecular targets. Various central nervous system disease models have been shown to be susceptible to curcumin's anti-inflammatory properties, including intracerebral hemorrhage, global brain ischemia, and neurodegeneration, all of which are associated with the inflammation of the central nervous system. Similarly, curcumin exerts neuroprotective effects in mammals when it crosses the blood–brain barrier. Curcumin has been shown to reduce cerebral edema, enhance membrane and energy homeostasis, and influence synaptic plasticity following traumatic brain injury in studies. Curcumin has been shown by numerous studies to be effective in reducing inflammation. Research has shown that curcumin suppresses the activation of NF-κB by inhibiting the phosphorylation and degradation of IκB; as a result, curcumin reduces the inflammation caused by NF-κB. The effects of curcumin have been shown to be not only reduced post-traumatic brain injury neuroinflammation, but also decreased levels of inflammatory mediators that are produced following a traumatic brain injury. The anti-inflammatory effects of curcumin were demonstrated in an in vitro study using 100 mg/kg of curcumin. According to the report, curcumin was able to reduce the amounts of damage after traumatic brain injury induction and apoptosis, particularly in the cortical cell model derived from embryonic 15-day pregnant mice, resulting in reduced damage. One study in rats with traumatic brain injury administered 30 and 50 mg/kg of curcumin daily for 35 days reduced levels of NLRP3, IL-1β, IL-6, IL-18, and TNF-α. There was a reduction in neuroinflammation and subsequent complications of TBI when curcumin was administered. Furthermore, curcumin (at 500 mg/kg/day) decreased injury in the ipsilateral cortex as a result of its ability to enhance neutrophil infiltration (weight drop model-TBI). Curcumin reduced apoptosis in cells and increased antioxidant activity, suggesting potential neuroprotective effects. The pain levels decreased when curcumin (50 mg/kg) was administered to surgically induced traumatic brain injury rats. Curcumin has been found to inhibit non-selective histone acetyltransferases, suggesting potential benefits through histone acetylation. In a rat model of TBI induced by FPI, curcumin (100 mg/kg) exerted neuroprotective properties by activating the Nrf2 pathway. BDNF, synapsin I, and CREB levels were reduced in animal models following TBI after curcumin treatment (500 ppm). When given oral doses of 100 mg/kg of curcumin per day, oxidative damage was decreased, and omega-3 fatty acid DHA levels and 4-HNE (an indicator of membrane lipid peroxidation) increased. Curcumin supplements may have neuroprotective effects after brain injury and may increase the activity of docosahexaenoic acid and fatty acid-transport protein. According to Sharma et al.'s study published in 2010, curcumin reduced iPLA2, 4-HNE, and STX-3, which improved learning progress and relieved complications associated with traumatic brain injury. Several studies, such as the one by Zahedi et al., suggest promising effects of curcumin, developing effective therapeutic strategies necessitates rigorous preclinical studies and clinical trials.

Curcumin mitigates acrylamide-induced ovarian antioxidant disruption and apoptosis in female Balb/c mice: A comprehensive study on gene and protein expressions
Food Science & Nutrition | March 2024
Curcumin is known for its antioxidant properties.Evidence has shown that curcumin exhibits anti-inflammatory, antioxidants, anti-cancer activities (Khajeh pour et al., 2023; Mailafiya et al., 2023). These advantageous features are attributed to its elevated antioxidant activity, stemming from the hydroxyl and methylene groups within the β-diketone moiety present in its chemical structure (Chen et al., 2023; Wang et al., 2017). There are several studies that explored the positive effects of curcumin on the ovary tissue. Azami et al. (2020) showed that curcumin could prevent ovarian aging by increasing ovarian volume and the number of follicles. Lv et al. (2021) also suggested that curcumin had beneficial effects on the ovary and reproductive organs by regulating the PTEN-AKT-FOXO3a pathway. Furthermore, ACR exposure led to a significant increase in estradiol, luteinizing hormone, testosterone, ovarian tumor markers such as CA125, and carcinoembryonic antigen (CEA), while serum progesterone, follicle-stimulating hormone, and total antioxidant capacity decreased in female rats. Curcumin treatment restored serological indices toward normal levels (Elsawi et al., 2023). In our study, ACR exposure adversely affected ovarian antioxidant defense thereby leading to increased pro-apoptotic markers. Notably, curcumin treatment effectively mitigated these effects, restored antioxidant potential, and reduced acrylamide-induced toxicity in female mouse ovaries. Our findings indicate that the administration of curcumin at doses of 100 and 200 mg/kg efficiently restores the expression of antioxidant genes, demonstrating a significant improvement at the 200 mg/kg dose compared to the 100 mg/kg dose. Several studies have illustrated the efficacy of curcumin in mitigating oxidative stress-related concerns, encompassing factors like total antioxidant capacity, malondialdehyde (MDA), and superoxide dismutase (SOD) within physiological conditions (Chen et al., 2022; Khayatan et al., 2023). In a recent systematic review and meta-analysis of randomized controlled trials, curcumin exhibited a substantial influence on indicators of oxidative stress, including total antioxidant capacity, malondialdehyde, and SOD levels (Dehzad et al., 2023). In various animal models of ovarian diseases, curcumin has demonstrated the ability to enhance overall ovarian function (Eser et al., 2015; Wang et al., 2017). Furthermore, the administration of curcumin has been proven beneficial in addressing gynecological diseases in women, as highlighted in studies (Kamal et al., 2021; Shen et al., 2022). For instance, curcumin supplementation has beneficial effects on weight loss, glucose and lipid metabolism, metabolic parameters, and androgen levels in polycystic ovary syndrome patients (Ghanbarzadeh-Ghashti et al., 2023; Sohaei et al., 2019). Curcumin causes a reduction in serum nitric oxide release in women with primary dysmenorrhea and premenstrual syndrome pain (Farrokhfall et al., 2023). It also decreases the total score of primary symptoms of menopause by affecting oxidative Stress Biomarkers (Farshbaf-Khalili et al., 2022). Importantly, curcumin treatment emerged as a promising therapeutic intervention, effectively restoring antioxidant potential and mitigating acrylamide-induced toxicity in the ovaries of female mice. These results contribute to a deeper understanding of the molecular mechanisms involved in ACR-induced reproductive toxicity and underscore the potential of curcumin as a protective agent against such detrimental effects.

Curcumin abrogates cobalt-induced neuroinflammation by suppressing proinflammatory cytokines release, inhibiting microgliosis and modulation of ERK/MAPK signaling pathway.
Journal of Chemical Neuroanatomy | March 2024
Curcumin treatment significantly reduced tissue levels of proinflammatory cytokines TNF-α and IL-1β. Microglial activation and ERK protein upregulation induced by cobalt were attenuated by curcumin. Results showed that curcumin abrogated neuroinflammation by suppressing the release of proinflammatory biomarkers, reducing microgliosis, and modulating the ERK MAPK pathway. Extensive studies have suggested that curcumin possesses anti-inflammatory (Wang et al., 2017), neuroprotective (Teter et al., 2019), antioxidant (Memarzia et al., 2021), anti-cancer (Dou et al., 2017), hepatoprotective (Macías-Pérez et al., 2019). Curcumin significantly suppressed the release of neuroinflammation markers and reduced microgliosis in the hippocampus of the rats. In addition, the significant correlation between ERK expression and proinflammatory biomarkers and microgliosis has offered some mechanistic insight into curcumin's neuroprotective properties.

Curcumin in Cancer and Inflammation: An In-Depth Exploration of Molecular Interactions, Therapeutic Potentials, and the Role in Disease Management
International Journal of Molecular Sciences | March 2024
Curcumin, a polyphenolic compound, is extracted from the turmeric plant. The significance of curcumin’s structure, especially its conjugated enol-ketone system, lies in its ability to engage in diverse molecular interactions. In colorectal cancer, early studies indicated potential benefits of curcumin in reducing polyp number and size in familial adenomatous polyposis (FAP) patients, suggesting its role in managing precancerous lesions. For head and neck cancer, particularly oral leukoplakia, curcumin showed a significant clinical response compared to placebo. It is also noteworthy that the combination of clinical and histological responses indicated a more pronounced effect of curcumin, suggesting its potential utility in the early-stage management of oral leukoplakia. In the context of multiple myeloma, particularly in patients with monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM), curcumin demonstrated some promise. The promising results in certain areas warrant continued research to optimize curcumin’s formulation, delivery, and dosing to maximize its clinical benefits.

Curcumin effects on glycemic indices, lipid profile, blood pressure, inflammatory markers and anthropometric measurements of non-alcoholic fatty liver disease patients: A systematic review and meta-analysis of randomized clinical trial
Complementary Therapies in Medicine Volume | March 2024
Curcumin supplementation was associated with significant changes in fasting blood glucose and homeostatic model assessment for insulin resistance in adults with NAFLD. Curcumin supplementation was associated with significant changes in triglyceride, total cholesterol, and low density lipoprotein in adults with NAFLD. Curcumin supplementation in doses of 50−3000 mg/day over 8–12 weeks was associated with significant reductions in levels of FBG, HOMA-IR, TG, TC, LDL, weight and BMI in patients with NAFLD. Previous studies have reported curcumin as a safe complementary therapy for several diseases. A systematic review suggested that curcumin is effective in lowering low density lipoprotein, cholesterol (LDL-C), TG, fasting blood glucose (FBG), homeostatic model assessment for insulin resistance (HOMA-IR), and weight in NAFLD patients, and it is well tolerated. Another study revealed that curcumin supplementation has favorable effects on metabolic markers and anthropometric parameters in patients with NAFLD.  Also, results of a randomized controlled trial suggest that curcumin supplementation reduces serum lipids in patients with NAFLD.  A study showed curcumin supplementation has a favourable effect on total cholesterol (TC), and BMI in participants with NAFLD. Therefore, promoting curcumin as adjuvant treatment on NAFLD patients might be justified. In conclusion, our study indicated that curcumin supplementation in doses of 50 − 3000 mg/day over 8–12 weeks was associated with significant changes in FBG, HOMA-IR, TG, TC, LDL, weight and BMI in adults with NAFLD.

Curcumin suppresses metastasis of triple-negative breast cancer cells by modulating EMT signaling pathways: An integrated study of bioinformatics analysis
Medicine | February 2024
Curcumin demonstrates potential anticancer properties in the treatment of triple-negative breast cancer cells. The findings suggest that the inhibitory effect of curcumin on the motility of triple-negative breast cancer cells could be attributed to the concurrent downregulation of specific signaling pathways, through influencing the EMT signaling process. This study employs a comprehensive approach that integrates bioinformatics analysis with in vitro experimental methodologies, providing substantial evidence supporting curcumin’s potential in breast cancer therapy. Curcumin exhibits its therapeutic potential in triple-negative breast cancer cells by modulating multiple signaling pathways. These findings provide experimental evidence for considering curcumin as a potential therapeutic strategy in the treatment of triple-negative breast cancer cells. This study concentrates on curcumin, a yellow phenolic pigment derived from turmeric, renowned for its anti-inflammatory, antioxidant, and immunomodulatory properties. Recent research has shown that curcumin is crucial in treating several tumors by modulating typical cell biological effects such as cell proliferation, apoptosis, cell cycle, and metastasis. Thus, curcumin may play a significant role in the initiation and progression of various cancers, including breast, lung, and liver cancers, through affecting multiple signaling and molecular pathways, such as Rb, P53, mitogen-activated protein kinase, phosphatidylinositol 3-K (PI3K)/protein kinase B, and NF-kappaB (nuclear factor kappa B cells, NF-κB). Previous studies have demonstrated curcumin’s capacity to inhibit cell proliferation and invasion in human triple-negative breast cancer cells. This study is significant for its exploration of curcumin’s potential clinical applications in treating triple-negative breast cancer cells. By elucidating the antitumor mechanisms of curcumin in TNBC cells, it establishes a crucial foundation for developing innovative therapeutic strategies. Curcumin significantly inhibited the proliferation of Hs578T and MDA-MB-231 cells. Flow cytometry results showed that curcumin induced apoptosis in these cells and arrested the cell cycle at the G2/M phase. Additionally, Transwell assay results showed that curcumin effectively reduced the motility of Hs578T and MDA-MB-231 cells. Enrichment analysis of RNA sequencing data showed that the mechanism of action of curcumin was significantly associated with signaling pathways such as pathways in cancer, focal adhesion, and PI3K-Akt signaling pathways. Finally, Western blotting analysis showed that curcumin significantly decreased the expression levels of key proteins including Fibronectin, mTOR, β-Catenin, p-Akt, Akt, N-Cadherin, p-S6, and S6.  Curcumin, an efficacious anticancer compound isolated from turmeric rhizomes, mediates its therapeutic effects through the modulation of various cellular pathways. These include the suppression of tumor metastasis, angiogenesis, and inflammation, alongside the modulation of apoptosis, cell cycle progression, and resistance to multiple drugs. The role of curcumin as a cancer chemopreventive agent has been rigorously studied in various cancer models. Recent studies have highlighted curcumin’s antiproliferative and antimotility effects on breast cancer cells. In this study, our objective is to elucidate the antitumor properties of curcumin, focusing on its potential mechanisms of action and therapeutic efficacy. Employing gene enrichment analysis, incorporating both Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways, on RNA sequencing data, we determined that curcumin predominantly acts through pathways such as Pathways in cancer, Focal adhesion, PI3K-Akt signaling pathway, and cell cycle. he CCK8 assay indicated that curcumin markedly reduces the cellular activity of TNBC cells. In parallel, Western Blot analysis revealed that curcumin lowers the expression of key proteins, including N-Cadherin, Fibronectin, β-Catenin, p-Akt, Akt, mTOR, p-S6, and S6, in Hs578T and MDA-MB-231 cells. These proteins play crucial roles in the EMT process and its related signaling pathways, particularly the PI3K/Akt/mTOR pathway. The results imply that curcumin’s inhibitory effect on the motility of triple-negative breast cancer cells may stem from the simultaneous downregulation of these signaling pathways, impacting the EMT signaling cascade.

Curcumin Enhances the Anti-Cancer Efficacy of CDK4/6 Inhibitors in Prostate Cancer
Archivos Españoles de Urología | February 2024
This study aimed to investigate the potential of combining cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors with curcumin, a natural compound known for its anti-aging properties, to enhance the anti-cancer efficacy in prostate cancer. Curcumin is a natural compound extracted from turmeric, which has been shown to have multiple biological activities, including anti-inflammatory, antioxidant and anti-cancer effects. The synergistic effect observed in this study suggested that curcumin may enhance the therapeutic efficacy of CDK4/6 inhibitors in prostate cancer treatment, further proving the previously reported findings. Furthermore, this study revealed that curcumin regulated cellular aging induced by CDK4/6 inhibitors through the inhibition of the mTOR and STAT3 pathways, which was also reported in previous studies. Similar conclusions were drawn in this study, which showed that curcumin could modulate cellular senescence. Interestingly, curcumin contributed to the anti-cancer effects of CDK4/6 inhibitors in prostate cancer treatment. Moreover, this study revealed that curcumin could inhibit the stemness characteristics of cancer cells induced by LY CM, as evidenced by the downregulation of cancer stem cell markers ALDH1A1, CD44 and Nanog. The ability of curcumin to target cancer stem cells provides further evidence of its potential as an effective therapeutic agent in prostate cancer treatment. As previously reported, the combination of curcumin and LY CM can inhibit the dryness of cancer cells. Overall, the findings of this study support the notion that combining CDK4/6 inhibitors with curcumin may have clinical implications for the treatment of prostate cancer. The findings of this study provide valuable insights into the potential of combining CDK4/6 inhibitors with curcumin in the treatment of prostate cancer.

The complex effect of polyphenols on the gut microbiota and triggers of neurodegeneration in Parkinson’s disease
Zhurnal Nevrologii  | February 2024
A promising direction for influencing microflora and inflammatory changes in the intestine is the use of polyphenols, primarily curcumin. The review of experimental, laboratory, clinical research proving the pleiotropic effect of curcumin, including its antioxidant, anti-inflammatory, neuroprotective effects, realized both through peripheral and central mechanisms is presented.

Immunomodulatory effects of curcumin on macrophage polarization in rheumatoid arthritis
Frontiers in Pharmacology | February 2024
As a natural compound, curcumin is favorable for improving symptoms in rheumatoid arthritis patients due to its potent efficacy, affordability, and minimal side effects. In addition, curcumin has been reported to ameliorate several diseases via epigenetic regulation, encompassing: (1) suppression of DNMTs; (2) regulation of histone acetyltransferases and histone deacetylases; and (3) regulation of miRNAs (Boyanapalli and Kong, 2015). Several studies have shown that curcumin can be used in cancer treatment to reverse DNA methylation, alter histone modifications and target miRNA expression (Shu et al., 2011; Bao et al., 2012; Yu et al., 2013). Curcumin has been extensively demonstrated to possess anti-inflammatory, antioxidant, immunomodulatory and anticancer properties in both experimental and clinical studies (Xu et al., 2018). Curcumin has shown strong therapeutic potential, especially in autoimmune diseases, such as RA and systemic lupus erythematosus (SLE) (Yang et al., 2019; Chamani et al., 2022; Kou et al., 2023). A large number of investigations have indicated that curcumin modulates macrophage polarization and function to alleviate inflammation and therefore can be used to treat inflammation-related diseases (Gao et al., 2015; Karuppagounder et al., 2016; Abdollahi et al., 2023). Curcumin regulates the functions of various immune cells, including macrophages (Mohammadi et al., 2019), dendritic cells (DCs) (Rahimi et al., 2021), B cells (Mohammadi et al., 2022) and T cells (Rahimi et al., 2019), thereby modulating both innate and adaptive immunity (Shehzad and Lee, 2013). The anti-inflammatory activity of curcumin is due to its suppression of multiple signalling molecules, including NF-κB, activated protein (AP)-1, MAPKs, and protein kinase C (Kahkhaie et al., 2019). In addition, curcumin is a potent inhibitor of reactive-oxygen-generating enzymes, such as lipoxygenase, cyclooxygenase (COX), xanthine dehydrogenase and iNOS (Rao, 2007). As shown in macrophages, curcumin inhibits LPS and IFN-γ-induced nitric oxide production.

Curcumin mediated dendritic cell maturation by modulating cancer associated fibroblasts
Journal of Cancer Research and Therapeutics | February 2024
Curcumin, traditionally known for its anti-inflammatory effects, has been shown to be a potent immunomodulatory agent that can modulate the activation of various immune cells by downregulating pro-inflammatory cytokines, including IL-1, IL-2, IL-6, IL-8, IL-12. In our previous studies, we have reported on curcumin's different potential to target cancerous cells in Acute myeloid leukemic (AML) patients as well as lung cancer patients.  Moreover, several reports have suggested that curcumin-treated DCs produce significantly lower levels of IL-6, IL-12, IL-10, and TNFα, thus creating a Th2 permissive environment. In addition, there are several other reports confirmed that curcumin inhibited IL-1b, IL-6 through modulation of NF-kB and MAPK pathways. Moreover, curcumin-inhibited IL-6-induced STAT3 phosphorylation and nuclear translocation in multiple myeloma cells. Recently, Paul S and Sa G revealed that curcumin acting as an adjuvant in immunotherapies may present with novel approaches for researchers and clinicians to obtain improved treatment outcomes. Collectively, our results concur with previous findings reported by other researchers, signifying curcumin’s potential to decrease the secretion of IL-6, IL-10, and TGF-β in conditioned media, this being mediated via curcumin’s efficacy to instruct cancer associated fibroblasts to secrete exosomes resulting in the creation of an immunomodulating TME from an immunosuppressive TME environment. This study may provide basis to revise fundamental treatment rationales and formulate synergistic therapeutic approaches by using curcumin along with DC-based immunotherapies to overcome cellular resistance in cancer treatment but it still requires more in-depth research to have an in-sight into mechanism, which might open up a newer avenues for curcumin’s use as an appropriate immunotherapeutic modulator.

Exploring the therapeutic potential of curcumin in oral squamous cell carcinoma
Pathology - Research and Practice | February 2024
Curcumin, a polyphenolic compound derived from rhizomes of Curcuma longa (turmeric), has garnered significant attention due to its potential as an anticancer agent. Its pleiotropic properties, including anti-inflammatory, antioxidant, and anti-tumor activity, make it a compelling candidate for exploring novel strategies in the oral cancer treatment. Of particular interest is curcumin’s capacity to interfere with the intricate web of cellular signaling pathways involved in angiogenesis and tumor progression. Our study highlights the intriguing possibility of curcumin being a multifaceted medicinal supplement in the fight against oral cancer. Through its modulation of HIF-1α, VEFG, STAT3, and MMP-3, curcumin shows promise in disrupting critical pathways associated with angiogenesis and tumor progression, offering new avenues for targeted cancer treatments. These findings underscore curcumin’s significance in oral cancer research and its potential for future clinical applications.

Curcumin in Alzheimer’s Disease and Depression: Therapeutic Potential and Mechanisms of Action
Brazilian Archives of Biology and Technology | February 2024
Curcumin is a polyphenol present in Curcuma longa, a root used in Asian cuisine for thousands of years, and it has several medicinal properties, acting as an antioxidant, anti-inflammatory, anticancer, among others. The aim of this study was to evaluate the effects of curcumin in Alzheimer's disease and Depression, which has as its main pathogenesis the reduction of BDNF levels, monoamine levels, increased oxidative stress, inflammation, beta-amyloid aggregation, Tau protein accumulation and aluminum neurotoxicity, verifying its therapeutic capacity. Therefore, a literature review was performed in the Scholar Google, ScienceDirect, and PubMed databases. The data analyzed demonstrated that curcumin supplementation is able to restore BDNF levels in Alzheimer's disease and depression, in addition to modulating monoamines and reducing oxidative stress, inflammation, beta-amyloid aggregation, Tau protein accumulation and aluminum neurotoxicity, improving their symptoms.

The Protective Effects of Curcumin against Renal Toxicity
Current Medicinal Chemistry | February 2024
Curcumin is a naturally polyphenolic compound used for hepatoprotective, thrombosuppressive, neuroprotective, cardioprotective, antineoplastic, antiproliferative, hypoglycemic, and antiarthritic effects. Kidney disease is a major public health problem associated with severe clinical complications worldwide. The protective effects of curcumin against nephrotoxicity have been evaluated in several experimental models. In this review, we discussed how curcumin exerts its protective effect against renal toxicity and also illustrated the mechanisms of action such as anti-inflammatory, antioxidant, regulating cell death, and anti-fibrotic. This provides new perspectives and directions for the clinical guidance and molecular mechanisms for the treatment of renal diseases by curcumin.

Effect of Curcumin on the Process of Neuroinflammation Caused by COVID-19
Curcumin and Neurodegenerative Diseases | February 2024
Curcumin, the main active ingredient of Curcuma longa L., has antioxidant, anti-inflammatory, antitumor, antiviral, neuroprotective, and immune system-modulating properties. Because of these properties, this curcuminoid may be helpful both before and after SARS-CoV-2 infections, enhancing health status in the various complications brought on by the illness (respiratory, enteric, hepatic, and neurological). From this perspective, this chapter aims to report on findings regarding the effect of turmeric on COVID-19-induced neuroinflammation. Some studies highlight that curcumin is effective in COVID-19 conditions by inhibiting inflammatory and neuroinflammatory signaling pathways, such as nuclear factor kappa B (NF-kB), and the induction of various pro-inflammatory cytokines and chemokines, including interleukin (IL)-6, interferon (IFN) γ, monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α and IL-1β.

Effect of Curcumin on Dysmenorrhea and Symptoms of Premenstrual Syndrome: A Systematic Review and Meta-Analysis
Korean Journal of Family Medicine | February 2024
The reduction in the severity of PMS and dysmenorrhea has been attributed to curcumin’s anti-inflammatory and antidepressant activities. Studies have found that curcumin can alleviate symptoms of dysmenorrhea and PMS. Evidence shows that curcumin has pleiotropic effects and acts as an anti-inflammatory, anticancer, antioxidant, and antibacterial agent. In addition, curcumin can reduce prostaglandin production. Khayat et al.found that curcumin can alleviate symptoms experienced before menstruation without any adverse effects. Furthermore, curcumin in women with PMS may also regulate neurotransmitters and biomolecules, exert antioxidant and analgesic effects, and reduce oxidative stress. In conclusion, the findings of our meta-analysis showed that using various forms of curcumin could reduce the severity of PMS and dysmenorrhea owing to its anti-inflammatory and antidepressant activities. The present study revealed that curcumin consumption immediately before or during menstruation could alleviate the severity of dysmenorrhea. Therefore, it could be regarded as an appropriate alternative for women with PMS and dysmenorrhea to improve their quality of life.

Review of the Protective Mechanism of Curcumin on Cardiovascular Disease
Drug Design, Development and Therapy | February 2024
Curcumin has been shown to have a variety of pharmacological properties over the past decades. Curcumin can significantly protect cardiomyocyte injury after ischemia and hypoxia, inhibit myocardial hypertrophy and fibrosis, improve ventricular remodeling, reduce drug-induced myocardial injury, improve diabetic cardiomyopathy(DCM), alleviate vascular endothelial dysfunction, inhibit foam cell formation, and reduce vascular smooth muscle cells (VSMCs) proliferation. Clinical studies have shown that curcumin has a protective effect on blood vessels. Toxicological studies have shown that curcumin is safe.  Curcumin is a bioactive component of the curry spice, and its pleiotropic effects in cardiovascular diseases suggest that it is a promising drug candidate. Specifically, curcumin can significantly alleviate vascular endothelial dysfunction, inhibit foam cell formation, reduce VSMCs proliferation, protect cardiomyocyte injury after ischemia and hypoxia, inhibit myocardial hypertrophy and fibrosis, improve ventricular remodeling, reduce drug-induced myocardial injury, and improve DCM. The therapeutic effect and mechanism of curcumin have become the focus of pharmacokinetic research. Curcumin has a good therapeutic effect, especially in the cardiovascular field. Previous reviews have summarized the protective effects of curcumin on CVDs. In 2020, Li et al reviewed the preclinical studies of curcumin in CVDs such as cardiac hypertrophy, heart failure, abdominal aortic aneurysm, stroke, drug-induced cardiotoxicity, and diabetic cardiovascular complications, and reviewed the potential molecular targets of curcumin. Pourbagher-Shahri et al also reviewed the effects of curcumin on the cardiovascular system in 2021. The protective mechanism of curcumin against cardiovascular diseases is complex and networked. It is important to note that curcumin is a complementary or alternative medicine, not a replacement for the main treatment, and needs to be used under the guidance of a doctor. To be sure, curcumin is an important drug that is worth exploring.

Curcumin alleviates atrazine-induced cardiotoxicity by inhibiting endoplasmic reticulum stress-mediated apoptosis in mice through ATF6/Chop/Bcl-2 signaling pathway
Biomedicine & Pharmacotherapy | February 2024
Curcumin displays promise in alleviating heart injury by alleviating cardiac apoptosis.  Curcumin, acclaimed for its pronounced anti-inflammatory and antioxidant properties, has garnered interest as a potential therapeutic agent. Collectively, our findings illuminate curcumin’s cardioprotective effect against ATR-induced injury, primarily through its anti-ERS and anti-apoptotic activities, underscoring curcumin’s potential as a therapeutic for ATR-induced cardiotoxicity. Curcumin has many biological benefits, such as antioxidant, anti-inflammation and immunoregulatory effect. Research has shown that curcumin can help reduce damage to various systems in the body, such as the cardiovascular, digestive, and respiratory systems. In addition, adding the curcumin to the diet can significantly reduce the body weight and body fat rate of mice which fed with high-energy diet, and alleviate inflammation and diabetes in mice. Meanwhile, curcumin significantly decreased the expression of inflammatory factors induced by tumor necrosis factor-α in adipocytes and the differentiation of preadipocytes. Mortezaee and his colleague’s study shown that curcumin inhibits the growth of tumor cells. Curcumin has various pharmacological effects, including reducing inflammatory reactions and oxidative stress, enhancing immunity, and combating infections. Recent studies have shown that the cardioprotective benefits of curcumin are facilitated through myriad mechanisms, among which include the modification of gut microbiota makeup, inducement of macrophage polarization, alleviation of oxidative stress, and modulation of pivotal signaling pathways such as AMPK and mTOR. In doing so, curcumin minimizes damage to the subcellular structures within the myocardium. The present study revealed that curcumin can alleviate the ATR-induced damage in cardiac cells. This mitigation manifests as reductions in inflammatory cell infiltration and subcellular membrane damage (including mitochondria, endoplasmic reticulum, and nucleus) instigated by ATR. Most notably, curcumin appears to have the capacity to remediate myocardial damage.

Improving cognitive function with intermittent dose escalation of curcumin extract in chemotherapy-induced cognitive impairment patients: a randomized controlled trial
Advances in Traditional Medicine | February 2024
The group of subjects receiving curcumin extract experienced clinically and statistically significant improvements in cognitive function. Administration of curcumin extract with intermittent dose escalation regimen proved to be safe and able to improve cognitive function of cognitive impairment patients clinically and statistically significant. Recently, there has been multiple pharmacological studies done to investigate the antioxidant, antiinflamation, anticarcinogenic, and anti-bacterial effects of curcumin. Curcumin is a safe natural product to be consumed by humans (Abd El-Hack et al. 2021). Curcumin is also known to increase the effectiveness of chemotherapeutic agents via increasing cancer cells sensitization against chemotherapy and protecting normal cells from chemotherapy damage (Tan and Norhaizan 2019). Curcumin extract has several advantages, including having a pleiotropic effect as anti-inflammatory, antioxidant, and antiapoptotic (Panahi et al. 2021; Abd El-Hack et al. 2021). Furthermore, curcumin extract also has anti-carcinogenic effects. Thus, the combination of various mechanisms of action makes curcumin extract a comprehensive therapeutic modality to prevent or treat cellular damage, especially due to exposure to neurotoxic and oxidative stress chemotherapeutic agents (Liu et al. 2019; Akbari et al. 2020). In addition, curcumin extract also has a low toxicity index, so it has a broad and safe therapeutic window profile. Clinically, curcumin extract has been widely tested and is known to have neuroprotective effects. For example, curcumin extract can inhibit cognitive function impairment caused by the oxidative stress of cigarette smoke (Muthuraman et al. 2019). In the context of chemotherapy, curcumin has been shown to improve neurogenesis and synaptogenesis that play a role in brain plasticity, as well as increase hippocampal autophagy so that it can suppress the process of apoptosis in the central nervous system, after exposure to cisplatin-based chemotherapy (Yi et al. 2020). Thus, administration of curcumin extract in carcinoma patients undergoing chemotherapy regimens can help prevent, even improve, the symptoms of cognitive impairment. Based on the results of the analysis of this study, valid evidence was found that the administration of curcumin extract with the new regimen was proven to be safe and effective in improving cognitive function in patients with cognitive impairment due to carboplatin-paclitaxel chemotherapy regimen.  Administration of curcumin extract with a dose escalation system was proven to improve cognitive function of patients with clinical and statistical significance. Administration of curcumin extract with this dosage regimen has also been shown to have a good safety profile.

A Review on Medicinal Benefits of Curcumin on Cancer
International Research Journal of Modernization in Engineering Technology and Science | February 2024
Curcumin, a natural polyphenol found in the food spice turmeric, has been shown to inhibit the survival and proliferation of cancer cells and trigger apoptosis without promoting side effects. In this context, the regulation of the cell cycle and its modulation by curcumin has attracted great attention in recent years. Curcumin can inhibit cancer cells, cause apoptosis, inhibit angiogenesis, inhibit the expression of anti-apoptotic proteins, as well as inhibit the immune system of cancer cells. Various studies have reported the antitumor activity of curcumin against breast cancer, lung cancer, head and neck squamous cell carcinoma, prostate cancer, and brain tumors. Curcumin and its derivatives have attracted great attention in the last two decades due to their biofunctional properties such as antibacterial, antifungal and antiviral. Curcumin exerts its anti-cancer effect through various mechanisms. Curcumin can inhibit the growth of many cancer cells by reducing the regulation of anti-apoptotic cells, activating caspases, and promoting tumor suppressors such as P53. Curcumin has properties that scavenge free radicals and therefore may play an important role in inhibiting the growth of cancer. Many cellular and preclinical studies have shown that curcumin can prevent DNA damage caused by oxidative factors (such as ionizing radiation) by inhibiting free radicals and reactive oxygen species. Curcumin prevents cancer formation by inhibiting the formation of NF-kappaB. Curcumin prevents tumor formation and growth by inhibiting and activating two enzymes (Phase 1 and Phase 2).  The motivation to use curcumin stems not only from its therapeutic potential, but also from the fact that curcumin is more easily absorbed by patients without the side effects of many other medicinal products such as nausea, vomiting, diarrhea, hair lossand more serious long-term conditions such as liver failure. Various studies comparing breast cancer incidence and cancer rates in India and the West show that the risk of breast cancer is lower in India. Curcumin can interact with various biochemical pathways of cancer cells and survive by directly or indirectly binding to different targets. Curcumin has been shown to interact with many targets, including transcription factors, growth factors, DNA, RNA, and many proteins involved in cell signaling pathways. The chemical structure of curcumin has diverse properties that make it highly effective and has many synergistic properties for various molecular targets. Curcumin, the active ingredient of turmeric extract, has been used for many years as anti-inflammatory, antioxidant, anti-cancer and more. Although there is much to learn about curcumin and its therapeutic properties, it has great potential in the treatment and prevention of cancer. Curcumin, a natural product, is not only non-toxic but also has many effects on various pathways involved in tumorigenesis.

Curcumin Improves Chemotherapy Resistance in Breast Cancer Cells via Inhibiting the Secretion of FGF2/FGFR2 from Cancer-Associated Fibroblasts
Journal of Biological Regulators and Homeostatic Agents | February 2024
In this experiment, the data also showed that curcumin effectively blocked breast cancer cell proliferation, induced apoptosis, and boosted the breast cancer cell sensitivity to PTX. Curcumin increases breast cancer cell sensitivity to PTX by inhibiting the secretion of FGF2/FGFR2 from CAFs. Curcumin is a polyphenol isolated from turmeric that belongs to the rhizome of Zingiberaceae. In vivo and in vitro investigations have demonstrated a variety of pharmacological activities of curcumin. In addition to low toxicity, curcumin has pharmacological actions, including anti-inflammation, antioxidation, anti-hyperlipidemia, anti-atherosclerosis, anti-tumor, anti-HIV virus, and other beneficial properties. Many scholars have suggested that curcumin can be utilized to treat malignant tumors and chronic diseases. In vitro and in vivo experiments verified that curcumin has a clear anti-tumor activity. It was reported that curcumin inhibits the development of breast cancer through modulation of multiple molecular targets, including p53, Wnt/β-catenin, and PI3K/Akt/mTOR signaling pathways. Curcumin exhibits diverse pharmacological properties, including anti-inflammation, antioxidant, and anti-tumor. Curcumin exhibits diverse pharmacological properties, including anti-inflammation, antioxidant, and anti-tumor.  Zou et al. focused on the effect of curcumin on the breast cancer cell sensitivity to cisplatin and discovered that curcumin enhanced the cisplatin sensitivity. In addition, curcumin reversed the enhanced resistance in breast cancer cells induced by CAFs-CM. We further detected the roles of FGF2 and its receptor FGFR2 in the chemo-sensitization of curcumin.  Accordingly, curcumin may increase the breast cancer cell sensitivity to PTX by inhibiting the secretion of FGF2 and FGFR2 by CAFs. It provides a new idea for combining curcumin with chemotherapy. This study revealed the potential of curcumin in cancer therapy and provided a foundation for combining curcumin with chemotherapy in the treatment of breast cancer.

The Combination of Vitamin D and Curcumin Piperine Attenuates Disease Activity and Pro-inflammatory Cytokines Levels Insystemic Lupus Erythematosus Patients
Current Rheumatology Reviews | February 2024
Curcumin-piperine might synergise with vitamin D to induce clinical remission in patients with systemic lupus erythematosus. Curcumin supplementation in premenopausal women and dysmenorrhea improves vitamin D levels. Several studies have reported the efficacy of vitamin D or curcumin for SLE treatment. Curcumin is a phenolic compound widely found in ginger, turmeric, and curcuma plants and has the potential as an immunomodulator for the complementary treatment of SLE. Curcumin acts as an activator or inhibitor of several transcription factors that play a role in activating and differentiating Th1, Th2, Th17, and Tregs. In a previous report, curcumin synergistically interacts with vitamin D because it is also a natural ligand for the vitamin D receptor (VDR). Previous studies reveal that administering a combination of curcumin and vitamin D3 resulted in a better recovery of neuronal cells from Alzheimer's disease. Another study demonstrates that curcumin supplementation in premenopausal women and dysmenorrhea improves vitamin D levels. Although vitamin D or curcumin-piperine alone could improve the clinical outcome and cytokines levels in SLE, curcumin-piperine combined with vitamin D had the best outcome in improving the disease activity and cytokines levels among patients.

Can curcumin supplementation break the vicious cycle of inflammation, oxidative stress, and uremia in patients undergoing peritoneal dialysis?
Clinical Nutrition ESPEN | February 2024
Curcumin supplementation for twelve weeks attenuates lipid peroxidation and might reduce uremic toxin in patients with chronic kidney disease undergoing dialysis. Supplementation with 2.5 g of curcumin, three days a week for 12 weeks, reduced the mRNA expression of nuclear factor kappa B (NF-κB) and protein C- high-sensitivity reactive (hs-CRP) in patients undergoing hemodialysis. In this single-blind, randomised, controlled trial, we showed that a 12-week curcumin supplementation reduced the levels of MDA, a standard marker of lipid peroxidation and showed a tendency to reduce the pCS, a uremic toxin from gut microbiota, in patients with chronic kidney disease undergoing dialysis.  A review based on twelve clinical trials comprising 631 patients with chronic kidney disease showed that curcumin supplementation has a favourable impact on oxidative stress, inflammation, and proteinuria. Similarly, a recent study from our group showed that curcumin supplementation for patients with chronic kidney disease CKD undergoing hemodialysis significantly reduced NF-κB mRNA expression and plasma levels of hs-CRP. Curcumin has phenolic groups in its chemical structure, which has essential antioxidant activity as it is a hydrogen donor, stabilising free radical molecules directly. Indeed, curcumin has been tested because of its antioxidant and anti-inflammatory effects in patients with chronic kidney disease CKD. Our results showed that curcumin supplementation may be a potential nutritional strategy to help alleviate oxidative stress.

Effect of curcumin on malignant hepatocytes and mitochondria studied using atomic force microscopy
Micron | February 2024
Curcumin, an active ingredient of Curcuma longa, exerts anti-inflammatory, antioxidant and anticancer effects on the liver (Reyes-Gordillo et al., 2017). Most studies on the effects of curcumin on hepatoma cells have focused on biological processes, including cell apoptosis, gene expression, and the role of proteins (Darvesh et al., 2012). Research has shown that curcumin induces cell apoptosis via the mitochondrial pathway (Trujillo et al., 2014), while research on curcumin in mitochondria has mainly focused on oxidation reactions and protein expressions (Bai et al., 2022). The chemical structure of curcumin is a lipophilicity polyphenol. The viability of SMMC-7721 cells decreased with increasing curcumin concentrations, and the change was statistically significant when the curcumin concentration was higher.

A Review on the Extraction Process and Therapeutic Activity of Curcumin on Diabetes Mellitus and Cancer
International Journal For Multidisciplinary Research | February 2024
Curcumin (diferuloylmethane), the active ingredient in turmeric, has significant antioxidant, anti-inflammatory and anti-cancer properties. Research (in vitro and in vivo) showed that curcumin can also inhibits the activity of some signaling molecules (such as transcription factors, various enzymes, such as protein kinases) and can be modulated in this way inflammatory process, gene expression and could possibly control the effectiveness of curcumin for the treatment of many organ diseases, mainly diabetes and its complications. Turmeric or Curcuma Longa is a natural product whose medicinal properties have been widely studied and a wide range of therapeutic effects in various diseases, including neurodegenerative, liver, kidney damage, cancer and diabetes have been linked mainly to its curcuminoid content. Action of curcumin or curcuminoids as a hypoglycemic agent or only as a healing aid improve metabolic profile and improve diabetes-related complications such as diabetes nephropathy and cardiopathy are discussed. Curcumin has also been shown to be a mediator of chemoresistance and radioresistance. Anticancer effects have been observed in a number of clinical trials, mainly a natural chemopreventive agent in colon and pancreatic cancer, cervical neoplasia and Barrett's metaplasia. The potent antiproliferative effects of curcumin, which interact with multiple intracellular signaling pathways, may enhance the antitumor effects of gemcitabine. Turmeric has also be widely used as antioxidant, antiamyloid, antimicrobial, antitumor, immune response modulating and neuroprotective effects. Curcumin also had antidepressant properties by modulating the release of serotonin and dopamine. Curcumin has been used as a dietary supplement for centuries and is considered pharmacologically safe. The multiple functions of curcumin that affect in a chemopreventive and directly therapeutic way show that it could be a potential anti-cancer drug. Curcumin promotes cell death in a variety of animal and human cell lines, including leukemia, melanoma, and breast, lung, colon, kidney, ovary, and liver carcinomas. Curcumin promotes cell death in a variety of animal and human cell lines, including leukemia, melanoma, and breast, lung, colon, kidney, ovary, and liver carcinomas 

The Use of Curcumin in the Treatment of Colorectal, Breast, Lung, and Prostate Cancers: An In Vivo study Update
JLAR | January 2024
Studies have demonstrated that curcumin can potentially treat various cancers. There is evidence that curcumin has significant anti-cancer properties, including tumor growth inhibition, metastasis inhibitory activity, and angiogenesis. Several studies have demonstrated the versatility and potential of curcumin in treating cancer. Curcumin has considerable cancer treatment potential, based on the in-vivostudies. Curcumin and its derivatives have had bifunctional properties in the past two decades, such as antioxidant and anti-inflammatory effects. The anti-cancer properties of curcumin have been demonstrated in vitro and in vivo at all stages of cancer growth, including the disease's promotion and initiation. Curcumin treats a wide range of diseases, including asthma, allergies, coughs, bronchial hyperactivity, sinusitis, anorexia, coryza, and hepatitis. Many studies show its anti-inflammatory, antioxidant, anti-infectious, hepatoprotective, thrombosuppressive, cardioprotective, chemopreventive, anti-arthritic, and anticarcinogenic properties. Curcumin has also modulated several molecular targets in the body.  According to the combined evidence presented in the included studies, curcumin is potentially effective against various types of cancer, highlighting its numerous anti-cancer properties. Researchers have found that curcumin inhibits tumor growth, induces apoptosis, suppresses angiogenesis, and modulates several cellular signaling pathways against cancer. Considering its broad spectrum of action, curcumin may be used as a complementary treatment and an adjunct therapy for these common types of cancer. As a result of this systematic review, curcumin has the potential to be a promising anti-cancer agent against colorectal, lung, prostate, and breast. It is clear that curcumin has excellent potential as a cancer treatment agent, and further study of its potential is warranted to achieve more effective and holistic cancer treatments.

Protective role of curcumin in disease progression from non-alcoholic fatty liver disease to hepatocellular carcinoma: a meta-analysis
Frontiers in Pharmacology | January 2024
Curcumin demonstrates a significant improvement in key indicators across the stages of NAFLD, liver fibrosis, and HCC. The research results reveal that curcumin effectively hinders disease progression at each stage by suppressing inflammation. Curcumin exerted hepatoprotective effects in the dose range from 100 to 400 mg/kg and treatment duration from 4 to 10 weeks. With excellent anti-inflammatory, antioxidant, and anti-cancer properties, curcumin is expected to be an effective treatment for all stages of liver disease. Based on the results of the quantitative analysis evaluated in this system, we can conclude that curcumin is applicable to a spectrum of NAFLD–LF–HCC models and that most liver diseases proceed based on the hepatic inflammatory microenvironment. More attention should be paid to the anti-inflammatory effects of curcumin.  Curcumin has been shown to be effective in inhibiting the progression of NAFLD–LF–HCC at doses of 100–400 mg/kg over a 4–8 weeks duration with significant hepatoprotective effects, and its therapeutic mechanisms are related to multiple pathways, including anti-inflammatory, antioxidant, and apoptotic regulations which are regulated in all stages of liver disease.

The Effect of Curcumin on the Gut-Brain Axis: Therapeutic Implications
Journal of Neurogastroenterology and Motility | January 2024
Several types of nutrients, such as curcumin, have been proposed as regulators of the dysbiotic state, and preclinical experiments have suggested that curcumin is not only beneficial but also safe. Curcumin possesses anti-inflammatory, anti-atherosclerotic, neuroprotective and metabolic disorder-modulatory effects. Indeed, the gut microbiota directly interacts with curcumin to produce small catabolites that can be absorbed through the intestinal wall, as confirmed by the high concentration of curcumin in the gut after oral administration. In addition, curcumin influences the gut microbiota by promoting the growth of beneficial bacterial strains, improving microbial richness and diversity as well as enhancing intestinal barrier function. Curcumin also had beneficial effects on the gastric tissue of diabetic gastroparesis model rats, exhibiting anti-gastroparetic properties through improving ghrelin (a gut-brain peptide hormone) expression, thereby balancing energy and promoting gastrointestinal motility in the presence of oxidative stress. Likewise, curcumin demonstrated a modulatory role on gastric emptying via enhancing stem cell factor/c-kit signaling (through reduction of oxidative stress) and the nuclear factor kappa B cascade in the stomach of a diabetic gastroparesis rat model.  In fact, curcumin may be one of the non-invasive alternatives to the invasive oral endoscopic gastric myotomy procedure. Curcumin positively affects multiple pathways in Parkinson’s disease (PD) treatment such as the inhibition of α-synuclein aggregation, an increase in tyrosine hydroxylase, and reduction of N-acetylneuraminate degradation, along with its influence on gut microbiota. Some in vivo studies have indicated that the protective effect of curcumin on neurodegenerative diseases and PD occurs through the regulation of the gut microbiota by curcumin. Oral administration of curcumin can alter the diversity of beneficial or pathogenic bacteria accord- ing to the dose, duration of treatment or formulation. In addition, curcumin and its metabolites may have a direct impact on neurons, hormones, blood, lymphatic vessels, and immune cells; thus, it is likely that the direct and indirect effects of curcumin (gut-brain axis) act together synergistically to modulate disease and improve host health. Based on the beneficial effects of curcumin on health-promotion, disease management, and its wide application as a spice in daily food, this review has sought to understand the interplay between curcumin and the gut-brain axis in multiple diseases, mainly based on available in vivo experimental models. The findings presented here indicate that curcumin has promising potential, with acceptable efficacy, as a regulator of the gut-brain axis in several dis- eases associated with GM dysbiosis. In addition, curcumin can not only act as a treatment but is also able to interact with intestinal microflora in dysbiosis to target microbiota activation or suppression, thereby enhancing its therapeutic effect through the production of more active metabolites and better pharmacokinetics.

Curcumin Mitigates the High-Fat High-Sugar Diet-Induced Impairment of Spatial Memory, Hepatic Metabolism, and the Alteration of the Gut Microbiome in Alzheimer’s Disease-Induced (3xTg-AD) Mice
Nutrients | January 2024
Curcumin enriched beneficial gut microbiota. The observed alteration in these gut microbiota profiles suggests a potential crosswalk in the liver and brain for regulating metabolic and cognitive functions, particularly in the context of obesity-associated cognitive disfunction, notably Alzheimer’s disease. Curcumin, a major bioactive chemical constituent derived from turmeric, has been found to exhibit a range of neuroprotective effects, including the reduction in the amyloid burden, neuroinflammation, oxidative stress, infection, and inflammation. Previous findings also provided evidence of the modulatory role of curcumin in mediating several targets of metabolic diseases. Reduced plasma glucose and triglyceride and improved β cell function and afamin levels were also evident after curcumin consumption in some clinical trials. Our previous studies have demonstrated the protective effects of curcumin on metabolic dysfunctions such as body weight gain, liver fat accumulation, and dysregulated insulin homeostasis in HFHSD-fed middle-aged and old mice. Curcumin supplementation demonstrated a notable impact on body weight gain in the 3xTg-AD mice subjected to HFHSD. This aligned with the previous findings from our studies and others, revealing a consistent reduction in body weight in the mice following curcumin supplementation, particularly under various metabolic challenges. Curcumin supplementation effectively ameliorated these memory deficits, as evidenced by an enhanced performance during the Y-maze test, consistent with our prior finding. In conclusion, our study demonstrated the multifaceted effects of curcumin on the body weight, metabolic pathways, memory function, and gut microbiota in 3xTg-AD mice under HFHSD conditions. The selective reduction in body weight gain, improvements in memory function, and the modulation of the metabolic pathways suggest the potential therapeutic value of curcumin in mitigating Alzheimer’s-related symptoms.

Curcumin Inhibits Bladder Cancer by Inhibiting Invasion via AKT/MMP14 Pathway
Discovery Medicine | January 2024
Curcumin could inhibit bladder cancer by inhibiting invasion through the AKT/MMP14 pathway. The target of curcumin for bladder cancer includes signal transducer and activator of transcription 3 (STAT3), AKT, cyclin A2 (CCNA2), epidermal growth factor receptor (EGFR), E1A binding protein p300 (EP300) and MMP14. MMP14 was highly expressed in bladder cancer than in normal tissues and was associated with a worse prognosis (p < 0.05). Curcumin could inhibit the proliferation and migration of bladder cancer cells.

Targeting endothelial cells with golden spice curcumin: A promising therapy for cardiometabolic multimorbidity
Pharmacological Research | January 2024
Curcumin, a widely used dietary supplement derived from the golden spice Curcuma longa, has demonstrated remarkable potential in treatment of CMM through its interaction with endothelial cells. Numerous studies have identified various molecular targets of curcumin (such as NF-κB/PI3K/AKT, MAPK/NF-κB/IL-1β, HO-1, NOs, VEGF, ICAM-1 and ROS). These findings highlight the efficacy of curcumin as a therapeutic agent against cardiometabolic multimorbidity through the regulation of endothelial function. Curcumin, derived from the golden spice Carcuma longa and widely used as a dietary supplement, possesses anti-inflammatory, analgesic, anti-angiogenic and anti-oxidative properties. Several studies have demonstrated that the therapeutic effects of curcumin against cardiometabolic multimorbidity were attributed to its ability to target ECs. Studies have shown that in patients with obesity, curcumin (oral, 1 g/d for 4 weeks) could effectively regulate inflammation and immunity by reducing levels of hs-CRP, IL-1β, IL-4, or VEGF, and decreased levels of MCP-1, IL-6, and TNF-α in serum of metabolic syndrome (MS) patients. Curcumin, a natural compound derived primarily from, the rhizomes of Curcuma longa, possesses significant pharmacological properties. Extensive studies have confirmed its high oral safety. Additionally, our review has highlighted the tremendous potential of curcumin in the treatments a majority of cardiometabolic multimorbidities by the alleviation of endothelial damages. Furthermore, research studies have demonstrated the potential of curcumin in alleviating endothelial inflammation, oxidative stress, and cellular inflammation caused by diverse pathological conditions, such as hyperglycemia, hyperlipidemia, hypertension, atherosclerosis, cerebral ischemia, and myocardial infarction. In animal models of obesity, MS, diabetes, and related complications, curcumin was administered at a higher dose and for a longer duration of 300–400 mg/kg/day for 8–12 weeks. This dosage exceeds the amount used to treat hypertension, atherosclerosis, and cerebral ischemia, which falls within a dosing range of 100–200 mg/kg/day for 4–6 weeks.

Examination of the effect of curcumin supplementation on liver enzymes and some physiological parameters in volleyball players
Revista de Gestão e Secretariado | January 2024
It has been observed that curcumin supplementation applied in addition to volleyball training affects the lipid metabolism and physiological parameters of the athletes. In line with this information, we believe that the supplements to be applied in addition to their routine training will positively affect the athletic performance of the athletes. Curcumin has been investigated for its anti-obesity, anti-inflammation, anti-cancer, anti-angiogenesis, anti-diabetes, hepatoprotection, radioprotection, and chemopreventive action. Curcumin is also said to affect obesity and lipid metabolism via a number of pathways, including energy metabolism regulation, inflammation suppression, and angiogenesis. Turmeric has lately gained widespread interest from researchers who have done studies demonstrating that its therapeutic characteristics are linked to pain relief, as well as the prevention and treatment of cardiovascular, cancer, and other chronic diseases. Curcumin administration has also been shown to improve physical activity and sports performance in animal studies. Curcumin supplementation is said to aid in muscle repair and  inflammation reduction, improve mitochondrial biogenesis, reduce oxidative stress, and prevent fatigue and muscle damage. During aerobic exercise (1 hour treadmill jog), there was a substantial reduction in physical exercise-derived inflammation compared to the pre-exercise moment in studies when turmeric supplementation was used. Despite some inconsistent results, curcumin administration appears to be useful for pain relief as well as muscle damage mitigation by lowering serum CK. Nicol et al. (2015) found that those treated with curcumin (5 g/day -5 days) had less muscular pain and lower CK serum values (22-9%; ± 21-22%) at 24-and 48 hours. Curcumin supplementation for 8 weeks resulted in substantial improvements in CRP, LDH, MDA, and VO2 max values in healthy young adult women in trials. It has been observed that curcumin supplementation applied in addition to volleyball training affects the lipid metabolism and physiological parameters of the athletes. In line with this information, the diversity of nutrients or compounds derived from food factors or medicinal plants can be explored to understand their possible effects on exercise physiology and the different bioactivities that can be used for health promotion.

Profiling Inflammatory Biomarkers following Curcumin Supplementation: An Umbrella Meta-Analysis of Randomized Clinical Trials
Evidence-Based Complementary and Alternative Medicine | January 2024
The umbrella of meta-analysis suggests curcumin as a promising agent in reducing inflammation as an adjunctive therapeutic approach in diseases whose pathogenesis is related to a higher level of inflammatory biomarkers. Curcumin is remarkable bioactive polyphenol extracted from the rhizome of turmeric (Curcuma longa). Curcumin has a wide range of medicinal effects such as hepatoprotective, antimicrobial, anti-inflammatory, antioxidant, and antitumor activities. The anti-inflammatory feature of curcumin is mediated by several pathways. Intestinal alkaline phosphatase, an endogenous antioxidant and anti-inflammatory enzyme, is upregulated by curcumin. Moreover, curcumin modulates inflammatory markers through nuclear factor-erythroid factor 2-related factor 2 (NRF2∗)-Keap1 regulatory pathway. Given these effects, curcumin can have regulatory effects on the level of inflammatory biomarkers such as CRP, IL-6, and TNF-α. According to the US Food and Drug Administration (FDA) report, curcumin has been considered as “Generally Recognized as Safe” (GRAS) even at doses between 4000 and 8000 mg/day. The beneficial effect of curcumin on various health conditions in some studies shows that the anti-inflammatory effect of curcumin is not dependent on the disease. Curcumin has a polyphenol nature; therefore, its anti-inflammatory mechanisms may be due to its antioxidant properties. Many properties of curcumin such as antioxidant, anti-inflammatory, antimicrobial, and antimutagenic attribute to the presence of hydroxyl and methoxy groups in the curcumin structure. The present study shows that curcumin has reducing effects on IL-6, CRP, and TNF-α levels. Therefore, curcumin can be considered as a useful agent for longevity through decreasing oxidative stress.

Anti-Inflammatory Mechanisms of Curcumin and Its Metabolites in White Adipose Tissue and Cultured Adipocytes
Nutrients | January 2024
Overall, our in vivo and in vitro studies demonstrate that curcumin alleviated diet-induced obesity-associated inflammation. The plant-derived polyphenol curcumin alleviates the inflammatory and metabolic effects of obesity, in part, by reducing adipose tissue inflammation. Both curcumin and its metabolites reduced LPS-induced adipocyte IL-6 secretion and mRNA levels. Proteomic analyses indicated that curcumin upregulated EIF2 and mTOR signaling pathways. Overall, curcumin exerted anti-inflammatory effects in adipocytes. Previously, we reported that curcumin exerted protective metabolic effects in diet-induced obese mice, independent of changes in body weight. Curcumin’s effects may have been mediated through its metabolic products, which are produced in the gut, liver, or other tissues.

The Effects of Curcumin on Neurodegenerative Diseases: a Systematic Review
Journal of Herbal Medicine | January 2024
Curcumin has been considered in the therapeutic approach to neurodegenerative diseases due to its relevant antioxidant and anti-inflammatory properties. Adding curcumin to traditional drug therapy appears promising and safe for treating neurodegenerative diseases. Curcumin could be an option due to its antioxidant, anti-inflammatory, and immunomodulatory properties (Colaço et al., 2023, Grant et al., 2023, Marton et al., 2022). The consumption of this plant or its derivatives, such as curcumin, can improve the function and structure of synapses by regulating proteins and delaying neuronal dysfunction processes.

Antioxidant curcumin induces oxidative stress to kill tumor cells (Review)
Oncology Letters | January 2024
Curcumin is a plant polyphenol in turmeric root and a potent antioxidant. Curcumin is a plant polyphenol in the rhizome of turmeric and was classified as a third-generation cancer chemopreventive agent by the National Cancer Institute. Several studies have reported anticancer mechanisms mediated by curcumin through the induction of elevated ROS. Curcumin has anti-inflammatory, antibacterial, hepatoprotective and anticancer properties, and its anticancer effects have been reported in several tumor types. In melanoma, curcumin has been reported to increase the ROS level and activate oxidative stress in the cysteine asparaginase pathway, which causes tumor cell death. Furthermore, curcumin-induced accumulation of ROS in tumors to kill tumor cells has been noted in several studies, as discussed in the present review. Curcumin is well tolerated by humans. For example, a study that evaluated the toxicity of curcumin in humans reported that subjects administered 8 mg/day curcumin did not develop toxicity. Curcumin is a natural compound that has been used for the treatment of numerous types of diseases, such as Alzheimer's disease, fatty liver and cancer. Of note, curcumin has a dual role in oncological and non-oncologic diseases. Specifically, in non-neoplastic diseases, curcumin is a potent antioxidant that attenuates oxidative stress and mitochondrial damage. Conversely, in tumors, curcumin binds to several enzymes and increases ROS levels. These different effects may be the result of differences in dosage. For instance, in a previous study on curcumin treatment of drug-resistant tumor cells, a low dose of curcumin showed no effect on antioxidant proteins, whereas a high dose resulted in the inhibition of antioxidant proteins, thereby increasing ROS levels. Furthermore, mitochondria may be a potential target for high-dose curcumin. In addition, compared with normal cells, proteins abnormally expressed in tumor cells, such as GSH and HO-1, may be targeted by curcumin to cause oxidative stress in tumor cells.  In terms of autophagy, curcumin has been reported to induce elevated ROS levels and the appearance of autophagy markers and autophagosomes, causing tumor cells to undergo autophagy. Curcumin achieves anticancer effects by regulating the expression of Nrf2 and its downstream target HO-1, inhibiting the expression of GPX4 and altering the accumulation of intracellular iron and inducing the Fenton reaction. Over the past two decades, the mechanisms by which curcumin inhibits several types of tumor have been gradually elucidated.  In conclusion, curcumin may have the potential to become a cutting-edge drug for the treatment of tumors and other diseases.

Antioxidant, anti-inflammatory and epigenetic potential of curcumin in Alzheimer's disease
BioFactors | January 2024
Curcumin - an integral component of traditional medicine in numerous cultures worldwide - has garnered interest as a promising Alzheimer's disease treatment. Current research indicates that curcumin may exhibit therapeutic potential in neurodegenerative pathologies, attributed to its potent anti-inflammatory and antioxidant properties. Additionally, curcumin and its derivatives have demonstrated an ability to modulate cellular pathways via epigenetic mechanisms. This article aims to raise awareness of the neuroprotective properties of curcuminoids that could provide therapeutic benefits in Alzheimer's disease. The paper provides a comprehensive overview of the neuroprotective efficacy of curcumin against signaling pathways that could be involved in Alzheimer's disease and summarizes recent evidence of the biological efficiency of curcumin in vivo. Curcumin is a naturally occurring polyphenol found in turmeric, which has long been utilized in traditional medicine for its anti-inflammatory and antioxidant properties. Curcumin's anti-inflammatory properties stem from its capability to inhibit multiple proinflammatory signaling pathways mediated by nuclear factor kappa B (NF-kB) and immune cell activation. Through this modulation of inflammatory mediators, encompassing cytokines, adhesion molecules, growth factors, and enzymes, curcumin holds the potential for therapeutic benefits. Numerous studies have investigated the therapeutic potential of curcumin against various neurodegenerative diseases, including Alzheimer's disease. Some evidence suggests that curcumin may be able to counteract the formation of amyloid plaques. Additionally, curcumin has been found to modulate Alzheimer's disease-associated epigenetic changes by influencing methylation patterns, microRNAs, and histone-modifying enzymes. Multiple human studies suggest a potential of curcumin to modulate Alzheimer's disease pathways in-vivo. Zhang et al.'s 2006 findings demonstrated in-vivo effectiveness of curcumin in clearing amyloid deposits. It was observed that treatment of macrophages of Alzheimer's disease patients with curcuminoids notably enhanced the uptake of Aβ. Research by DiSilvestro et al. extended these findings, investigating the effect of curcumin on inflammatory pathways and Aβ clearance in healthy middle-aged individuals. Daily administration of a low dose of curcumin has exhibited potential in reducing plasma levels of Aβ protein and augmenting antioxidant capacity by elevating the levels of radical scavenging enzymes catalase and myeloperoxidase. In a different study, a solid lipid formulation of curcumin was observed to enhance cognitive performance, alleviate fatigue, and mitigate the detrimental effects of psychological stress. Further exploration into the therapeutic potential of curcumin in Alzheimer's disease was initiated by Baum et al.'s double-blind study in 2008. Their 6-month clinical study confirmed the previously described advantageous effects of curcumin in Alzheimer's disease, as such showing its potential to promote disaggregation of Aβ and anti-inflammatory and antioxidant responses. In 2020, Thota et al. demonstrated that daily oral curcumin supplementation for 12 weeks could decrease circulating levels of islet amyloid peptide (IAPP) and glycogen synthase kinase-3 (GSK-3β), both implicated in insulin resistance. Curcumin and its metabolites have been shown to play a neuroprotective role, with the capacity to alter the pathological sequelae that may lead to Alzheimer's disease. Curcumin's demonstrated antioxidant and anti-inflammatory role, along with its high safety profile, poses an intriguing possibility in preventing and treating Alzheimer's disease.

Curcumin in Alzheimer’s Disease and Depression: Therapeutic Potential and Mechanisms of Action
Brazilian Archives of Biology and Technology | January 2024
Curcumin is a polyphenol present in Curcuma longa, a root used in Asian cuisine for thousands of years, and it has several medicinal properties, acting as an antioxidant, anti-inflammatory, anticancer, among others. The data analyzed demonstrated that curcumin supplementation is able to restore BDNF (Brain Derived Neurotrophic Factor) levels in Alzheimer's disease and depression, in addition to modulating monoamines and reducing oxidative stress, inflammation, beta-amyloid aggregation, Tau protein accumulation and aluminum neurotoxicity, improving their symptoms. Curcumin has several medicinal properties as antioxidant, anti-inflammatory, anti-HIV, antibacterial and antitumor effect. In addition, curcumin is also used as a therapeutic agent in inflammatory bowel disease, pancreatitis, arthritis, some types of cancer [24], head trauma, anxiety, Parkinson’s, depression, Alzheimer's disease, as well as acting as BDNF restorer. Most of curcumin benefits can be attributed to its anti-inflammatory action, obtained by the modulation of the expression and production of enzymes such as cyclooxygenase-2 (COX-2), lipoxygenase and inducible nitric oxide synthase (iNOS), and by the inhibition of inflammatory cytokines, including interleukin and tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein (MCP), among others. In neurodegenerative and neuropsychological diseases, curcumin's  role in restoring BDNF levels and, consequently, promoting neurogenesis, is extremely important and may contribute to the reversal of cognitive and mood disorders. After chronic curcumin supplementation, subjects had a significant reduction in depressive symptoms, with a reduction in the Hamilton Depression scale and the Montgomery-Asberg scale. Curcumin supplementation was also able to elevate plasma BDNF levels and reduce inflammatory cytokines TNF-α and IL-1β, and salivary cortisol concentrations, when compared to the placebo group. These results suggest that supplementation with curcumin is able to improve the action of selective serotonin reuptake inhibitor class of antidepressants, such as escitalopram, mainly by increasing BDNF levels, inhibiting proinflammatory cytokines and reducing cortisol secretion. Therefore, there is strong evidence of curcumin potential as a therapeutic agent in the neuropsychological and neurodegenerative context, especially when used in more bioavailable and high-quality formulations. In summary, the data presented suggests that curcumin is able to prevent and improve the symptoms of Alzheimer’s disease through the improvement of cognitive and memory deficit by restoring BDNF levels, reducing oxidative stress, inflammation, beta-amyloid aggregation, Tau protein accumulation and aluminum neurotoxicity. In Depression, curcumin treatment was also able to improve its symptoms by restoring BDNF levels, modulating monoamines and reducing inflammation. This study helps to clarify the various mechanisms of action of curcumin in the neurodegenerative / neuropsychological diseases, Alzheimer’s disease and depression, suggesting it as a potential therapeutic agent without any significant side effects.

Targeted therapies of curcumin focus on its therapeutic benefits in cancers and human health: Molecular signaling pathway-based approaches and future perspectives
Biomedicine & Pharmacotherapy | January 2024
Curcumin modulates several biochemical pathways and targets involved in cancer growth. Owing to its anti-inflammatory, antioxidant, mutagenic, and antibacterial properties, curcumin has been utilized as medication in Asian countries owing to their antioxidant and anticancer activities.  Additionally, it has been shown to be advantageous for kidneys. Curcumin has several medical uses, most of which are attributed to its inflammatory and antioxidant properties. Curcumin has anticancer, anti-inflammatory, antioxidant, and neuroprotective properties, potentially managing diabetes, easing arthritis, and potentially reducing inflammation in bowel diseases. Curcumin can cure metabolic syndrome, anxiety, hyperlipidemia, and oxidative and inflammatory diseases. Furthermore, a low dose can still be beneficial for one's health, even if they have not been diagnosed with a health condition. It has great potential as a cancer treatment.

Curcumin and breast cancer: therapeutic potential and mechanism in multi-drug resistance
Cancer Genomics | January 2024
The sensitizing effects of curcumin have been studied in composition with chemotherapy drugs including cisplatin,paclitaxel, doxorubicin, and 5-fluorouracil in BC celllines such as MCF-7, MCF-7ADR, MDA-MB-231. Studies reported that curcumin increases the sensitivity in the resistant cells to chemotherapy drugs, which has apoptotic and growth inhibitory effects. Also, curcumin could decrease multi-drug resistance breast cancer through induction ofautophagy by down-regulate the expression of CCAT1, PI3K/Akt/mTOR pathway.  According to the results of preclinical studies, curcumin administration can inhibit the multi-drug resistance in breast cancer cells.

Analysis: Aaron Rodgers' remarkable recovery sets standard for players who tear an Achilles tendon
The Independent | January 2024
Aaron Rodgers defied conventional medicine by returning to practice just 77 days after surgery for a torn Achilles tendon. Rodgers had a “speed bridge” procedure that’s designed to expedite the recovery process. He said Thursday that he attributes his progress to working hard in rehab and a strict diet: “High levels of curcumin, high levels of collagen and drinking freakin’ bone broth every single day.” The soon-to-be 40-year-old Rodgers may have cracked the code for an injury that’s typically season-ending and normally takes players at least nine months to recover. No professional athlete is known to have returned from it in less than five months.

Curcumin for Treating Breast Cancer: A Review
Pharmaceutics | January 2024
Curcumin, a phytochemical derived from Curcuma longa (turmeric), has shown substantial potential in inhibiting BC cell migration, metastasis, and proliferation. Curcumin constitutes the primary bioactive compound found in the plant Curcuma longa, commonly known as turmeric. Curcumin, a natural compound found in the turmeric plant Curcuma longa, is generally considered safe when consumed in amounts commonly found in foods and traditional herbal remedies. In 2021, the European Food Safety Authority (EFSA) established an acceptable daily intake of curcumin at 3 mg/kg body weight. For optimal pharmacological effects, an oral dose of more than 8.0 g/day is often required. Numerous clinical studies demonstrated that a daily intake of 12 g of curcumin is well tolerated and safe. Curcumin unquestionably exhibits potential as an anticancer agent, with relevance not only to breast cancer but also to lung cancer, gastric cancer, and other malignancies.

Protective role of curcumin in disease progression from non-alcoholic fatty liver disease to hepatocellular carcinoma: a meta-analysis
Frontiers in Pharmacology | January 2024
Curcumin demonstrates a significant improvement in key indicators across the stages of NAFLD (Non-Alcoholic Fatty Liver Disease), liver fibrosis, and HCC (Hepatocellular Carcinoma). The research results reveal that curcumin effectively hinders disease progression at each stage by suppressing inflammation. With excellent anti-inflammatory, antioxidant, and anti-cancer properties, curcumin is expected to be an effective treatment for all stages of liver disease. This is the first meta-analysis to correlate Non-Alcoholic Fatty Liver Disease, liver fibrosis, and hepatocellular carcinoma and evaluate the therapeutic effects of curcumin on systemic liver disease. The mechanisms of curcumin in the inhibition of the transition from Non-Alcoholic Fatty Liver Diseaseto HCC are multiple, well-established, and multi-targeted. The phenotypes involved are mainly related to oxidative stress, inflammation, and apoptosis. Based on the results of the quantitative analysis evaluated in this system, we can conclude that curcumin is applicable to a spectrum of Non-Alcoholic Fatty Liver Disease–LF–HCC models and that most liver diseases proceed based on the hepatic inflammatory microenvironment. In the development of a range of liver diseases, one of the most remarkable molecular changes driving the Non-Alcoholic Fatty Liver Disease–LF–HCC axis is the NF-κB signaling pathway, so anti-inflammatory processes play a crucial role in all three disease stages. More attention should be paid to the anti-inflammatory effects of curcumin. Curcumin exerted hepatoprotective effects in the dose range from 100 to 400 mg/Kg and treatment duration from 4 to 10 weeks. The mechanistic analysis reveals that curcumin primarily exerts its hepatoprotective effects by modulating multiple signaling pathways, including TLR4/NF-κB, Keap1/Nrf2, Bax/Bcl-2/Caspase 3, and TGF-β/Smad3. In summary, curcumin has shown promising therapeutic effects during the overall progression of Non-Alcoholic Fatty Liver Disease-LF-HCC. It inhibited the pathological progression by synergistic mechanisms related to multiple pathways including anti-inflammatory, antioxidant, and apoptosis regulation.

Therapeutic effects of curcumin on constipation-predominant irritable bowel syndrome is associated with modulating gut microbiota and neurotransmitter
Frontiers in Microbiology | January 2024
In a 30-day randomized trial, in subjects with irritable bowel syndrome, abdominal bloating can be successfully reduced with a supplementation with curcumin (Giacosa et al., 2022). Previous studies have shown that CUR has a significant effect on reducing the levels of 5-HT in serum and colon (Yu et al., 2019). Curcumin  is the major active constituent of Curcuma longa. Modern studies have demonstrated its potent anti-inflammatory (Kocaadam and Şanlier, 2017), antioxidant (Ahangarpour et al., 2019), and antidepressant (Chang et al., 2016) effects. It has been found that treatment with curcumin can modulate 5-HT levels, with treatment with curcumin significantly increasing 5-HT levels in the hippocampus, while decreasing 5-HT levels in the colon in IBS models (Yu et al., 2015). Curcumin can interact directly with the gut microbiota. Curcumin has been shown to positively affect the gut microbiota and modulate microbiota composition and function, further improving gut health (Ng et al., 2018). These studies support the potential therapeutic effect of curcumin on IBS-C through modulation of the gut microbiota and neurotransmitters. The results of this study show that curcumin is able to decrease the levels of HT, VIP and SP and regulate the gut microbiota in rats with irritable bowel syndrome-C, and then exert the therapeutic effect on irritable bowel syndrome-C. The results suggest that curcumin may represent a treatment option for irritable bowel syndrome-C through modulation of the gut microbiota and relevant neurotransmitters. Our results support the possibility of using curcumin to treat irritable bowel syndrome-C patients.

The impact of ginger and curcumin on diabetic nephropathy induced by streptozotocin in rats
European Journal of Translational and Clinical Medicine | January 2024
Curcumin is a potent component in herbal medicine and is extensively studied for various health conditions. Its primary compound, polyphenol curcumin, exhibits powerful anti-inflammatory, antioxidant, and anticarcinogenic properties. In diabetes management, curcumin’s effectiveness lies in its interaction with key molecules and pathways crucial in the disease’s progression. Studies show curcumin’s ability to alleviate insulin resistance, a factor in metabolic syndrome. Both ginger and curcumin contain antioxidants that activate redox-sensitive transcription factors, bolstering cellular antioxidant defenses. Given the importance of dietary management in diabetes, interventions using natural substances like ginger and curcumin offer promising strategies to mitigate the renal complications of DM. Ginger and curcumin extract contained the highest phytochemical content and  anti-oxidant activity (AOA). The high glycoside content was recorded in curcumin. The high terpene content was recorded in curcumin extract. The highly alkaloid content was recorded in curcumin extract. Our results demonstrated the anti-inflammatory and the antioxidant effects of ginger and curcumin extracts, administered individually or in combination. Our data have also shown that ginger and curcumin extracts helped manage STZ-induced diabetic nephropathy and oxidative stress via significant suppression of the NF-κB gene expression. These extracts possess anti-inflammatory potential by suppressing inflammatory cytokines and modulators through the suppression of redox-based NF-κB activation.

Evaluating the potential of Vitamin D and curcumin to alleviate inflammation and mitigate the progression of osteoarthritis
PLoS One | January 2024
This study, for the first time, provides evidence of the mitigating effect of Vitamin D and curcumin on PAR-2 mediated inflammation. Nutraceuticals, such as Vitamin D and curcumin, present potential therapeutic alternatives, offering anti-inflammatory effects, potentially addressing osteoarthritis inflammation. This study presents robust evidence that Vitamin D and curcumin might represent a pioneering, natural, and efficacious therapeutic strategy for managing osteoarthritis and mitigating its related symptoms, specifically those exacerbated by PAR-2 signaling. In conclusion, our study demonstrates that both Vitamin D and curcumin can attenuate the pro-inflammatory response in chondrocytes by inhibiting PAR-2 signaling, reducing the expression of TNF α, IL 6, and IL 8, as well as the RANKL/RANK system. Moreover, these bioceuticals also reduce IFN γ expression, which amplifies the inflammatory events in OA. These findings suggest that Vitamin D and curcumin have potential therapeutic benefits in the management of osteoarthritis.

The impact of ginger and curcumin on diabetic nephropathy induced by streptozotocin in rats
European Journal of Translational and Clinical Medicine | January 2024
Our results demonstrated the anti-inflammatory and the antioxidant effects of ginger and curcumin extracts, administered individually or in combination. Our data have also shown that ginger and curcumin extracts helped manage STZ-induced diabetic nephropathy and oxidative stress via significant suppression of the NF-κB gene expression. These extracts possess anti-inflammatory potential by suppressing inflammatory cytokines and modulators through the suppression of redox-based NF-κB activation. Our findings indicate that ginger and curcumin extracts have therapeutic potential in mitigating functional and structural alterations in the kidneys of diabetic rats, possibly due to their anti-diabetic and anti-inflammatory properties. Rats treated with combined ginger and curcumin extracts had superior outcome in terms of more antioxidant activity, better glycemia management and less DN-related kidney damage (reduced albuminuria and less histological changes). Ginger and curcumin are two well-known functional foods from the Zingiberaceae family that have anti-inflammatory qualities. Curcumin is a potent component in herbal medicine and is extensively studied for various health conditions. Its primary compound, polyphenol curcumin, exhibits powerful anti-inflammatory, antioxidant, and anticarcinogenic properties. In diabetes management, curcumin’s effectiveness lies in its interaction with key molecules and pathways crucial in the disease’s progression. Studies show curcumin’s ability to alleviate insulin resistance, a factor in metabolic syndrome. Both ginger and curcumin contain antioxidants that activate redox-sensitive transcription factors, bolstering cellular antioxidant defenses. Given the importance of dietary management in diabetes, interventions using natural substances like ginger and curcumin offer promising strategies to mitigate the renal complications of diabetes.

Therapeutic Potential of Curcumin, a Bioactive Compound of Turmeric, in Prevention of Diabetes through the Modulation of Oxidative Stress and Inflammation
Molecules | January 2024
In physiological and biochemical studies, it was found that curcumin decreases glucose, creatinine, urea, and inflammatory markers and increases antioxidant enzyme levels. In addition, the histopathological findings revealed that curcumin plays a significant role in the maintenance of renal tissue architecture through the reduction in all pathological changes. This study showed that curcumin has a vital role in the regulation of the expression pattern of the IL-6 protein and fibrosis. Based on biochemical and histopathological findings, this study delivers a scientific suggestion that curcumin could be a suitable remedy in the management of diabetes mellitus. The novelty of the current study is that curcumin showed anti-fibrotic potential by reducing collagen fiber deposition. Curcumin treatment showed a significant decrease in parameters and an increase in insulin level as compared to negative control rats. Oral administration of curcumin significantly ameliorated changes. Hence, based on biochemical and histopathological findings, this study delivers a scientific suggestion that curcumin could be a suitable remedy in the management of diabetes mellitus. Curcumin, a yellow-colored compound, is produced by plants of Curcuma longa species, and it is chemically known as 1,7-bis(4-hydroxy-3-methoxyphenyl)-1, 6-heptadiene-3, 5-dione. It possesses antioxidant, anti-inflammatory, anti-tumor, and other biological activities. Curcumin is capable of exercising its antioxidant action via scavenging a variety of hydrogen peroxide and nitric oxide (NO) radicals and reactive oxygen species (ROS) as superoxide radicals and by preventing lipid peroxidation. Moreover, several in vitro as well as in vivo studies have described that curcumin has potential for treating numerous inflammatory diseases. Curcumin significantly reduced blood urea nitrogen, serum levels of urea, and creatinine and simultaneously reduced albumin/protein urea and increased creatinine clearance. Further, it also prevented damage to renal tubules and the thickness of the basement membrane. Curcumin treatment efficiently counters diabetes-induced oxidative-stress-mediated hepatic damage. Another finding reported that curcumin improved the survival as well as the function of islet cells, with reduced cell apoptosis in the islet of Langerhans and increased insulin secretion in the STZ-induced diabetic model.

Exploring the Potential of Curcumin in Preserving Telomere Length: A New Frontier in Cellular Aging and Health
Medium | January 2024
Curcumin has been valued for centuries for its medicinal properties, particularly its potent antioxidant and anti-inflammatory effects. Recent studies have explored the potential of curcumin in influencing the length and maintenance of telomeres, providing insights into its possible role in combating cellular aging. Curcumin's role in preserving telomere length largely hinges on its antioxidant properties. Oxidative stress, a result of an imbalance between free radicals and antioxidants in the body, is a key factor in the acceleration of telomere shortening. Curcumin, with its strong antioxidant capacity, helps neutralize these free radicals, potentially reducing the rate of telomere shortening and thereby promoting cellular longevity. In addition, the anti-inflammatory properties of curcumin might help mitigate damage, thereby slowing down the rate of telomere attrition. This could be particularly significant in the context of chronic diseases and age-related conditions where inflammation plays a pivotal role. One of the most intriguing aspects of curcumin's relationship with telomeres is its potential effect on the activity of telomerase. Some studies have shown that curcumin might stimulate telomerase activity, thus aiding in the maintenance and even extension of telomere length. This suggests a possible direct intervention in the cellular aging process. The implications of curcumin's effects on telomeres extend to the prevention and management of various diseases. Age-related diseases like cancer, neurodegenerative diseases, and cardiovascular problems have been linked to telomere length. Therefore, by preserving telomere length, curcumin could potentially play a role in mitigating these conditions. Its antioxidant and anti-inflammatory properties, combined with its potential to impact telomerase activity, make it a compound of significant interest in the fields of aging and disease prevention. In the realm of medicine, the exploration of curcumin's role in telomere biology could lead to novel therapeutic strategies. For instance, it could be employed as part of a regimen for diseases where telomere shortening plays a key role.

The effect of curcumin on the necroptosis signaling pathway in colon cancer cells
Bulletin of Biotechnology | January 2024
Curcumin, a yellow compound isolated from the turmeric plant, is important in preventing cancer. Studies have shown that curcumin has an anticancer effect by driving cancer cells into apoptosis, but studies showing its effect on necroptosis are inconclusive. Consequently, the current data clearly suggest that curcumin is a prominent driver of necroptotic signaling-mediated colon cancer cell death. Accumulating mass of indication suggests that curcumin has antioxidant, anti-inflammatory, anti-bacterial, anti-diabetic, and anti-cancer activities (Selvam et al. 2019). Curcumin has shown to have significant impact on many signaling pathways in cancer cells, which controls various cellular activities. The anticancer activities of curcumin have also been shown in colon cancer cells (Selvam et al. 2019). Curcumin has been demonstrated to show anti-cancer activity in HT-19 colon cancer cells by suppressing colony formation, cell viability, and DLEC1 promoter methylation (Guo et al. 2015). In addition, curcumin has been shown to suppress the level of ATG5 (autophagy related 5) protein in HCT-116 cells, leading to the suppression of autophagosome formation, cellular senescence, and cell cycle arrest (Mosieniak et al. Bull Biotechnol (2023). In addition, studies have shown that curcumin has anticancer activity in other colon cancer cells such as Caco-2, HCT-15, and SW620 (Selvam et al. 2019). Curcumin, which is extracted from the plant Curcuma longa, is known to have numerous biological and pharmacological activities. Curcumin has been reported to stimulate cell death pathways such as apoptosis, autophagy, and pyroptosis in many different cancer cells. In a study by Blakemore et al., curcumin was shown to disrupt the cell cycle progression by inducing G2/M cell cycle arrest in various colon cancer cells (Blakemore et al. 2013). In addition, curcumin treatment has been shown to cause abnormal mitotic spindle formation and DNA damage. In addition, curcumin has been shown to dose- dependently suppress cell proliferation. Bull Biotechnol (2023). Remarkably, in our study, curcumin was shown to stimulate necroptosis by increasing the expression of RIPK1, RIPK3, and MLKL genes, especially in HT -29 colon cancer cells. In conclusion, present findings strongly indicates that curcumin is a significant driver of colon cancer cell death mediated by necroptotic signaling.

Curcumin inhibits the invasion and migration of pancreatic cancer cells
European Journal of Nutrition | December 2023
Curcumin is a natural polyphenolic compound with wide-ranging pharmacological effects. Growing evidence suggests that curcumin has anticancer activity against pancreatic cancer, but the mechanism remains incompletely elucidated. Curcumin increased the expression of TFPI-2 mRNA and protein in pancreatic cancer cells and attenuated cell invasion and migration. Curcumin also inhibited ERK and JNK pathways and EMT in pancreatic cancer cells. Knockdown of TFPI-2 partially reversed the inhibition of ERK and JNK pathways and EMT by curcumin. Mechanistically, curcumin upregulated TFPI-2, thereby inhibiting the ERK and JNK pathways, leading to the inhibition of EMT in pancreatic cancer cells. Collectively, curcumin inhibits ERK- and JNK-mediated EMT through upregulating TFPI-2, which in turn suppresses the migration and invasion of pancreatic cancer cells. These findings provide new insights into the antitumor mechanism of curcumin.

Curcumin modulates cell type-specific miRNA networks to induce cytotoxicity in ovarian cancer cells
Life Sciences | December 2023
Curcumin, a natural polyphenolic compound extracted from the rhizomes of the culinary spice turmeric (Curcuma longa), has proven anti-cancer activity against various human cancers and has entered into Phase III clinical trials as monotherapy and in combination therapies for colon (NCT00295035), prostate (NCT03769766, NCT02064673), and pancreatic cancers (NCT00486460). Besides anti-cancer activity, it also exhibits antioxidant, anti-aging, anti-inflammatory, anti-microbial, anti-proliferative, and anti-angiogenic properties. Curcumin exerts such diverse therapeutic properties by interacting and modulating multiple molecular targets, and signaling cascades. Curcumin effectively induces cytotoxicity in many ovarian cancer cell lines and its role as an epigenetic modulator by activating multiple miRNAs in ovarian cancers has been studied. Taken together, in this study, we report a cell-type specific epigenetic role of curcumin, highlighting the distinct miRNAs modulated within the two molecularly distinct ovarian cancer cell lines to render cytotoxicity.

The effects of curcumin-piperine supplementation on inflammatory, oxidative stress and metabolic indices in patients with ischemic stroke in the rehabilitation phase: a randomized controlled trial
Nutrition Journal | December 2023
In the present study, curcumin-piperine supplementation was associated with a significant improvement in physical functioning, role functioning/physical, energy/fatigue, emotional well-being, and social functioning. Moreover, curcumin caused less increase in pain compared with the control group. Curcumin-piperine supplementation had beneficial effects on CIMT, serum hs-CRP, TC, TG, TAC, and systolic and diastolic blood pressure in patients with ischemic stroke in the rehabilitation stage. Curcumin has been shown to serve as a promising factor for preventing stroke and improving its complications in animal studies. Curcumin has many pharmacological activities that are relevant to the treatment of stroke. Preclinical studies have shown the protective effects of curcumin against stroke due to the anti-inflammatory and antioxidant, and anti-ischemic properties of the molecule. Studies showed that apoptosis during ischemia/reperfusion plays an important role in stroke-related brain damage. Curcumin exerts its neuroprotective effect by regulating cell apoptosis and increasing neurogenesis. Animal studies have shown that post-stroke administration of curcumin can significantly reduce lipid peroxidation, mitochondrial dysfunction, glial activation, and infarct volume. In addition, curcumin improves cognitive deficits and motor activity.Despite its high therapeutic potential, curcumin is limited for medical purposes due to its low aqueous solubility, low bioavailability, and rapid degradation. To improve its pharmacokinetic features, co-administration of curcumin with piperine has been introduced as an alternative. Piperine, which is a naturally occurring alkaloid from pepper, has been shown to increase the bioavailability of curcumin and reduce its glucuronidation. It seems that curcumin has several unique properties to improve the health condition of patients with ischemic stroke. The present study showed a decrease in systolic and diastolic | Deblood pressure after 12 weeks of curcumin-piperine supplementation in comparison to placebo. It is suggested that the effect of curcumin on lowering blood pressure is applied through the effect on antioxidant activity and vascular function of this phytochemical. We found that curcumin-piperine intake can lower serum TC and TG concentrations. Other results in this study showed that curcumin-piperine supplementation decreased weight and waist circumference compared with the control group. Results of the current study indicated that curcumin-piperine co-supplementation has beneficial effects on CIMT, systolic and diastolic blood pressure as well as serum levels of hs-CRP, TC, TG, and TAC.

Curcumin/Turmeric Supplementation Could Improve Blood Pressure and Endothelial Function
Clinical Nutrition ESPEN | December 2023
A number of studies have examined the impact of curcumin/turmeric on blood pressure and the factors allegedly responsible for hypertension. In this systematic review and meta-analysis, we tried to sum up the existing literature on randomized controlled trials investigating this hypothesis. Our findings suggested that curcumin/turmeric supplementation significantly improved  systolic blood pressure (SBP), diastolic blood pressure (DBP), blood levels of vascular cell adhesion molecule-1 (VCAM-1), and flow-mediated vasodilation (FMD). Curcumin/turmeric supplementation could be regarded as a complementary method to improve blood pressure and endothelial function.

Antioxidant curcumin induces oxidative stress to kill tumor cells
Oncology Letters | December 2023
Curcumin is a plant polyphenol in turmeric root and a potent antioxidant. It binds to antioxidant response elements for gene regulation by nuclear factor erythroid 2‑related factor 2, thereby suppressing reactive oxygen species (ROS) and exerting anti‑inflammatory, anti‑infective and other pharmacological effects. Of note, curcumin induces oxidative stress in tumors. Curcumin is a plant polyphenol in the rhizome of turmeric and was classified as a third‑generation cancer chemopreventive agent by the National Cancer Institute. Several studies have reported anticancer mechanisms mediated by curcumin through the induction of elevated ROS. Curcumin has anti‑inflammatory, antibacterial, hepatoprotective and anticancer properties, and its anticancer effects have been reported in several tumor types. In melanoma, curcumin has been reported to increase the ROS level and activate oxidative stress in the cysteine asparaginase pathway, which causes tumor cell death. A recent study reported that curcumin downregulated ubiquitin‑specific peptidase 4 to modulate lysosome‑associated membrane protein 3, and thus inhibited the malignant progression of colorectal cancer cells. Furthermore, curcumin‑induced accumulation of ROS in tumors to kill tumor cells has been noted in several studies as discussed in the present review. Curcumin is well tolerated by humans. For example, a study that evaluated the toxicity of curcumin in humans reported that subjects administered 8 mg/day curcumin did not develop toxicity. Curcumin is a natural compound that has been used for the treatment of numerous types of diseases, such as Alzheimer's disease, fatty liver and cancer. Of note, curcumin has a dual role in oncological and non‑oncologic diseases. Specifically, in non‑neoplastic diseases, curcumin is a potent antioxidant that attenuates oxidative stress and mitochondrial damage. In conclusion, curcumin may have the potential to become a cutting‑edge drug for the treatment of tumors and other diseases.

Anti-inflammatory effect of curcumin in an accelerated senescence model of Wistar rat: an in vivo and in-silico study
Journal of Biomolecular Structure and Dynamics | December 2023
Curcumin, a biphenolic substance derived from turmeric (Curcuma longa), offers a number of health-beneficial effects, including anti-inflammatory, cardiovascular protection, anti-cancerous, and anti-angiogenic. Our study provides convincing support for the idea that eating a diet high in curcumin may help to reduce inflammation and help to explain some of its health-beneficial effects.

Curcumin: a bioactive compound with molecular targets for human malignancies
Food and Agricultural Immunology | December 2023
Curcumin has anticancer activity including inducing apoptosis and inhibiting proliferation and invasion of tumours by suppressing a variety of cellular signalling pathways. It also possesses anti-tumour activity on different human cancers such as breast cancer, lung cancer, head and neck squamous cell carcinoma, prostate cancer, and brain tumours. In vitro and in vivo trails, curcumin inhibits tumour development and metastasis by inhibiting many pathways that regulate signalling in malignant cells, including Ras, p53, extracellular signal-regulated kinases (ERK), Wnt-protein kinase B (Akt), MAPKs, and PI3K. Curcumin can also inhibit IKK, EGFR, -catenin, cyclin D1, tumour necrosis factor (TNF), and anti-apoptotic genes such as Bcl-X and Bcl-2 along with downregulating nuclear transcription factors like NF-κB, which reduces the formation of pro-inflammatory cytokines like chemokines, TNF-, Interleukins and IL-1, IL-2, IL-6, IL-8, IL-12.  Curcumin, which comes from the rhizome herb Curcuma longa as well, is renowned as turmeric, it has a polyphenolic composition and it owns a vast range of biological tasks involving antioxidant, anti-inflammatory, hepato-protective, immunomodulatory, anti-depressant, anti-dyslipidemic, antidiabetic, analgesic, and defensive factors against pulmonary diseases. Of specific concern, there have been various studies proposing the effectiveness of curcumin as a chemo protective anti-carcinogenic, and chemo-sensitizing complex besides a variation of cancer forms. The novelty of using curcumin as an anti-cancerous agent lies in its unique ability to target multiple cancer cell signalling pathways by inducing apoptosis, suppressing cell proliferation, inhibiting inflammation and blocking angiogenesis. As evident from the studies, curcumin preferentially kills tumour cells through the control of several cell signalling pathways, according to many in vivo animal studies and in vitro cell cultures. Many studies showed that curcumin's anticancer activity is related to the activation of apoptosis via interference with cell viability signalling pathways. Previous studies have also shown that caspase is involved in curcumin-induced apoptosis. CUR has been shown to trigger caspase-3-independent cell death in human multidrug-resistant cells. Whilst it is not apparent if curcumin can produce ROS or has antioxidant potential, research has shown that curcumin-caused ROS generation and curcumin-induced ROS ultimately result in autophagy activation in cancerous cells. Moreover, curcumin was shown to activate JNK and reduce NF-kB, indicating that these components are implicated in curcumin-induced ROS formation and apoptosis. Findings suggested that curcumin-induced apoptosis is a pro-death signal instead of a pro-survival signal. According to the findings, it was proposed that curcumin induces autophagy in glioma cells to show anticancer activity instead of eliciting a cytoprotective reaction. Since curcumin induces autophagic cell death and can inhibit cell growth, it might be an effective therapeutic drug for cancer therapies. As a polyphenolic, natural substance, it has generated interest as a possible cancer chemotherapeutic agent.

Effects of curcumin on non-alcoholic fatty liver disease: a scientific study
Phytomedicine | November 2023
Curcumin can alleviate insulin resistance, inhibit oxidative stress response, reduce inflammation, reduce liver fat deposition, and effectively improve NAFLD through various modalities, inhibiting the progression into cirrhosis and fibrosis. The review observed that curcumin can activate various signaling pathways such as AMPK and NF-κB to inhibit oxidative stress and apoptosis, thereby reflecting its pharmacological effects: lowering lipid, anti-inflammatory, reducing insulin resistance, and anti-fibrosis. Curcumin also can potentially serve as a primary regulatory target for treating hepatic steatosis using gut microbiota. Curcumin has been found to have a variety of anti-inflammatory, antioxidant, and antitumor effects and affects the lipid metabolism in NAFLD mouse models. In recent years, curcumin has been found to alleviate IR, inhibit the oxidative stress response, reduce inflammation, reduce liver fat deposition, and effectively improve NAFLD through various modalities, blocking the progression into cirrhosis and fibrosis.

Targeting endothelial cells with golden spice curcumin: A promising therapy for cardiometabolic multimorbidity
Pharmacological Research | November 2023
Curcumin shows promise as a potential treatment option for cardiometabolic multimorbidity, particularly due to its ability to target endothelial cells. It represents a novel and natural lead compound that may offer significant therapeutic benefits in the management of cardiometabolic multimorbidity. Curcumin, derived from the golden spice Curcuma longa and widely used as a dietary supplement, possesses anti-inflammatory, analgesic, anti-angiogenic and anti-oxidative properties. Several studies have demonstrated that the therapeutic effects of curcumin against cardiometabolic multimorbidity were attributed to its ability to target ECs. Piperine, for instance, has been found to increase the bioavailability of curcumin significantly. Curcumin, a natural compound derived primarily from, the rhizomes of Curcuma longa, possesses significant pharmacological properties. Notably, as a golden spice, it is widely used in functional foods and dietary supplements. Extensive studies have confirmed its high oral safety, and mature extraction and synthesis methods are available for large-scale production. Additionally, our review has highlighted the tremendous potential of curcumin in the treatments a majority of cardiometabolic multimorbidity by the alleviation of endothelial damages. Furthermore, research studies have demonstrated the potential of curcumin in alleviating endothelial inflammation, oxidative stress, and cellular inflammation caused by diverse pathological conditions, such as hyperglycemia, hyperlipidemia, hypertension, atherosclerosis, cerebral ischemia, and myocardial infarction. Our literature review highlights that the pharmacological effects of curcumin pertain to multiple critical signaling pathways such as NF-κB/PI3K/AKT, MAPK/NF-κB/IL-1β, and ROS-ERK1/2. Its effects are also associated with the modulation of HO-1, MDA, NOs, VEGF, ICAM-1 and ROS levels.

Curcumin and analogues in mitigating liver injury and disease consequences: from molecular mechanisms to clinical perspectives
Phytomedicine | November 2023
Curcumin demonstrates significant therapeutic potential across various medical conditions, particularly emerging as a promising candidate for liver injury treatment. Curcumin boasts remarkable antioxidant properties by neutralizing free radicals and modulating oxidative stress. Curcumin and its analogs have demonstrated low toxicity in vitro and in vivo. Curcumin plays a role in alleviating liver injury by modulating the antioxidant system, as well as cellular and molecular pathways. Curcumin, belonging to the polyphenol class, is a bioactive compound of turmeric (Curcuma longa). It is recognized as a dietary chemoprotective compound, and has properties such as preventing oxidative damage, reducing inflammation, neuroprotection, nephroprotection, hepatoprotection, anti-proliferation, and anti-metastatic effects (Nabavi et al., 2014; Zhao et al., 2023). These functional characteristics endorse its potential as an alternative solution for treating liver injury. Pooled randomized controlled trials indicate that curcumin might have a positive impact on fatty liver by enhancing metabolic indicators and anthropometric measurements (Baziar and Parohan, 2020; White and Lee, 2019). Curcumin and its extracts have the potential to be modified into various analogs. Curcumin emerges as a promising phytomedicine for liver injury owing to its effectiveness in hepatoprotection and low toxicity profile. Curcumin is essential for controlling the liver microenvironment by impacting the complex processes related to the production.The antioxidant, anti-inflammatory, and hepatoprotective properties of curcumin and similar compounds have been acknowledged, making them potential therapeutic agents (Ahmad et al., 2019; Alhusaini et al., 2018; Zhou et al., 2007). They effectively prevent and mitigate liver injury through mechanisms that target tissue cells, metabolic pathways, and the extracellular matrix.

Anti-cancer and Anti-angiogenic Effects of Curcumin and Epigallocathechin-3-Gallate in a Mouse Model of Renal Cancer
 Medicine and Pharmacology, Oncology and Oncogenics | November 2023
Results have shown that curcumin, a component of turmeric (Curcuma longa), and epigallocatechin-3-gallate (EGCG), found in Camelia sinensis, are able to synergistically inhibit cell survival, proliferation and angiogenesis of several types of cancer, including renal carcinoma, as shown in our results, by modulating different signaling pathways. Furthermore, pretreatment of mice with a diet containing 0.6% curcumin prior to ccRCC injection showed significant inhibition of tumor engraftment in 60%. Taken together, our data indicate, for the first time, that the combination of curcumin and EGCG acts in a synergistic manner to inhibit the growth and angiogenesis of ccRCC and with less toxicity than sunitinib and provide an important rationale for future clinical development for chemoprevention and treatment of renal cancer. With our results, we can strongly support the hypothesis that the combination of curcumin and EGCG acts in a synergistic manner to inhibit the growth and angiogenesis of ccRCC, suggesting a possible implication for new therapeutic strategies for the treatment of patients with ccRCC. In this work we demonstrate antiproliferative, antiangiogenic and synergistic effects of some natural compounds as Curcumin and EGCG major active ingredient of green tea for the care of renal cancer. The combination of curcumin and EGCG may produce a better antitumor effect as showed in our data. In summary, our results indicate that the combination of EGCG plus Curcumin show the same effects of tumor growth delay and angiogenesis reduction in an initial phase compared to Sunitinib treated mice. Interestingly, however natural compounds show a longer lasting effect. The antitumoral, antiangiogenic and drug sensibility of the combination of curcumin  and EGCG, encourage their wider use in cancer therapy confirming their synergism of action and low toxicity. Interestingly, these natural compounds can be easily taken orally by the population without any side effects, and this is an important advantage in terms of cancer prevention.

The chemotherapeutic potential and epigenetic regulation of curcumin in lung cancer: a mini review
Naunyn-Schmiedeberg's Archives of Pharmacology | November 2023
In-depth research has been done on curcumin as a multi-target anti-tumor and anti-inflammatory molecule. A pharmacologically active polyphenol produced from turmeric is called curcumin. Over the past few decades, curcumin’s therapeutic potential has been thoroughly studied, and data indicate that curcumin may play a part in a variety of biological processes, most notably its potent anticancer activity. Being a pleiotropic chemical, curcumin regulates a variety of molecules that are key players in many cell signaling pathways. It has been shown to stifle transformation, restrain proliferation, and trigger apoptosis. Curcumin can reduce the development of non-small cell LC by downregulating Circular RNA hsa_circ_0007580, which in turn controls the expression of integrin subunit beta 1 by adsorbing miR-384.

Curcumin alleviates Alzheimer’s disease by inhibiting inflammatory response, oxidative stress and activating the AMPK pathway
Journal of Chemical Neuroanatomy | November 2023
Curcumin not only improved cognitive function and spatial memory, but also alleviated the pathological damage and apoptosis of brain tissues for Alzheimer’s disease mice. Meanwhile, upon curcumin treatment, the number of damaged neurons in Alzheimer’s disease mice was decreased, the level of Aβ1-42 in Alzheimer’s disease mice was significantly decreased. Furthermore, the Alzheimer’s disease mice treated with curcumin exhibited lower TNF-a, IL-6, IL-1β and MDA levels and a higher SOD content. Besides, curcumin also downregulated p65 expression and upregulated AMPK phosphorylation. Curcumin (Cur) is one of the main active ingredients of turmeric (Kim et al., 2019). Curcumin exhibits many pharmacological effects, such as anti-inflammatory (Lee et al., 2020), anti-oxidation (Theppawong et al., 2019) and neuroprotective actions (Rasouli and Ghavami, 2020). Curcumin has been reported to attenuate spatial memory impairment in Wistar rats by exerting anti-inflammatory, anti-apoptosis, and anti-oxidative properties (Hadizadeh-Bazaz et al., 2021). In addition, curcumin can protect the hippocampus from ischemic insult by suppressing the activation of inflammasome via the modulation of AMPK (Li et al., 2015). Curcumin has been used for the treatment of many diseases, particularly those associated with inflammation and oxidative stress (Mohammad Pour et al., 2019, Alizadeh and Kheirouri, 2019). For example, curcumin and its analog have been reported to attenuate inflammation and oxidative stress in the brain tissues of the diabetes mellitus rat models (Miao et al., 2021). Furthermore, Chen et al. have provided substantial evidence that curcumin exerts its neuroprotective effects in animal models of traumatic brain injury by inhibiting the inflammatory response and oxidative stress (Chen et al., 2023). Consistent with previous studies, in this study, we observed that treatment with curcumin not only reduced the levels of inflammatory factors in the serum and hippocampus, but also decreased oxidative stress. In conclusion, this study has revealed the effect and mechanism of curcumin in Alzheimer’s disease, and verified our hypothesis that curcumin may impede the development of Alzheimer’s disease by inhibiting inflammatory response, oxidative stress and activating the AMPK pathway. Curcumin improved learning and memory abilities in Alzheimer’s disease mice. Curcumin ameliorated the spatial working memory in Alzheimer’s disease mice. Curcumin alleviated the pathological damage of brain tissues in Alzheimer’s disease mice. Curcumin enhanced the number of damaged neurons in Alzheimer’s disease mice. Curcumin suppressed the apoptosis of brain tissues in Alzheimer’s disease mice. Curcumin reduced Aβ1-42 deposition in Alzheimer’s disease mice. Curcumin inhibited inflammatory response and oxidative stress in Alzheimer’s disease mice. Curcumin exerted a protective effect on Alzheimer’s disease mice via activation of the AMPK pathway. The findings of the study shed some new light on the treatment of Alzheimer’s disease and the application of curcumin.

Oxidative Stress and Cancer: Harnessing the Therapeutic Potential of Curcumin and Analogues Against Cancer
European Journal of Biology | November 2023
The phytochemical Curcumin has gained ground as an interesting cancer therapeutic. Curcumin is an active phenolic compound used in traditional medicine around the world.  Curcumin is involved in a plethora of clinical trials touching on a wide range of cancers. Taking advantage of curcumin’s innate antioxidant and anti-cancer abilities clinical trials are observing improvements in recurrence-free survival in pancreatic cancer, safety and tolerability in metastatic treatment-resistant colorectal cancer, tumor-induced inflammation reduction in endometrial carcinoma, and efficacy and bioavailability in glioblastoma.  Curcumin has a history of use in medicines in Asian countries where it was used as an anti-inflammatory and anti-dysenteric, and has recently shown antioxidant properties in the context of various disease instances. Curcumin has become a popular drug for cancer therapy over the last few decades and multiple analogs have arisen based on curcumin structure. Mechanistically, curcumin has shown the ability to regulate a plethora of molecular targets lending to its anti-cancer properties. The transcription factor NF-kB is one of the longest known targets of curcumin and its suppression in a variety of cancers including leukemia and melanoma. Natural compounds like curcumin are especially advantageous in this aspect due to their low toxicity towards healthy cells.

Curcumin Disrupts a Positive Feedback Loop between ADMSCs and Cancer Cells in the Breast Tumor Microenvironment
Pharmaceutics | November 2023
Our study showed that curcumin is a potent anti-cancer agent that can remodel the breast tumor microenvironment, thereby restricting the ADMSC-cancer positive feedback loop associated with the CXCL12/CXCR4 axis. Curcumin is a natural polyphenolic compound derived from a turmeric plant (Curcuma longa). Its therapeutic effects against cancer have been well-documented, showing anti-cancer, anti-oxidative, and anti-inflammatory effects. Moreover, previous studies have suggested that curcumin can interfere with the metastasis of cancer cells by inhibiting the CXCL12/CXCR4 axis. We induced ADMSC transformation and verified that curcumin diminished the phenotypic change, inhibiting CAF marker expression. Additionally, curcumin suppressed the CXCL12/CXCR4 axis and its downstream signaling both in ADMSCs and MCF7 cells. The CM from ADMSCs, whose ADMSC-to-CAF transformation was repressed by the curcumin treatment. Through our research, it was demonstrated that curcumin is an effective modulator of breast TME. By disrupting the CXCL12/CXCR4 axis and the following NF-κB signaling pathway and EMT, curcumin alleviated the disease by mitigating the progression and metastasis of MCF7 and finally suppressing the positive loop formation within breast tumor microenvironment. These findings provide valuable insights into the therapeutic applications of curcumin and other flavonoids in treating cancer effectively in terms of tackling the tumor microenvironment.

Effects of curcumin/turmeric supplementation on the liver enzymes, lipid profiles, glycemic index, and anthropometric indices in non-alcoholic fatty liver patients: An umbrella meta-analysis
Phytotherapy Research | November 2023
Findings of 11 meta-analyses of 99 randomized controlled trials comprising 5546 participants revealed that curcumin/turmeric supplementation reduced AST (ES = −1.072, 95% CI (−1.656, −0.488), p = 0.000), ALT (ES = −0.625, 95% CI (−1.170, −0.134), p = 0.014), and TG (ES = −0.469, 95% CI (−1.057, 0.119), p = 0.128) levels, and HOMA-IR (ES = −0.291, 95% CI (−0.368, −0.214), p = 0.000), BMI (ES = −0.205, 95% CI (−0.304, −0.107), p = 0.000), and WC (ES = −1.290, 95% CI (−2.038, −0.541), p = 0.001) in comparison to the control group. The findings suggest the beneficial effects of curcumin/turmeric supplementation in patients with NAFLD, such as improving liver function, decreasing serum TG levels, ameliorating insulin resistance, and reducing general and central obesity.

Apoptosis antagonizing transcription factor-mediated liver damage and inflammation to cancer: Therapeutic intervention by curcumin in experimental metabolic dysfunction associated steatohepatitis-hepatocellular carcinoma
Journal of Cellular Physiology | November 2023
Curcumin treatment also suppressed hepatic expression of inflammatory, fibrogenic, and oncogenic markers. Of note, there was a significant reduction in the expression of AATF upon curcumin treatment in WDSW/CCl 4 mice and human HCC cells. In contrast, curcumin upregulated Kruppel‐like factor 4 (KLF4) in MASH liver and HCC cells, which is known to downregulate sp1 (specificity protein‐1) expression. Thus, curcumin treatment effectively inhibited the progression of MASH to HCC by downregulating the expression of AATF via the KLF4‐Sp1 signaling pathway. These preclinical findings establish a novel molecular connection between curcumin and AATF in reducing hepatocarcinogenesis, and provide a strong rationale for the development of curcumin as a viable treatment for MASH‐HCC in humans.

Curcumin's Dose-Dependent Attenuation of Gastric Cancer Cell Progression Via the PI3K Pathway Blockade
Dose-Response | November 2023
Curcumin, a polyphenolic compound found in turmeric (Curcuma longa), has demonstrated potential in multiple cancer types due to its anti-cancer characteristics. Curcumin, the main bioactive component of turmeric (C longa), has been widely studied for its anti-inflammatory, antioxidant, and anti-cancer properties. Mounting evidence suggests that curcumin may modulate various cellular pathways involved in the initiation, progression, and metastasis of different cancer types, including gastric cancer. Curcumin's potential health benefits and clinical applications cover a broad range of medical conditions, such as Alzheimer's disease, cardiovascular diseases, and diabetes, among others. Its anti-cancer effects have been demonstrated in numerous in vitro and in vivo studies, as well as in preliminary clinical trials.  Curcumin has been found to exert its anti-cancer activity through several mechanisms, including apoptosis induction, cell cycle arrest, angiogenesis inhibition, and suppression of invasion and metastasis.  Emerging evidence suggests that curcumin may inhibit gastric cancer cell progression by modulating the PI3K signaling pathway. The study findings demonstrate that curcumin treatment leads to a significant reduction in gastric cancer cell proliferation, migration, and invasion. These results are consistent with previous research on curcumin's anti-cancer properties in various cancer types. One of the critical mechanisms by which curcumin may exert its anti-cancer effects is through the inhibition of the PI3K signaling pathway, which plays a vital role in regulating cell growth and survival. Collectively, these studies demonstrate the diverse and multifaceted mechanisms through which curcumin exerts its effects on gastric cancer cells. Each study focuses on distinct signaling pathways, shedding light on different aspects of curcumin's therapeutic potential. Curcumin, a polyphenolic compound derived from the turmeric plant (C longa), has been extensively studied for its health benefits, including anti-inflammatory, antioxidant, and anti-cancer activities. The anti-cancer potential of curcumin has been demonstrated in various cancer types, including gastric cancer. Curcumin has been shown to inhibit cell proliferation, induce apoptosis, and suppress angiogenesis, metastasis, and invasion in different cancer models. The anti-cancer effect of curcumin is attributed to its multifaceted and intricate molecular mechanisms. Curcumin exerts its anti-cancer properties by targeting various signaling pathways involved in cell growth, survival, invasion, and metastasis. One of its central mechanisms is the inhibition of the PI3K/Akt/mTOR pathway, which is crucial for cell proliferation and survival. By blocking this pathway, curcumin suppresses cancer cell growth and induces apoptosis. Moreover, curcumin modulates the expression of key genes and proteins related to cell cycle regulation, such as p53 and cyclin-dependent kinases (CDKs), leading to cell cycle arrest and preventing uncontrolled cell division. Curcumin also exhibits anti-angiogenic effects, inhibiting the formation of new blood vessels necessary for tumor growth and metastasis. Additionally, it interferes with various pro-survival and pro-metastatic molecules, including matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), and nuclear factor-kappa B (NF-κB), thus limiting cancer cell invasion and metastasis. Furthermore, curcumin's antioxidant properties neutralize free radicals and reduce oxidative stress, which can contribute to cancer development. Overall, the diverse and comprehensive mechanisms of curcumin's anti-cancer activity make it a promising candidate for further exploration and development in cancer therapy.  Our study presents significant clinical relevance. Curcumin treatment led to a dose-dependent decrease in cell viability, migration, and invasion in gastric cancer cells, accompanied by downregulation of key PI3K signaling genes and proteins. This suggests curcumin's potential as a targeted therapeutic agent against gastric cancer, particularly when the PI3K pathway is dysregulated. The dose-dependent nature of curcumin's effects could allow for targeted inhibition of cancer cell progression while minimizing adverse effects on normal cells. In conclusion, the findings from this study suggest that curcumin may be a promising therapeutic agent for gastric cancer treatment, partly due to its inhibitory effects on the PI3K signaling pathway.

Curcumin Attenuates Ferroptosis and Ameliorates Erectile Function in Diabetic Rats by Activating Nrf2/HO-1 Pathway
Andrologia | November 2023
Turmeric-derived polyphenol derivative, curcumin, has been found to be effective in treating cardiovascular diseases. It has been found to improve aortic sclerosis by decreasing the production of peroxides and increasing the expression of the antioxidant manganese-containing superoxide dismutas. Furthermore, in experiments involving a high-fat diet, curcumin has been observed to reduce the increase of vascular oxidative stress levels caused by the diet. Curcumin treatment has been shown to be effective in improving erectile function and related tissue and molecular changes in diabetic rats. Furthermore, in vitro experiments have confirmed that curcumin can inhibit the occurrence of ferroptosis in penile endothelial cells that are stimulated by high glucose through Nrf2/HO-1 signaling. Curcumin has been found to improve the occurrence of penile ED in diabetic penile endothelial cells. In recent years, curcumin has gained popularity in the treatment of vascular diseases due to its anti-inflammatory and antioxidative properties. Our findings align with previous studies that have shown curcumin’s ability to effectively reduce tissue oxidative stress levels and protect the erectile function of diabetic rats.Furthermore, the results indicate that curcumin can enhance the erectile function of diabetic rats by inhibiting ferroptosis in the corpus cavernosum.

Curcumin Induces Apoptosis by Suppressing XRCC4 Expression in Hepatocellular Carcinoma
Nutrition and Cancer | November 2023
Curcumin exerts anti-cancer effects by inhibiting cell proliferation and promoting cell apoptosis in  hepatocellular carcinoma HCC. Curcumin is a chemical with various pharmacological activities used for cancer treatment. It inhibits hepatocellular carcinoma by inducing apoptosis. Compared with the control group, curcumin significantly promoted the apoptosis of  hepatocellular carcinoma cells in vitro and in vivo. Immunohistochemical analysis revealed that curcumin downregulated XRCC4 expression levels in  hepatocellular carcinoma tissues. This may be due to curcumin interference in the repair process of the nonhomologous DNA terminal link of  hepatocellular carcinoma cells by downregulating XRCC4 expression.

The Dose-Dependent Effect of Curcumin Supplementation on Inflammatory Response and Gut Microbiota Profile in High-Fat Fed C57BL/6 Mice
Molecular Nutrition & Food Research | November 2023
Curcumin, a polyphenol extracted from Curcuma longa L., exhibits anti-inflammatory activity. The study aims to investigate the effects of curcumin supplementation in different doses on the biochemical profile, inflammatory response, and gut microbiota profile in mice that are fed with high-fat diet (HFD).Curcumin increases the IL-10 protein expression in the white adipose tissue. In the liver, there is a reduction in tumor necrosis factor alpha (TNF-α) and an increase in IL-10 gene expression. Also, curcumin promotes the growth of butyrogenic bacteria, such as Clostridium clusters IV and XIVa.The findings suggest that curcumin has the potential to improve the inflammatory response and modulate healthy gut microbiota. Further studies are needed to clarify the role of curcumin as a preventive and effective strategy for obesity.

The Potential Mechanism of Curcumin in Treating Oral Squamous Cell Carcinoma Based on Integrated Bioinformatic Analysis
International Journal of Genomics | November 2023
Curcumin is a polyphenolic compound derived from the rhizomes of Curcuma longa, which serves as the primary bioactive constituent of turmeric. Curcumin has been extensively used in traditional Chinese medicine to treat various conditions, such as inflammation, pain, wounds, and gastrointestinal disorders. Contemporary research has unveiled many pharmacological properties of curcumin, encompassing antioxidant, anti-inflammatory, antimicrobial, and anticancer activities. Importantly, the potential anticancer effect of curcumin has been explored in diverse cancer types, including breast, colon, lung, prostate, and Oral Squamous Cell Carcinoma. Curcumin, the principal constituent of turmeric, has exhibited potential antitumor properties in clinical trials targeting malignancies such as hepatic, colorectal, and mammary neoplasms. In this study, we used a network pharmacology strategy to explore the potential mechanisms underlying the effect of curcumin on Oral Squamous Cell Carcinoma.

Antiviral and immunoregulatory effects of curcumin on coxsackievirus B3-infected hepatitis
Virus Research | October 2023
Curcumin exhibits anti-inflammatory and antiviral characteristics in inflammatory and infectious diseases. Several studies suggest that curcumin exhibits many beneficial pharmacological properties, including antioxidant, anti-inflammatory, antiangiogenic, and antimicrobial properties. Curcumin can modulate the nuclear factor to reduce the oxidative stress in liver injury, diabetes, nervous system diseases, and pulmonary diseases in vivo (Ghafouri-Fard et al., 2022; Ke et al., 2020; Liu et al., 2015). It can also decrease inflammatory levels of cytokines, including TNF-α, IL-6, and IL-1β, to inhibit tumor invasion and metastasis in several types of carcinoma and chronic diseases (Giordano and Tommonaro, 2019; Gonzales and Orlando, 2008). Additionally, curcumin possesses antiviral activities to inhibit hepatitis C virus (HCV), enterovirus 71 (EV71), human immunodeficiency virus (HIV)−1, herpes simplex virus (HSV)−2, and influenza A virus infections by regulating actin filament organization and blocking the protein kinase B (Akt) and nuclear factor-κB (NF-κB) pathways (Dai et al., 2018; Ferreira et al., 2015; Kim et al., 2010; Qin et al., 2014). Curcumin exhibited immunoregulatory and antiviral characteristics to reduce CVB3-induced hepatitis. Curcumin reduced the CPE and liver enzyme levels of CVB3-infected Huh-7 cells. In the animal studies, curcumin increased the survival rate and reduced the clinical severity of CVB3-infected mice. In the liver sections, we observed that curcumin improved the liver damage induced by CVB3 infection. Both in vitro and in vivo studies showed that curcumin can effectively increase HO-1 levels and reduce cleaved caspase-3 levels in human liver cell lines and the liver of CVB3-infected mice. Therefore, curcumin is a potential therapeutic option for CVB3-infected hepatitis clinically.

Evaluation of the protective effects of curcumin-rich turmeric (Curcuma longa) extract against isotretinoin-induced liver damage in rats
Toxicology Mechanisms and Methods | October 2023
Our results showed that ALT, AST, and MDA levels increased, and SOD and GSH levels decreased in the ISO-administered group compared to the healthy control group. curcumin 50, 100, and 200 mg/kg groups were compared to ISO group. A dose-dependent increase in protective effect was observed. A decrease in ALT, AST, and MDA levels, and an increase in SOD and GSH levels were determined. A protective effect was found at all doses. The best protective effect was in the CRT 200 mg/kg group. Curcumin extract can be considered a candidate herbal medicine for the elimination of liver damage in individuals using ISO. However, further experimental and clinical validation should be studied.

Curcumin and turmeric extract inhibited SARS-CoV-2 pseudovirus cell entry and Spike mediated cell fusion
bioRxiv | October 2023
Turmeric extract (TE) with curcumin as its main active ingredient has been studied as a potential COVID-19 therapeutic. Based on our study, both TE and curcumin are potential inhibitors of SARS-CoV-2 infection at entry points, either by direct or indirect infection models. Curcumin can interact with SARS-CoV-2 Spike RBD  (Shanmugarajan et al., 2020), hACE2 (Subbaiyan et al., 2020), and TMPRSS2 as well  (Motohashi et al., 2020). These data align with our results that curcumin inhibited PSV entry  and syncytia formation. Curcumin is capable of interfering with the Spike-receptor binding  either during direct viral infection or intercellular transmission, which hinders viral infection  and cell fusion (Marin-Palma et al., 2021). In addition, TE as the crude extract which contains curcumin also has the potential to inhibit SARS-CoV-2 infection and potentially to be  developed as an independent herbal-derived product for prevention of viral infection with curcuminoids used as identity compounds for TE standardization.

Effects of curcumin/turmeric supplementation on glycemic indices in adults
Diabetes & Metabolic Syndrome: Clinical Research & Reviews | October 2023
Out of 4182 articles retrieved from the initial search, 59 RCTs were included. Our findings suggested that turmeric/curcumin supplementation was significantly effective in improving fasting blood sugar, fasting insulin levels, and homeostatic model assessment of insulin resistance. Conclusion Our results indicate that turmeric/curcumin supplementation can be considered as a complementary method in the management of disturbed glycemia.

Effect of Turmeric Herbal on Polycystic Ovary Syndrome: A Systematic Review
International Journal of Current Science Research and Review | October 2023
One of the herbal medicines to treat PCOS is turmeric or curcumin. Curcumin has various biological activities including antioxidant, anti-inflammatory, anti-microbial, anti-tumor, cardioprotective and neuroprotective effects involving various mechanisms. Curcumin can stimulate insulin-mediated glucose uptake via the phosphatidylinositol 3-kinsase (PI3K)/Akt pathway, which, in turn, upregulates glucose transporter 4 (GLUT4) in adipocytes and skeletal muscle, leading to increased glucose levels. Curcumin supplementation improves glycemic control and lipid metabolism, and reduces oxygen radical species in PCOS patients. Curcumin is a diarylheptanoid derived from the rhizome of the Curcuma longa plant, which functions as an anti-inflammatory and antioxidant which is very important in the treatment of PCOS.

Curcumin inhibits the development of colorectal cancer via regulating the USP4/LAMP3 pathway
Naunyn-Schmiedeberg's Archives of Pharmacology | September 2023
In this study, we aimed to explore the effects of curcumin on the progression of colorectal cancer and its underlying mechanisms involved. Curcumin significantly accelerated cell apoptosis, and inhibited cell proliferation and invasion in LoVo and HCT-116 cells. LAMP3 was augmented in colorectal cancer tissues and cells, and curcumin could reduce the expression of LAMP3. Curcumin decreased LAMP3 expression to exhibit the inhibition role in the progression of colorectal cancer. Curcumin downregulated USP4 to impeded the progression of colorectal cancer via repressing LAMP3 expression. In addition, curcumin obviously restrained tumor growth in mice through downregulating USP4 and LAMP3 expression. These data indicated that curcumin exert the anti-tumor effects on the development of colorectal cancer through modulating the USP4/LAMP3 pathway.

This spice treats indigestion just as well as prescription drugs
New York Post | September 2023
Turmeric is derived from the root of the Curcuma longa plant, a type of ginger. The root contains curcumin, a compound known to have anti-inflammatory and antimicrobial properties. It’s long been used as an herbal remedy throughout Asia, but there have never been any head-to-head studies comparing turmeric to a prescription drug for indigestion — until now. Researchers from Thailand’s Chulalongkorn University enrolled 151 people with recurring indigestion (functional dyspepsia) in a study comparing the curcumin found in turmeric to omeprazole, commonly known as Prilosec. “Oral curcumin was found to be safe and well tolerated. Patients with functional dyspepsia treated with curcumin, omeprazole and curcumin plus omeprazole had similar significant symptomatic improvement,” the study authors wrote. There is a large growing body of medical evidence pointing to the health benefits of turmeric and curcumin, many of which are based on the spice’s anti-inflammatory and antioxidant properties. In a study of people with ulcerative colitis (a type of inflammatory bowel disease), those who took 2 grams of curcumin a day along with prescription drugs were more likely to have their symptoms stay in remission than people who took the drugs alone. It may also lower the risk of heart disease, according to the Cleveland Clinic: Among healthy adults who took curcumin supplements for 12 weeks, resistance artery endothelial production — which is linked to high blood pressure — was improved. Some research also suggests that curcumin may protect those at risk for heart disease by lowering certain levels of cholesterol. And among people who had coronary artery bypass surgery, those who took 4 grams of curcumin a day had a 65% lower risk of having a heart attack. And if that isn’t enough, there are numerous studies that find turmeric and curcumin can play a role in fighting depression, preventing cancer, improving memory and lessening the pain from arthritis and other conditions.As more research is done on the health benefits of turmeric and curcumin, the spice may move into mainstream medicine. As the authors of the indigestion study wrote, “the new findings from our study may justify considering curcumin in clinical practice.”

Long-term oral administration of curcumin is effective in preventing short-term memory deterioration and prolonging lifespan in a mouse model of Alzheimer’s disease
Advances in Traditional Medicine | September 2023
Curcumin has been shown to have the potential to ameliorate or prevent the development of Alzheimer's disease. Survival rate was 34% in the Alzheimer's disease control group, 100% in the 0.02% curcumin, and 83% in the 0.5% curcumin group, significantly longer in the curcumin groups than the Alzheimer's disease control group. This study demonstrates that long-term intake of low concentrations of curcumin may act on the tau-phosphorylation, suppress brain inflammation, delay the onset of Alzheimer's disease, and prolong the lifespan of the mouse.

Turmeric may be as good for treating indigestion as drug to curb excess stomach acid
British Medical Journal | September 2023
Turmeric is derived from the root of the Curcuma longa plant. It contains a naturally active compound called curcumin thought to have anti-inflammatory and antimicrobial properties, and has long been used as a medicinal remedy, including for the treatment of indigestion. SODA scores indicated significant reductions in symptom severity by day 28 for pain (−4.83, –5.46 and −6.22) and other symptoms (−2.22, –2.32, and −2.31) for those in the combined, curcumin alone, and omeprazole alone groups, respectively. These improvements were even stronger after 56 days for pain (−7.19, –8.07 and −8.85, respectively) and other symptoms (−4.09, –4.12 and −3.71, respectively). SODA also captures satisfaction scores: these scarcely changed over time among the curcumin users, which might possibly be related to its taste and/or smell, suggest the researchers. No serious side effects were reported, although liver function tests indicated some level of deterioration among curcumin users carrying excess weight, note the researchers. They acknowledge the small size of the study, as well as several other limitations, including the short intervention period and lack of long-term monitoring data. Further larger, long term studies are needed, they say. Nevertheless, they conclude: “This multicentre randomised controlled trial provides highly reliable evidence for the treatment of functional dyspepsia,” adding that "the new findings from our study may justify considering curcumin in clinical practice."

Curcumin extends the lifespan of aging postmitotic cells with mitochondrial dysfunction
bioRxiv Cold Spring Harbor Laboratory | September 2023
Curcumin, a natural compound, is explored for its anti-aging potential. This study explores the influence of curcumin on the postmitotic cellular lifespan (PoMiCL) of yeast during chronological aging, examining its potential implications for age-related diseases. Our findings reveal that curcumin significantly extends the lifespan of postmitotic wildtype yeast cells, with maximal effects observed at lower concentrations, displaying a hormetic response. Importantly, curcumin mitigates accelerated aging in cells afflicted by mitochondrial dysfunction. These findings shed light on curcumin’s potential as an anti-aging modulator and its relevance to age-related diseases, offering insights into novel therapeutic approaches for healthy aging while highlighting the context-dependent nature of its effects.  Recent research has drawn attention to the potential impact of curcumin, a polyphenolic bioactive compound derived from the rhizome of Curcuma longa (turmeric), for its therapeutic potential across a wide spectrum of diseases including mitigating the effects aging and increasing lifespan. Two groundbreaking observational cohort studies conducted among middle-aged and older Asian adults living in Singapore have revealed an intriguing connection between the consumption of curcumin-rich foods and healthspan. This study represents the inaugural longitudinal exploration of the cognitive advantages linked to curcumin obtained from natural dietary sources in human subjects. The results emphasize the potential health and longevity-enhancing effects of curcumin in the diet from natural sources, providing valuable insights into how consuming curry may affect various health aspects, including cognitive benefits over time and the potential to extend the lifespan of patients with cardio-metabolic and vascular diseases. Our results demonstrate that curcumin has a significant impact on extending the lifespan of postmitotic cells during chronological aging. These findings align with previous studies that have highlighted the beneficial effects of curcumin on healthspan and cellular longevity. Notably, curcumin’s anti-aging effects exhibit a biphasic dose-response pattern, with lower concentrations showing greater efficacy. This hormetic effect of curcumin on cellular lifespan, observed both in yeast and human cells, adds an intriguing dimension to its potential as an anti-aging intervention. In summary, our study provides valuable insights into the intricate relationship between curcumin, postmitotic cellular aging, and mitochondrial function. It demonstrates that curcumin has the potential to extend the lifespan of postmitotic cells, with its effectiveness influenced by concentration and the presence of mitochondrial dysfunction. These findings contribute to our understanding of curcumin’s role as a potential modulator of cellular aging and emphasize the importance of considering dosage and cellular context when exploring its therapeutic applications. While this research represents a significant step forward, further investigations are needed to elucidate the precise molecular mechanisms underlying curcumin’s effects on cellular lifespan and to translate these findings into potential therapeutic interventions for human aging and age-related diseases.

Curcumin and proton pump inhibitors for functional dyspepsia: a randomised, double blind controlled trial
BMJ Evidence-Based Medicine | September 2023
Curcumin and omeprazole had comparable efficacy for functional dyspepsia with no obvious synergistic effect. Turmeric, scientifically known as Curcuma longa L., has a long history of extensive use. This plant has a valuable active compound, curcumin, which is used both topically and orally for medicinal purposes. While curcumin is commonly found in nourishing creams and cosmetics, it is also available in the form of powder capsules used for treating various gastrointestinal problems, including dyspepsia. Recent findings from a Cochrane review suggested that curcumin may offer moderate improvement in dyspepsia symptoms compared with placebo. Curcumin, extracted from turmeric, is a hydrophobic polyphenol with a low molecular weight. This compound exhibits a broad range of biological properties, such as anti-inflammatory, anti- oxidant, antiproliferative and antimicrobial properties. Several clinical trials have established the pharmacological properties of curcumin. Curcumin is effective in the treatment of gastric ulcers, erosions and dyspepsia,  with ulcers and erosions reduced or even eradicated after administration of curcumin (3000 mg/day) for up to 12 weeks, while abdominal pain and discomfort were significantly reduced. Similarly to the findings of the current study, curcumin has been shown to be safe in numerous human studies, with only minor toxicity associated with this polyphenol. Therefore, curcumin is increasingly being viewed as a biomolecule capable of being administered for an extended period without causing adverse effects. The findings of the current study indicate that there were no significant adverse events associated with the short term use of PPI and curcumin. This study represents the first head-to- head comparison demonstrating the efficacy of curcumin in treating functional dyspepsia compared with omeprazole. Curcumin was effective in all subtypes of functional dyspepsia. Curcumin and omeprazole were both effective for functional dyspepsia.

Safety and Efficacy of Turmeric (Curcuma longa) Extract and Curcumin Supplements in Musculoskeletal Health: A Systematic Review and Meta-Analysis
Alternative Therapies In Health And Medicine | September 2023
Curcuma longa is a rhizomatous, herbaceous, perennial herb belonging to the ginger family and has a broad variety of biological properties, such as antioxidant, anti- inflammatory, antimutagenic, antimicrobial, and anticancer properties. 4,5 These properties belong to the bioactive principles in the rhizomes, the hydrophobic polyphenols called curcuminoids, which comprise curcumin, demethoxycurcumin, and bisdemethoxycurcumin, of which curcumin—1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6- heptadiene-3,5-dione—is the major natural polyphenol. Curcuminoids, commonly called curcumin, have been shown to exhibit a broad spectrum of pharmacological actions proven in several in-vitro and in-vivo studies as well as in clinical trials. Curcumin has also been recognized as safe by the US Food and Drug Administration (FDA). The effects of curcumin on joint health and these disorders have been evaluated in several clinical trials pertaining to its potent anti-inflammatory action. The current meta-analysis has demonstrated the effectiveness of curcumin in improving joint health. Several studies have reported that curcumin is safe and effective for various joint health conditions, such as joint pain, osteoarthritis and rheumatoid arthritis.

 Turmeric might help treat your indigestion, study shows
CNN | September 2023
“In addition to anti-inflammatory and antioxidant purposes, curcumin/turmeric could be an option for treating dyspepsia with comparable efficacy to omeprazole,” said lead study author Dr. Krit Pongpirul, associate professor in the department of preventive and social medicine at Chulalongkorn University in Bangkok. It makes sense that research would investigate turmeric’s impact on indigestion, because its compound curcumin has been studied in a wide variety of inflammatory conditions, including inflammatory bowel disease and arthritis, said Dr. Yuying Luo, a gastroenterologist and assistant professor of gastroenterology at the Icahn School of Medicine at Mount Sinai in New York City. Some studies have shown that curcumin was helpful in conjunction with other medications, she added.

Cytotoxicity of curcumin against CD44± prostate cancer cells
Avicenna Journal of Phytomedicine | September 2023
Our findings indicate that curcumin, by promoting the expression of tumor suppressors, miR-383-5p and miR-708-5p, and inhibiting their target genes, induced its cytotoxicity against CD44± PC cells. We trust that curcumin could be established as a promising adjuvant therapy to current prostate cancer  treatment options following more research in clinical settings. Curcumin is a phytochemical product whose anti-prostate cancer effects on the inhibition of proliferation, invasion, cellular adhesion, and angiogenesis of many tumors have been confirmed (Termini et al., 2020). Multiple studies have shown that curcumin and its analogs have promising potential to target CSCs (Li and Zhang, 2014; Ramasamy et al., 2015). Altogether, our study revealed that curcumin suppressed cellular proliferation and induced apoptosis in CD44+ and CD44- PC cells. We also showed that curcumin, by promoting the expression of miR-383 and miR-708 and inhibiting their target genes, induced its cytotoxicity against CD44± PC cells. Considering that traditional cancer chemotherapeutic agents and radiotherapy cannot eradicate CSCs, the cytotoxicity of curcumin against CD44+ human prostate CSCs is a remarkable feature. We trust that curcumin could be established as a promising adjuvant to current PC treatment options following research in clinical settings.

Turmeric could be as effective as medicine for indigestion, says study
The Guardian | September 2023
Turmeric contains a naturally active compound called curcumin, thought to have anti-inflammatory and antimicrobial properties. It has long been used as a medicinal remedy, including for the treatment of indigestion, in south-east Asia.Researchers found that oral curcumin was safe and well tolerated, and that patients in all three groups experienced a similar improvement in symptoms. “This multi-centre randomised controlled trial provides highly reliable evidence for the treatment of functional dyspepsia,” adding that “the new findings from our study may justify considering curcumin in clinical practice”.

Curcumin: recent updates on gastrointestinal cancers
CyTA - Journal of Food | September 2023
Curcumin shows multispectral anticancer effects and recent studies have explored its mechanism of action to design and develop anticancer therapies. In gastrointestinal cancer cells, curcumin has been shown to induce cell death through apoptosis and to cause cell cycle arrest. Additionally, curcumin prevents DNA from replication during the S phase. It has been reported that tumors can be reduced at different stages of the cell cycle using curcumin. It blocks various enzymes that participate in the growth and development of tumors and may resist tumor treatment. Furthermore, curcumin also modulates cellular progressions, i.e., protein kinase C activity, EGF (epidermal growth factor) receptor intrinsic kinase activity, nuclear factor kappa (NF-kB) activity, nitric oxide synthesize activity, and suppresses lipid peroxidation (Imran et al., Citation2018). Curcumin, a plant-derived polyphenol, has been identified as a therapeutically effective food that exhibits pleiotropic pharmacological effects on a variety of malignancies (Lim, 2022). Curcumin has an anti-tumor role in gastric cancer cells via inhibiting invasion and proliferation and inducing apoptotic cell death in experimental subjects (Kwiecien et al., 2019). Curcumin has been chosen by the National Cancer Institute as a third-generation cancer chemo preventive drug (Abd El‐Hack et al., 2021). In different in vivo and in vitro studies, curcumin has exhibited anticancer effects involving mechanisms such as reduction in the formation of liver tumors, suppression of metastasis of primordial germ cell (PGC), CXCR4 expression, and inhibition of stromal cell-derived factor-1/CXCR4 signaling (Gu et al., 2019). Furthermore, curcumin suppresses the p-Akt protein expression, increments in PTEN expression, and reduction in miR-21 levels. It also shows suppression of STAT3 phosphorylation, blocked STAT3-mediated signaling, induction of growth arrest, and apoptosis (Qiang et al., 2019). Curcumin has the effects of reducing the dosage, resistance and side effects of chemotherapy drugs, besides a pivotal role in the modulation of biological processes resulting in the prevention of cancer particularly due to its radical scavenging activities and other mechanisms (Zhou et al., Citation2011, Citation2017). Curcumin possesses anticancer effects against different human gastrointestinal cancer cell lines through various mechanisms. It suppresses the cell proliferation, invasion and propagation stages in different human cancer cell lines. Furthermore, its sole and co-administration exhibit different effects on cancer cells that make it an important compound to be used as a therapeutic agent in different nutraceutical and pharmaceutical formulations. In the near future, curcumin is anticipated to be proven as a novel drug to cure and treat several human gastrointestinal cancer cell lines.

A spice that gives curries its vibrant colour could be a cure for indigestion, research suggests
Daily Mail | September 2023
The spice that gives curry its yellow colour could be an unlikely cure for indigestion, research suggests. Scientists have discovered that turmeric – a common spice that many have in their kitchen cupboards – is as effective as a drug for treating symptoms. The golden-orange spice is derived from the root of the Curcuma longa plant and contains a naturally active compound called curcumin. This is thought to have anti-inflammatory and antimicrobial properties and has long been used as a medicinal remedy in South East Asia. ‘In th trial, oral curcumin was found to be safe and well tolerated. Patients with functional dyspepsia treated with curcumin, omeprazole and curcumin plus omeprazole had similar significant symptomatic improvement.’ Turmeric is also believed to help fight off infection, protect against allergies, boost memory and lift our mood.

Curcumin protects from LPS-induced activation in the pathogenesis of neurological diseases and inflammatory responses
NueroReport | September 2023
Our data demonstrated that curcumin significantly increased the level of phosphorylated AMPK protein in LPS-activated astrocytes. In addition, our data demonstrated that curcumin play an inhibitory role on the migration, autophagy, the pro-inflammatory mediators by the AMPK signaling pathway in LPS-activated astrocytes. These results might contribute to a promising therapeutic intervention in the neurological diseases-related astrocytes activation. Curcumin , as a phenolic pigment extracted from curcuma longa, has been shown to suppress inflammatory response and anti-oxidant against the pathological changes in various neurological disorders. It is reported that curcumin could inhibit the inflammatory cytokines such as TNF-α, IL-1β, IL-6, and monocyte chemoattractant protein 1 (MCP-1). Additionally, curcumin exerts the anti-oxidant effect through nuclear factor erythroid 2-related factor 2 (Nrf2) pathways. Recent studies have revealed that curcumin acts as direct inhibition of astrocyte activity in neurodegenerative diseases and ischemic stroke. In summary, we provided evidence showing that curcumin markedly inhibited the proliferation of in LPS-activated astrocytes. Our results demonstrated that the inhibiting effects of the curcumin on migration, autophagy, the production of pro-inflammatory mediators, and the oxidative stress were mediated at least by the AMPK signaling pathway. Therefore, curcumin, a potent anti-oxidant, could be beneficial for ameliorating the neurological diseases-related astrocytes activation. What is more, our findings may provide a new molecular mechanism for the therapeutic effects of curcumin.

Turmeric May Fight Indigestion as Well as Some Medications, Study Finds
Prevention | September 2023
New research finds curcumin, the active compound in turmeric, was just as effective as common over-the-counter medications at treating indigestion.Researchers found no significant differences in the indigestion symptoms of people taking omeprazole, curcumin, or the combination of the two. (Those symptoms can include pain, a burning feeling, or discomfort in the upper abdomen, feeling uncomfortably full after a meal, or feeling full too soon while eating, per the National Institute of Diabetes and Digestive and Kidney Diseases, NIDDK). The researchers concluded that curcumin and omeprazole had “comparable efficacy” for chronic indigestion—meaning, they both worked about the same. The idea of using turmeric or curcumin for indigestion isn’t totally out there: Turmeric has been used in parts of Southeast Asia to treat stomach discomfort for years, says study co-author Krit Pongpirul, M.D., M.P.H., Ph.D., associate professor at Chulalongkorn University and an adjunct faculty member at the Johns Hopkins Bloomberg School of Public Health.Scientific research into curcumin for indigestion is still ongoing, but the compound may help tamp down acid production in the stomach, says Rudolph Bedford, M.D., a gastroenterologist at Providence Saint John’s Health Center in Santa Monica, CA. “Some people also use curcumin to treat pain that may be due to inflammation of some type,” he points out, noting that it’s possible the compound could help stomach pain from indigestion as well.

An Overview of the Enhanced Effects of Curcumin and Chemotherapeutic Agents in Combined Cancer Treatments
International Journal of Molecular Sciences | August 2023
Curcumin, a polyphenol, has been shown to have extensive cytotoxic functions against cancer cells, including combined treatment. In particular, we have described the results of recent preclinical and clinical studies exploring the pleiotropic effects of curcumin in combination with standard drugs and the potential to consider it as a promising new tool for cancer therapy. Curcumin, a yellow pigment of the spice turmeric Curcuma longa Linn, is one of the most studied phytochemicals used as anticancer molecules. This polyphenol has been used in traditional medicine in Asia since ancient times and it has been shown to have extensive cytotoxic effects against cancer cells. In addition, curcumin has also shown beneficial and protective functions in acute myocardial infarction and cardiovascular diseases, chronic atherosclerosis, neurodegenerative diseases and autoimmune diseases. Interest in curcumin has gradually increased after several studies demonstrated its chemotherapeutic and chemopreventive effects. Several studies have reported that curcumin is able to affect gene expression and trigger various signalling mediators such as NF-κB, COX-2, AP-1, EGFR, MMP9 and PKC, which are involved in several signalling pathways such as angiogenesis, survival, metastasis and proliferation. Curcumin has been reported to exert significant immunomodulatory activity and protect the immune system from cancer-related suppression. Since curcumin is able to modulate gene expression, in vitro studies have been conducted to investigate transcriptional modulation associated with the use of this phytochemical. Transcriptomic analyses performed after curcumin treatment in various cancer cells showed specific modulation of gene expression. Further analysis of microRNA expression showed that curcumin can also modulate various non-coding genes in different cellular contexts in human pancreatic cancer or  in non-small cell lung cancer. In addition, other studies have shown that curcumin can influence the epigenomic landscape, as it is able to induce specific methylation changes that are not determined by a direct effect on DNA methyltransferases but are a consequence of curcumin’s direct effect on modulating gene expression. As for the cytotoxic effects of curcumin in cancer, this ability is closely linked to the modulation of signalling pathways related to cancer, such as cell cycle, apoptosis, and resistance to multiple drugs. For example, curcumin has been reported to prevent colon cancer proliferation by blocking the cell cycle and accelerating apoptosis. In human colon cancer cells, curcumin significantly inhibited cell growth. It also triggered apoptosis via a mitochondria-mediated pathway. Curcumin induced the release of cytochrome c, significantly increased BAX and p53, and showed a marked reduction in BCL-2 and survivin in colorectal carcinoma LoVo cells. Moreover, curcumin was reported to significantly decrease the expression of cyclin D and inhibit the activity of p21-activated kinase1 (PAK1), leading to the suppression of gastric cancer cell proliferation and invasion.

Curcumin as a functional food in cancer
Molecular Mechanisms of Action of Functional Foods and Nutraceuticals for Chronic Diseases | August 2023
The correlation between various plant consumption and reduced cancer development has been well-established in many epidemiological studies. Among these, turmeric (Curcuma longa), or the “golden spice”, is a famous ingredient within the Indian sub-continent cooking and Ayurveda holistic medicine approach. The bioactive form of turmeric known as curcumin has been studied extensively in vitro and in vivo using a wide range of cancer types. Almost all studies confirmed not only remarkable anti-cancer activities but also selectivity and safety towards normal cells. The anti-cancer properties of curcumin were evident from the early stages of cancer initiation and remain effective even within highly aggressive metastatic cancer models. Such impacts were attributed to multi-targeted mechanisms of curcumin involving direct and indirect methods, signaling pathways, and molecular and biochemical targets.

Effects of curcumin on blood pressure: A systematic review and dose-response meta-analysis
Nutrition, Metabolism & Cardiovascular Diseases | August 2023
Curcumin has numerous biological activities and pharmacological effects, including anti-inflammatory, antioxidant, capabilities, and hepatoprotective effects. Subgroup analysis revealed a significant reduction only in DBP levels (WMD: -0.76 mmHg, 95% CI: -1.46,-0.05; P=0.03). Also, a significant reduction in SBP (WMD: -1.55 mmHg, 95% CI: -2.85, -0.25; P = 0.01) and DBP (WMD: -1.73 mmHg, 95% CI:-2.67, -0.79; P<0.01) was noticed by curcumin supplementation in studies that performed on women. The current study suggests that consuming curcumin may improve blood pressure when administered in long durations ≥ 12 weeks.

Combination of epigallocatechin 3 gallate and curcumin improves d-galactose and normal-aging associated memory impairment in mice
Scientific Reports  | August 2023
Curcumin improves aging-associated memory impairment in d-galactose (D-gal) and normal-aged mice. Curcumin and Epigallocatechin 3 gallate (EGCG) combination substantially reduced the oxidative stress that commonly mediates aging. The co-administration of EGCG and curcumin significantly increased retention time and remarkably ameliorated the levels of glutathione, superoxide dismutase, catalase, advanced oxidation protein products, nitric oxide, and lipid peroxidation compared to the monotherapy of EGCG or curcumin in mice hippocampi. The behavioral and biochemical studies revealed that the combination of EGCG and curcumin showed better improvement in rescuing aging-associated memory disorders in mice. EGCG and curcumin combination could serve as a better choice in managing aging-related memory disorders. improvements in behavioral endophenotype appear due to the antioxidant, anti-inflammatory, and anti-senescence properties of curcumin, shown in a previous study. Curcumin produces neuroprotective effects by exerting antioxidant, anti-aging, and anti-neuroinflammation properties. A study showed that curcumin protects memory from impairment in D-gal and NA-induced memory impairment by regulating degeneration, proliferation, and senescence of neuronal cells. Additionally, curcumin was found to improve cognitive dysfunction by increasing synaptic density in the AD animal.  We investigated the beneficial effects of EGCG and curcumin on oxidative stress in the two robust aging mice models by performing behavioral and biochemical studies. A combination of EGCG with curcumin exhibits greater protection from aging-related memory impairment by modulating oxidative stress biomarkers.

The beneficial effects of curcumin supplementation on blood lipid levels among patients with metabolic related diseases in Asia area: a systematic review and meta-analysis of randomized controlled trials
Frontiers in Sustainable Food Systems | August 2023
Numerous studies have shown that curcumin has a variety of pharmacological activities, including antibacterial, antitumour, anti-inflammatory, antioxidant, anticoagulant, and is particularly prominent in improving metabolic diseases (Asai and Miyazawa, 2001; Ejaz et al., 2009). Curcumin has been reported to promote weight loss, improve hyperlipidaemia, and reduce hepatic steatosis (Menon and Sudheer, 2007; Ak and Gülçin, 2008). In addition, curcumin has been shown to have therapeutic effects on various diabetic complications such as nephropathy and cardiovascular disease in patients with type 2 diabetes (Jeenger et al., 2015). A meta-analysis showed that curcumin supplementation also significantly reduced levels of inflammatory markers and biomarkers of oxidative stress in patients with Mets (Sun et al., 2022). Second, the potential mechanisms by which curcumin improves obesity and lowers blood lipids have received increasing attention. For example, curcumin blocks preadipocyte differentiation in vitro (Sakuma et al., 2017) and inhibits the expression of inflammatory cytokines in TNFα-stimulated adipocytes (Gonzales and Orlando, 2008). Curcumin also inhibits 3T3-L1 adipocyte differentiation and promotes preadipocyte apoptosis (Wu et al., 2019). Curcumin supplementation significantly reduced triglycerides, total cholesterol and low-density lipoprotein cholesterol but no effect on HDL. In the non-linear dose-response analysis, we observed a significant effect of curcumin supplementation dose on triglycerides levels (P-non-linearity = 0.022). In conclusion, curcumin may be beneficial in reducing triglycerides, total cholesterol and low-density lipoprotein cholesterol levels in the Asian populations with metabolic diseases. The dose of curcumin intervention may be an underlying factor influencing levels. The results of this meta-analysis may be useful in making recommendations for the use of curcumin as a dietary supplement.

 A review on curcumin colon-targeted oral drug delivery systems for the treatment of inflammatory bowel disease
 Inflammopharmacology | August 2023
The use curcumin is one such treatment option that has seen an increase in usage in treating inflammatory bowel disease. Curcumin is derived from a rhizome of turmeric (Curcuma longa), and the results of studies on the use of curcumin to treat inflammatory bowel disease are promising. These studies suggest that curcumin interacts with cellular targets such as NF-κB, JAKs/STATs, MAPKs, TNF-α, IL-6, PPAR, and TRPV1 and may reduce the progression of inflammatory bowel disease. Potentially, curcumin can be used as a therapeutic agent for patients with inflammatory bowel disease when it reduces the incidence of clinical relapse.

AATF-mediated Liver Damage and Inflammation to Cancer: Therapeutic Intervention by Curcumin in Experimental MASH-HCC
JSS Medical College | August 2023
Curcumin treatment suppressed hepatic expression of inflammatory, fibrogenic, and oncogenic markers. Of note, there was a significant reduction in the expression of AATF upon curcumin treatment in WDSW/CCl4 mice and human HCC cells. In contrast, curcumin upregulated Kruppel-like factor 4 (KLF4) in MASH liver and HCC cells, which is known to downregulate sp1 (specificity protein-1) expression. Thus, curcumin treatment effectively inhibited the progression of MASH to HCC by downregulating the expression of AATF via the KLF4-Sp1 signaling pathway. Curcumin, an active component of curcuminoids derived from the rhizome of turmeric (Curcuma longa, Zingiberaceae), is a diarylheptane and is known for its anti-inflammatory, antioxidant, and anti-cancer properties. Curcumin is known to mediate anticancer effects by modulating inflammatory cytokines, growth factors, transcription factors, and multiple signaling proteins. Several studies have shown the positive effects of curcumin on ameliorating MASH. Curcumin lowers de novo lipogenesis by reducing the levels of sterol regulatory element binding protein 1-c (SREBP-1c) and adipose differentiation-related protein (ADRP). In the streptozotocin (STZ)-induced MASH-HCC model, curcumin protected liver damage from ER stress and related inflammation. Studies have suggested that curcumin may help reduce liver inflammation and oxidative stress, which are key factors in the development and progression of MASH. Additionally, curcumin has been found to have beneficial effects on lipid metabolism, insulin resistance, gut microbiota, and fibrosis. In conclusion, the current study adds to the growing body of evidence supporting the promising role of curcumin and its potential applications in the prevention and treatment of MASH-HCC. We demonstrated that curcumin ameliorates AATF- mediated liver damage and inflammation to cancer in MASH-HCC via KLF4 and Sp1 signaling pathway. Furthermore, the study offers valuable insight into the potential benefits of curcumin for MASH-HCC, for which the development of effective therapeutic agents is an absolute necessity.

A Review on the Golden Plant Turmeric and Its Bioactive Compound Curcumin
Biosynthesis of Bioactive Compounds in Medicinal and Aromatic Plants | August 2023
Bioactive compounds like curcumin, identified in turmeric, are rich in therapeutics. In the last 10 years, research interests have concentrated on bioactive curcuminoid compounds (curcumin, demethoxy curcumin, and bisdemethoxy curcumin). In recent studies, curcumin  has been found to play a very effective role against cancer, biotic, inflammatory, and aging. The present study summarizes the pharmaceutical usages of turmeric with distinct reference to its polyphenolic compound curcumin.

Curcumin derived from medicinal homologous foods: its main signals in immunoregulation of oxidative stress, inflammation, and apoptosis
Frontiers in Pharmacology | August 2023
Curcumin, the primary component derived from medicinal homologous foods like curcuma longa rhizome, is reported to play vital actions in organic activities, such as the numerous pharmacological functions including anti-oxidative stress, anti-inflammation and anti/pro-apoptosis in treating various diseases. Due to its role in oxidative stress, inflammatory response, and apoptosis, curcumin shows significant pharmacological potential and has exhibited favorable effects concerning various metabolic disorders, immune-related diseases, and cancers. Growing experimental evidence revealed that curcumin had been shown to scavenge ROS, inhibit the production of pro-inflammatory cytokines, and modulate various signaling pathways involved in apoptosis. Furthermore, curcumin exhibits an excellent safety profile, with no significant adverse effects reported even at high doses. Curcumin, a bioactive compound present in turmeric, has emerged as a potential health-promoting agent in the regulation of various diseases. This mini-review offers a comprehensive summary of recent advances in elucidating the preventive and curative effects of curcumin on oxidative stress, inflammation, and apoptosis in non-cancerous diseases and cancers. Generally, curcumin exhibits its antioxidant property through AMPK/Nrf2/ARE/Keap1 pathway activation, its anti-inflammatory property via NF-κB/AP-1/MAPK pathways inhibition, and its anti-apoptosis property by blocking JAK/STAT and ER stress-induced pathways while activating PI3K/AKT/mTOR pathways in non-cancerous diseases. Conversely, curcumin demonstrates pro-oxidant, anti-inflammatory, and pro-apoptosis properties in cancers.

Lysosomes, curcumin, and anti-tumor effects: how are they linked?
Frontiers in Pharmacology | August 2023
Curcumin is a natural active ingredient from traditional Chinese medicine (TCM) that has multi-target characteristics to exert extensive pharmacological activities and thus has been applied in the treatment of various diseases such as cancer, cardiovascular diseases, nervous system, and autoimmune disorders. Curcumin, an orange-yellow polyphenolic compound originating from TCM, has attracted much attention owing to its anti-inflammatory, anti-bacterial, anti-oxidant, and other biological activities. Many studies have focused on the anti-tumor activity of curcumin. It has been illustrated that curcumin can exert an anti-tumor effect by modulating growth factors, enzymes, transcription factors, kinases, inflammatory cytokines, and pro- and anti-apoptotic proteins. Curcumin has anti-inflammatory, anti-diabetic, anti-tumor and anti-aging therapeutic potential and is widely used in various diseases such as cancer, cardiovascular disease, neurological and autoimmune (Raghav et al., 2021). The anti-tumor mechanisms of curcumin are diverse, but recent studies have shown that curcumin and its related derivatives can regulate their biological functions by targeting the lysosomal pathway, thereby exerting anti-tumor effects. Curcumin can mediate lysosomes to regulate cellular energy metabolism and lysosome biogenesis, inhibit tumor cell proliferation or promote tumor cell apoptosis, and play an anti-tumor effect. Lysosome itself or various CTS secreted by it can also enhance tumor invasion and metastasis by promoting tumor EMT or tumor angiogenesis, while curcumin can inhibit the above processes. In addition, curcumin can also reverse the MDR mediated by lysosomes and improve the anti-tumor effect of chemotherapy drugs. Finally, curcumin has a positive immunomodulatory effect on the body by regulating lysosome-induced immune dysfunction and immune checkpoint inhibition.

The Beneficial Effects of Curcumin on Lipids: Possible Effects on Dyslipidemia-Induced Cardiovascular Complications
Current Medicinal Chemistry | August 2023
Recent evidence suggest that curcumin may improve lipid metabolism and prevent dyslipidemia-induced cardiovascular complications via several pathways. Although the exact molecular mechanisms involved are not well understood, the evidence presented in this review suggests that curcumin can provide significant lipid benefits via modulation of adipogenesis and lipolysis, and prevention or reduction of lipid peroxidation and lipotoxicity via different molecular pathways. Curcumin can also improve the lipid profile and reduce dyslipidemia-dependent cardiovascular problems by impacting important mechanisms of fatty acid oxidation, lipid absorption, and cholesterol metabolism.

Curcumin inhibits esophageal squamous cell carcinoma progression through down-regulating the circNRIP1/miR-532-3p/AKT pathway
Environmental toxicology | August 2023
Curcumin shows an anti-cancer role in many kinds of tumors. Curcumin could time- and dose-dependently inhibit esophageal squamous cell carcinoma cells activity. Additionally, ESCC cells exposed to 20 μM of curcumin exhibited significantly decreased proliferative and invasive capacities, as well as enhanced cell apoptosis. Exposure to 10–20 μM of curcumin inhibited circNRIP1 expression. Curcumin inhibited AKT phosphorylation by up-regulating miR-532-3p expression, thereby inhibiting the activation of the AKT pathway. In summary, curcumin is a potent inhibitor of esophageal squamous cell carcinoma growth, which can be achieved through the regulation of the circNRIP1/miR-532-3p/AKT pathway. This research may provide new mechanisms for curcumin to inhibit the malignant development of esophageal squamous cell carcinoma.

 Male and Female Breast Cancer and the Effect of Medicinal Plants
Medium.com | August 2023
Curcumin has garnered significant interest from researchers due to its potential anti-cancer properties. It targets multiple pathways and prevents molecular deregulation, leading to reduced cancer growth. In breast cancer, curcumin has demonstrated various anti-cancer activities, suppressing tumor cell growth, inhibiting cancer invasion, and impeding metastasis. It plays a crucial role in promoting cancer cell death, minimizing inflammation, and slowing down tumor growth. Curcumin’s beneficial effects on breast cancer involve its action on several signaling pathways. It suppresses the activity of MMP (Matrix Metalloproteinase) genes, inhibits cell proliferation in triple-negative breast cancer cells via the EGFR (Epidermal Growth Factor Receptor) — MAPK (Mitogen-Activated Protein Kinases) signaling pathway, and hinders cell migration and invasion through the TGF-beta/Smad pathway and the Akt/SKP2 signaling pathway. Moreover, curcumin enhances sensitivity to tamoxifen, a commonly used breast cancer treatment, and induces apoptosis, or programmed cell death, in breast cancer cells. Lastly, it has shown the ability to reduce metastatic activity in estrogen receptor-negative breast cancer cells. Overall, curcumin’s multifaceted actions make it a promising candidate for further exploration as a potential therapeutic agent in breast cancer treatment.

The effect of curcumin-piperine on cardiometabolic, inflammatory and oxidative stress factors and macular vascular density in optical coherence tomography angiography (OCTA) in patients
Avicenna Journal of Phytomedicine | August 2023
Curcumin is a safe phytochemical with antioxidant, anti-inflammatory, antidiabetic, and lipid-lowering effects. Curcumin, the biologically active substance in turmeric, is a low molecular weight hydrophobic flavonoid with numerous health benefits including antioxidant and anti-inflammatory activities (Jeenger et al., 2015; Neerati et al., 2014; Mohajeri et al., 2020; Parsamanesh et al., 2018; Farhood et al., 2019; Gorabi et al., 2019; Mortezaee et al., 2019; Shakeri et al., 2019). No significant adverse effects are associated with supplementation with curcumin, even at doses above 8 g/day (Mirzaei et al., 2017). Many regulatory proteins, including chemokines, interleukins, hematopoietic growth factors, and transcription factors, are modulated by curcumin, thus reducing the inflammatory process (Peddada et al., 2019). In several studies, curcumin has been shown to downregulate tumor necrosis factor (TNF) -α (Li et al., 2013) and C-reactive protein (Adibian et al., 2019). Curcumin supplementation improved glycemic factors, low-density lipoprotein, very low-density lipoprotein, and triglycerides in patients with diabetes (Neerati et al., 2014). It also significantly lowered blood glucose levels (Nabavi et al., 2015) and modulated retinal disorders in diabetic rats by preventing retinal thinning, apoptosis of retinal ganglion cells and inner nuclear layer cells, and thickening the retinal capillary basement membrane (Yang et al., 2018). In obese mice, curcumin consumption significantly improved glycemic status (blood glucose, glucose tolerance, and, HbA1C) and insulin sensitivity (Weisberg et al., 2008). The effectiveness of curcumin on diabetes has been discussed in several recent meta-analyses. In a way that curcumin improves blood sugar, and lipid factors, and reduce insulin resistance, it has a beneficial effect on improving and preventing the progression of diabetes (Altobelli et al., 2021; Zhang et al., 2021; Poolsup et al., 2019).

 Proposed effect of curcumin in type I diabetes mellitus
Minia Journal of Medical Research | August 2023
People of all ages may develop diabetes mellitus, a chronic condition caused by insufficient insulin production and activity. The damaging effect of STZ on the pancreatic beta cells resulted in T1DM and protective effect of curcumin on beta cells that was evaluated by assessment of glucose and insulin, in the diabetic rats ’serum.

Proteomic analysis of ITPR2 as a new therapeutic target for curcumin protection against AFB1-induced pyroptosis
Ecotoxicology and Environmental Safety | July 2023
Curcumin exhibits excellent anti-inflammatory, and anti-cancer properties with few side effects. Curcumin has anti-oxidant, anti-inflammatory and anti-cancer properties. (Jin et al., 2020, Muhammad et al., 2018a). Modern research has discovered some unknown properties of curcumin, including anti-mutagenic, anti-cardiovascular disease and anti-microbial activities (Mahjoob and Stochaj, 2021, Mahmood et al., 2015). Curcumin has fewer side effects and plays an important role in the prevention and treatment of various diseases. Research shows that curcumin alleviates AFB1-induced liver injury by regulating Nrf2 pathway and NLPR3 inflammasome (Wang et al., 2022). Our team found curcumin can inhibit inflammatory response and oxidative stress through up-regulating the expression of Nrf2 and GST, changing long non coding RNA expression profiles, and inhibiting TLR4/RIPK pathway to protect the broilers liver injury induced by AFB1 (Li et al., 2021, Li et al., 2022, Muhammad et al., 2018b, Wang et al., 2018). In this study, we established an 8-week model of curcumin alleviating AFB1 induced liver injury in mice. Curcumin supplementation showed effective protection against AFB1-induced liver injury. This is consistent with earlier finding (Wang et al., 2022).

Antiviral Mechanisms of Curcumin and Its Derivatives in Prevention and Treatment of COVID-19: A Review
Advances in Experimental Medicine and Biology | July 2023
Curcumin, as a food nutraceutical with anti-inflammatory and antioxidant effects, is now under consideration for the prevention and treatment of COVID-19. Curcumin has been demonstrated to retard the entrance of SARS-CoV-2 into cells, interfere with its proliferation inside cells, and curb the hyperinflammatory state caused by the virus by modulating immune system regulators, minimizing the cytokine storm effect, and modulating the renin-angiotensin system.

Curcumin targets miR-134-5p to suppress the progression of colorectal cancer through regulating the CDCA3/CDK1 pathway
Naunyn-Schmiedeberg's Archives of Pharmacology | July 2023
Curcumin treatment repressed cell growth and invasion, and induced cell apoptosis in HCT-116 and SW620 cells. Curcumin elevated miR-134-5p expression and restrained CDCA3 expression in HCT-116 and SW620 cells. MiR-134-5p inhibitor or CDCA3 overexpression could restore the effects of curcumin on cell growth, apoptosis, and invasion in HCT-116 and SW620 cells. MiR-134-5p targeted CDCA3, and CDCA3 could rescue the repressive effects of miR-134-5p on the progression of colorectal cancer. Moreover, CDCA3 interacted with CDK1, and CDK1 overexpression blocked the suppressive effects of CDCA3 downregulation on the development of colorectal cancer. In addition, curcumin treatment repressed tumor growth in colorectal cancer via increasing miR-134-5p and downregulating CDCA3 and CDK1 expression in vivo. Our findings provided the evidence that curcumin upregulated miR-134-5p to inhibit the progression of colorectal cancer by regulating CDCA3/CDK1 pathway.

Turmeric Could Aid in Recovery, Study Suggests. New research highlights the anti-inflammatory benefits of the spice
Runner's World | July 2023
Dave Clayton, Ph.D., senior lecturer in nutrition and exercise physiology at Nottingham Trent University in the U.K. told Runner’s World that curcumin is a polyphenol compound with antioxidant and anti-inflammatory properties and has been shown to down-regulate various inflammatory processes. “The reduction we saw at about 64 hours post-match likely reflects a reduction in systematic inflammation, indicating that turmeric supplementation has attenuated exercise-induced inflammation,” he said. “Previous studies have also found that curcumin has reduced delayed onset muscle soreness after exercise, and we also saw that subjective muscle soreness was reduced with turmeric supplementation.”

Curcumin protects against the age-related hearing loss by attenuating apoptosis and senescence via activating Nrf2 signaling in cochlear hair cells
Biochemical Pharmacology | July 2023
Curcumin is a bioactive compound of Curcuma longa with antioxidant properties. Curcumin, extracted from the plant Curcuma longa, is a chemical monomer that can cross the blood–brain barrier to treat diseases. Curcumin has been shown to exhibit antioxidant, anti-inflammatory, anticancer, antifungal, and antiviral activities, and thus has the potential therapeutic effects on various malignant diseases and chronic illnesses. In addition, curcumin has a protective effect on degenerative diseases such as cardiomyocyte senescence, Alzheimer's disease, and lumbar radiculopathy. In an animal model of noise-induced hearing loss, curcumin prevented apoptotic index within the cochlear supporting tissues and lateral wall. We found that treatment with curcumin could attenuate progressive hearing loss in C57BL/6J mice. The above results indicate that it is of great significance to further develop curcumin as a potential agent against age-related hearing loss.

Does Curcumin Boost Testosterone Levels?
RealMuscle.co.uk | July 2023
Curcumin, the main active component in turmeric powder, was found to significantly increase the testosterone levels in male rats even when given in moderate doses. This was reported by scientists at Redeemer's University in Nigeria. The researchers investigated how gallic acid and curcumin affected the testicles of rats. Astonishingly, the curcumin group had testosterone levels that were 257% higher than the control group, and the group that received both compounds had testosterone levels that were 184% higher. According to this study, curcumin increased testosterone production and protected against the negative effects of gallic acid. The increase in testosterone levels was attributed to an increase in the activity of enzymes like 3-beta-HSD and 17-beta-HSD in the testicles. These enzymes play a crucial role in producing testosterone. The researchers concluded that curcumin could potentially be used as an alternative medication to treat male fertility issues. Curcumin also has potential to increase testosterone production.

Evaluation of Curcumin-Piperine Supplementation in COVID-19 Patients Admitted to the Intensive Care: A Double-Blind, Randomized Controlled Trial
Advances in Experimental Medicine and Biology | July 2023
Curcumin is a traditional remedy for diseases associated with hyper-inflammatory responses and immune system impairment. Piperine, a bioactive compound in black pepper, has the potential to enhance curcumin bioavailability. This study aims to examine the effect of the curcumin-piperine co-supplementation in patients infected with SARS-CoV-2 and admitted to the intensive care unit (ICU). After 1 week of the intervention, serum aspartate aminotransferase (AST) (p = 0.02) and C-reactive protein (CRP) (p = 0.03) were significantly decreased, and hemoglobin was increased (p = 0.03) in the curcumin-piperine compared to the placebo group. The study results showed that short-term curcumin-piperine supplementation significantly decreased CRP, AST, and increased hemoglobin in COVID-19 patients admitted to the ICU. Based on these promising findings, curcumin appears to be a complementary treatment option for COVID-19 patients.

Meta-study confirms positive effects of curcumin supplementation in rheumatoid arthritis
ergo-log.com | June 2023
Rheumatic patients respond well to supplementation with curcumin. According to a Chinese meta-study, curcumin reduces the inflammatory reactions that play a central role in rheumatism. As a result, patients suffer less from painful, tender and swollen joints. Curcumin supplementation reduced pain and the number of times the subjects experienced tender or swollen joints. The effect of curcumin was not only subjective in nature, but also demonstrable in medical analyses. For example, curcumin supplementation reduced the concentration of rheumatoid factors in the blood. Serious side effects did not occur.

 Role of Turmeric and Curcumin in Prevention and Treatment of Chronic Diseases: Lessons Learned from Clinical Trials
ACS Pharmacology & Translational Science | June 2023
Turmeric (Curcuma longa) has been used for thousands of years for the prevention and treatment of various chronic diseases. Curcumin is just one of >200 ingredients in turmeric. Almost 7000 scientific papers on turmeric and almost 20,000 on curcumin have been published in PubMed. A total of 148 references were found to be relevant for the key term "turmeric and clinical trials", of which 70 were common in both PubMed and Scopus, 44 were unique to PubMed, and 34 were unique to Scopus. Similarly, for the search term "curcumin and clinical trials", 440 references were found to be relevant, of which 70 were unique to PubMed, 110 were unique to Scopus, and 260 were common to both databases. These studies show that the golden spice has enormous health and medicinal benefits for humans.

 Role of the Dietary Phytochemical Curcumin in Targeting Cancer Cell Signalling Pathways
Plants | June 2023
Curcumin exhibits numerous biological effects, including anti-inflammatory, cardioprotective, antidiabetic, and anti-aging activities. It has also been extensively studied for its role as a cancer chemopreventive and anticancer agent. Curcumin has various health benefits, including anti-inflammatory, anti-allergic, antioxidant, and anticancer properties. The potential therapeutic effects of curcumin on cancer continue to draw great interest from the scientific community. The activity of curcumin on different types of cancer, including breast cancer, chronic myeloid leukaemia, head and neck squamous cell carcinoma, colorectal cancer, prostate cancer, intestinal adenomas, and cervical cancer, has been demonstrated in numerous in vitro, in vivo and clinical studies. This effect is mediated via various pathways, including PI3K/Akt, JAK/STAT, MAPK, Wnt/β-catenin, p53, NF-κB, and apoptosis-related cell signalling. Curcumin has so far shown a promising role in cancer chemoprevention and chemotherapy.

Effect of Curcumin Consumption on Inflammation and Oxidative Stress in Patients on Hemodialysis: A Literature Review
Nutrients | June 2023
Regular curcumin consumption has been shown to reduce inflammation and oxidative stress in subjects with chronic pathologies, suggesting that the daily intake of curcumin may alleviate these conditions in HD patients. Curcumin is the main active constituent of turmeric, and it is characterized by containing phenolic groups which confer antioxidant and anti-inflammatory effects. Curcumin supplementation in CKD patients on HD reduces the expression of inflammatory markers such as NF-κB, C-reactive protein and tumor necrosis factor-alpha (TNF-α).  One of the most promising bioactive compounds is curcumin, a major polyphenol in turmeric that has been successfully evaluated in the treatment of several chronic pathologies, including CKD. Several mechanisms of action associated with the antioxidant role of curcumin have been proposed as responsible for its anti-inflammatory activity. This has been evidenced in preclinical and clinical studies where regular intake of variable doses of curcumin has been effective in controlling oxidative and inflammatory parameters. Oral administration of free curcumin together with adjuvants that decrease its hepatic metabolism, such as piperine, has increased its bioavailability in both rats and humans. This literature review analyzed the available preclinical and clinical studies evaluating the antioxidant and anti-inflammatory effects of curcumin and its association with CKD. The background information gathered leads to the conclusion that curcumin consumption can be successfully integrated as a dietary therapeutic adjuvant in HD patients.

Curcumin suppressed the proliferation and apoptosis of HPV-positive cervical cancer cells
Phytotherapy Research | June 2023
Curcumin, the active ingredient of the turmeric plant, has been gaining attention over the past two decades as an antioxidant, anti-inflammatory, and anticancer agent. In the present study, the HPV-positive cervical cancer cells HeLa and CaSki were treated with curcumin, and the results showed that curcumin has a dose-dependent and time-dependent inhibitory effect on cell viability. Furthermore, the influence of different concentrations of curcumin on the mitochondrial membrane potential was evaluated through JC-1 staining and found to dramatically decrease the membrane potential in treated HeLa and CaSki cells, suggesting the critical role of the mitochondrial pathway in their apoptosis-inducing effect. This study also demonstrated the wound-healing potential of curcumin, and the results of transwell assays showed that curcumin treatment inhibited HeLa and CaSki cell invasion and migration in a dose-dependent manner compared with the control treatment. Curcumin also downregulated the expression of Bcl-2, N-cadherin, and Vimentin and upregulated the expression of Bax, C-caspase-3, and E-cadherin in both cell lines. Further research showed that curcumin also selectively inhibited the expression of the viral oncoproteins E6 and E7, as demonstrated by western blot analysis; moreover, the downregulation of E6 was more significant than that of E7. In summary, our research shows that curcumin regulates the apoptosis, migration, and invasion of cervical cancer cells, and the mechanism may be related to its ability to downregulate E6. This study provides a foundation for future research on the prevention and treatment of cervical cancer.

Curcumin activates a ROS/KEAP1/NRF2/miR-34a/b/c cascade to suppress colorectal cancer metastasis
Cell Death & Differentiation | June 2023
Curcumin has potential as a preventive and therapeutic agent for colorectal cancer, as it suppresses many hallmarks of cancer cells and exhibited promising effects in preclinical and clinical studies. For example, the addition of daily oral curcumin to FOLFOX chemotherapy significantly prolonged the progression-free survival and overall survival of patients with metastatic colorectal cancer. Moreover, curcumin showed improved erytrocyte sedimentation rate and C-reactive protein/CRP serum levels of in stage 3 colorectal cancer patients and improved their quality of life. Daily oral curcumin given to patients with advanced colorectal cancer refractory to standard chemotherapy, resulted in stable disease in 5 of 15 individuals within 4 months of follow-up evaluation. When curcumin was given in combination with mesalamine it resulted in remissions of patients with ulcerative colitis. Furthermore, in familial adenomatous polyposis/FAP patients a combination of curcumin and quercetin reduced the number and size of ileal and rectal adenomas without appreciable toxicity. The addition of curcumin to cancer therapy is of great interest, since a phase I clinical study showed that the addition of curcumin to FOLFOX treatment is safe and tolerable in patients with metastatic colorectal cancer at doses up to 2 grams daily. Moreover, oral consumption of up to 3600 mg curcumin leads to curcumin concentrations in human colorectal mucosa which are in the range of the concentration used in this study.

Curcumin inhibits proliferation of hepatocellular carcinoma cells by blocking PTPN1 and PTPN11 expression
Oncology Letters | June 2023
Curcumin was demonstrated to inhibit the growth of hepatocellular carcinoma cells tumors in mice. Immunohistochemistry results demonstrated that the protein expression levels of PTPN1 and PTPN11 in the curcumin group were significantly lower compared with those in the control group. In conclusion, these results demonstrated that curcumin inhibits the proliferation of HCC cells by inhibiting the expression of PTPN1 and PTPN11.

Pharmacological Mechanisms and Clinical Applications of Curcumin: Update
Aging and Disease | June 2023
Curcumin, a well-known hydrophobic polyphenol extracted from the rhizomes of turmeric (Curcuma longa L.), has attracted great interest in the last ten years due to its multiple pharmacological activities. A growing body of evidence has manifested that curcumin has extensive pharmacological activities including anti-inflammatory, anti-oxygenation, lipid regulation, antiviral, and anticancer with hypotoxicity and minor adverse reactions. By reviewing the latest research progress of curcumin, we believe that curcumin has a broad clinical application prospect for its wide range of pharmacological activities with few side effects.

Effect of curcumin on rheumatoid arthritis: a systematic review and meta-analysis
Frontiers in Immunology | June 2023
Curcumin is beneficial for rheumatoid arthritis treatment. Inflammation levels and clinical symptoms in patients with rheumatoid arthritis can be improved by curcumin supplementation. Large sample randomized controlled trials on the effects of curcumin on patients with rheumatoid arthritis are needed in the future. Curcumin is the most important chemical component of turmeric, which can exert antioxidant, anti-inflammatory, anti-angiogenic and anti-tumor pharmacological effects without significant adverse effects.  Previous studies have shown that curcumin and curcuminoids in turmeric could provide good protection against many chronic diseases in the body by inhibiting inflammatory responses, lowering blood lipids, and improving blood sugar. Curcumin in turmeric can effectively inhibit inflammatory reactions and reduce symptoms such as pain and swelling. In recent years, it was found that curcumin could alleviate some symptoms in some autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease. The researchers have conducted numerous studies to evaluate the pharmacological effects and clinical applications of turmeric and curcumin on rheumatoid arthritis treatment. Curcumin, a pure natural compound derived from the roots of turmeric, is one of the most active components of polyphenolic curcuminoids. Curcumin compound has been found to exert anticancer effects on a variety of molecular mechanisms through Nrf2 regulation. Curcumin is effectively used for obesity therapy because it is a lipophilic molecule that can rapidly penetrate cell membranes, and may be associated with lipid metabolism, gut microbiota, and anti-inflammatory potential. Curcumin is also known as “seasoning of life” by its well-known antibacterial, anti-inflammatory, antioxidant, antitumor, antifungal and pro-apoptotic effects. Curcumin has been shown to improve symptoms and delay disease cycles in rheumatoid arthritis patients.  The multiple double bonds in curcumin endow it with trapping free radical electrons, antioxidant activity and anti-inflammatory effects. Curcumin is beneficial for rheumatoid arthritis treatment. Inflammation levels and clinical symptoms in patients with rheumatoid arthritis can be improved by curcumin supplementation.

Curcumin inhibits colon cancer malignant progression and promotes T cell killing by regulating miR-206 expression
Clinical Anatomy | June 2023
Curcumin, as a traditional Chinese medicine extract with anti-tumor and anti-inflammatory effects, can affect the development of diverse human diseases including cancer. Curcumin treatment restrained proliferation and accelerated apoptosis of colon cancer cells. It elevated miR-206 expression, which in turn affected colon cancer cell function. miR-206 enhanced colon cancer cell apoptosis and inhibited PD-L1 expression; thus, curcumin enhanced the killing effect of T cells on tumor cells by suppressing PD-L1 through inhibiting the JAK/STAT3 pathway. Patients with high expression of miR-206 had better survival rates than those with low expression. Curcumin can regulate miR-206 expression and inhibit the malignant behavior of colon cancer cells and enhance T cell killing through the JAK/STAT3 pathway.

Turmeric supplementation improves markers of recovery in elite male footballers: a pilot study
Frontiers in Nutrition | June 2023
Curcumin, a natural polyphenol found in high concentrations in turmeric, has anti-inflammatory, antioxidant, and analgesic properties, making it a candidate to accelerate post-exercise recovery. Laboratory-based studies of cycling, running and eccentric loading protocols (e.g., downhill running, eccentric resistance exercises), have shown that curcumin supplementation before and after an exercise period can reduce subjective soreness, attenuate haematological inflammatory markers, and improve subsequent exercise performance. However, there is an absence of applied studies in elite cohorts, likely due, in part, to challenges associated with conducting research in elite cohorts. One study, in elite rugby players, found that curcumin attenuated muscle damage and limited loss of muscle function after a muscle damaging protocol, while one other study in youth team male footballers found that curcumin attenuated DOMS and loss of muscle function after match-play.  The supplement also contained piperine, an adjuvant that can greatly improve bioavailability of curcumin. High doses of curcumin (up to 12 g per day) are pharmacologically safe and well tolerated in humans. Piperine slows the metabolism of curcumin by inhibiting hepatic and intestinal glucuronidation. Previous studies have shown that administering curcumin with piperine can increase serum concentrations of curcumin by up to 2000%, indicating that glucuronidation inhibition may be the major mechanism of increasing curcumin bioavailability. As such, the formulation of the supplement administered in the current study, which contained 35 g of raw turmeric root, (estimated to contain 1,400 mg of curcumin) and 10 mg of piperine, may have helped to increase serum concentrations of curcumin such that it could exert its biological action, whilst the mode of administration may have encouraged greater adherence.

Cardioprotective effect of curcumin on myocardial ischemia/reperfusion injury: a meta-analysis of preclinical animal studies
Frontiers in Pharmacology | June 2023
A total of 38 studies were included in this meta-analysis, and the results suggested that curcumin significantly reduced the myocardial IS, improved cardiac function parameters, downregulated serum myocardial enzyme, improved antioxidant ability, decreased serum inflammatory cytokines, and myocardial apoptosis index. In conclusion, our results demonstrated a significant cardioprotective effect of curcumin at multiple levels in animal models of myocardial I/R injury. The results of this study showed that curcumin significantly reduces myocardial IS, improves cardiac function, downregulates myocardial enzyme levels, inhibits oxidative stress, decreased serum inflammatory cytokines, and myocardial apoptosis index to play a cardioprotective role in animal models of myocardial I/R injury. This meta-analysis suggests that curcumin has excellent potential for the treatment of myocardial I/R injury in animal models. Curcumin treatment significantly improved myocardial infarction size standard mean difference (SMD) = −5.65; 95% confidence interval. In addition, curcumin treatment improved cardiac function, myocardial injury enzymes, and oxidative stress levels in animal models of myocardial I/R injury. The results showed that curcumin treatment downregulated serum inflammatory cytokine levels and myocardial apoptosis index. Conclusion: This meta-analysis suggests that curcumin has excellent potential for the treatment of myocardial I/R injury in animal models. Curcumin was proven to be well tolerated at high oral doses (12 g/d) and was generally considered to be safe (Lao et al., 2006; Gupta et al., 2013; Prasad et al., 2014). Recent studies have shown that curcumin protects cardiomyocytes from myocardial I/R injury through multiple and diverse mechanisms (Wang et al., 2018a; Mokhtari-Zaer et al., 2018; Wu et al., 2021a; Pawar et al., 2022). Curcumin has been shown to improve cardiac function after myocardial I/R injury by reducing extracellular matrix degradation and inhibiting collagen synthesis via the TGFβ/Smad signaling pathway (Wang et al., 2012). In addition, curcumin attenuates oxidative damage and inhibits cardiomyocyte apoptosis by activating the JAK2/STAT3 signaling pathway, thereby ameliorating myocardial I/R injury (Liu et al., 2017a).

Curcumin as a therapeutic agent in cancer therapy: Focusing on its modulatory effects on circular RNAs
Phytotherapy Research | June 2023
Curcumin, a natural polyphenol compound, has been identified as an effective therapeutic agent against cancer that exerts its anti-tumor activities by up/downregulating signaling mediators and modulating various cellular processes, including angiogenesis, autophagy, apoptosis, metastasis, and epithelial–mesenchymal transition (EMT). Since almost 98% of genomic transcriptional production is noncoding RNAs in humans, there is evidence that curcumin exerts therapeutic effects through the alterations of noncoding RNAs in various types of cancers. It has been shown that curcumin modulated various circRNAs. In this article, we reviewed the pharmacokinetics of curcumin, its anti-cancer activities, as well as the biology and structure of circRNAs. Our main focus was on how curcumin exerts anti-cancer functions by modulating circRNAs and their target mRNAs and pathways.

Curcumin activates a ROS/KEAP1/NRF2/miR-34a/b/c cascade to suppress colorectal cancer metastasis
Cell Death & Differentiation | June 2023
Curcumin is a polyphenol derived from the rhizome of the turmeric plant (Curcuma longa) and has been a popular food additive in Eastern cuisine. In addition, it has been used for centuries in traditional Chinese and ayurvedic medicine. Notably, curcumin has potential as a preventive and therapeutic agent for CRC, as it suppresses many hallmarks of cancer cells and exhibited promising effects in preclinical and clinical studies. For example, the addition of daily oral curcumin to FOLFOX chemotherapy (folic acid/5-fluorouracil/oxaliplatin) significantly prolonged the progression-free survival and overall survival) of patients with metastatic CRC. Moreover, curcumin showed improved erytrocyte sedimentation rate and C-reactive protein/CRP serum levels of in stage 3 CRC patients and improved their quality of life. Daily oral curcumin given to patients with advanced colorectal cancer refractory to standard chemotherapy, resulted in stable disease in 5 of 15 individuals within 4 months of follow-up evaluation. When curcumin was given in combination with mesalamine it resulted in remissions of patients with ulcerative colitis/UC. Furthermore, in familial adenomatous polyposis/FAP patients a combination of curcumin and quercetin reduced the number and size of ileal and rectal adenomas without appreciable toxicity. As the clinical studies only included small numbers of patients, larger, targeted and prospective clinical trials are required to establish curcumin in clinical practice. Curcumin was shown to affect the expression of non-coding RNAs in CRC cells. Also miR-34a, a p53-inducible microRNA with tumor-suppressive capacities, was induced by exposure to curcumin. our results provide a plausible mechanism for the effects that have been ascribed to curcumin in the prevention and therapy of colorectal cancer and other malignancies. The members of the miR-34 family are frequently silenced in colorectal tumors by DNA methylation. There is evidence that curcumin can reactivate CpG methylated genes. Therefore, CpG-methylation of miR-34a/b/c is presumably not an obstacle for treatment of CRC with curcumin. Originally this study was intended to determine the mode of action of curcumin during tumor prevention. In that scenario, miR-34a/b/c should not be silenced by CpG-methylation. We showed that the anti-tumor effects of curcumin are less pronounced in miR-34-deficient cells. Therefore, it will be important to investigate the in vivo effects of curcumin on CRC treatment and prevention with respect to miR-34 expression in the future. For example, future experiments should include the treatment of wt and miR-34 knockout mouse models of CRC with curcumin and/or chemotherapy. Howells et al. showed in a phase IIa clinical study that the addition of curcumin to FOLFOX treatment significantly improved the progression free and overall survival. The addition of curcumin to cancer therapy is of great interest, since a phase I clinical study showed that the addition of curcumin to FOLFOX treatment is safe and tolerable in patients with metastatic CRC at doses up to 2 grams daily. Moreover, oral consumption of up to 3600 mg curcumin leads to curcumin concentrations in human colorectal mucosa which are in the range of the concentration used in this study. In the future, the findings presented here may be exploited for the development of therapeutic approaches that aim at restoring the tumor suppressive function of the p53/miR-34 pathway.

Curcumin Enhances the Abscopal Effect in Mice with Colorectal Cancer by Acting as an Immunomodulator
Pharmaceutics | June 2023
Curcumin has been shown to exert anti-tumor and immunomodulatory properties in several studies. Curcumin suppresses tumor growth by generating reactive oxygen species (ROS) and inducing apoptosis. Curcumin triggers apoptosis in HCT-116 cells by inhibiting NF-κB activation and downstream pathways. Curcumin has been found to cause more DNA damage and cell deaths in Panc-1 and MiaPaCa-2 cells when combined with RT. Additionally, curcumin exerts immunomodulation potential and slows tumor progression. For instance, curcumin augments tumor inhibition by enhancing the proliferation and activation of T cells. Curcumin can also suppress tumor growth by repressing the generation and activity of TGF-β-induced regulatory T cells. We chose curcumin for combination treatment due to its anti-tumor and immunomodulatory abilities. Curcumin has been found to repress the expression of NF-κB and PD-L1. Liao et al. reported that curcumin suppresses PD-L1 levels and improves the tumor immune microenvironment in tongue squamous cell carcinoma. The results showed that combining curcumin with RT resulted in the most significant tumor inhibition in primary and secondary tumors. This finding suggests that curcumin has the potential to enhance the abscopal effect and improve treatment outcomes. Curcumin has been found to improve the effectiveness of different treatments in various cancers. For example, Hussain et al. summarized that curcumin can augment the efficacy of cisplatin and reduce treatment resistance by increasing ROS generation and triggering apoptosis cascades in multiple cancer types. A combination of curcumin and doxorubicin has also been shown to help tumor control by disturbing cell cycle progression and the balance between apoptosis and anti-apoptosis in head and neck cancer. Curcumin has also been combined with FLLFOX chemotherapy for treating patients with metastatic colorectal cancer, resulting in significant improvement in overall and progression-free survival. However, further research is needed to fully elucidate the mechanisms underlying the beneficial effects of curcumin in cancer treatment. Curcumin enhances radiosensitivity by regulating epigenetics, DNA damage repair, and apoptosis in various cancers, including nasopharyngeal cancer, bladder cancer, and glioblastoma. Curcumin can also enhance radiotherapy through anti-inflammatory mechanisms. Additionally, curcumin may enhance radiotherapy through anti-inflammatory mechanisms. Our findings demonstrate that curcumin enhances the abscopal effect in a bilateral CT26 tumor-bearing mouse model by suppressing NF-κB and downstream proteins, elevating IL-1β and IL-6, and modulating the overall tumor immune microenvironment, thereby enhancing tumor suppression. We also validated that curcumin enhances RT outcomes and boosts the anti-tumoral immune responses in bilateral CT26-luc tumor-bearing mice by performing a biodistribution study of 111In-DOTA-anti-OX40 mAb, ELISA assay, and Western blot. These results suggest that curcumin acts as an immunomodulator to improve RT outcomes.

Effect of Curcumin and Coenzyme Q10 Alone and in Combination on Learning and Memory in an Animal Model of Alzheimer’s Disease
Biomedicines | June 2023
Curcumin has a wide range of biological and pharmacological effects, including those that are antibacterial, anti-inflammatory, antioxidant, anti-tumour, anti-protozoa, and anti-HIV. This has been demonstrated by modern medicine. According to the Joint Nations and World Health Organization Expert Committee on Food Additives (JECFA), curcumin is regarded as a safe chemical and is hence appropriate for everyday dietary usage. Curcumin is a viable drug candidate for the treatment of complicated disorders such as Alzheimer’s disease and its related cognitive loss because of its pleiotropic effects and good safety profile. Curcumin has demonstrated a dose–response relationship, with a higher dose (200 mg/kg b.w. p.o.) being more effective than a lower dose (100 mg/kg b.w. p.o.). We may infer from our results that curcumin at higher doses and its combination with coenzyme Q10 have a significant impact on cognitive impairment in animal models of Alzheimer’s disease and can be utilised alone or as an add-on therapy for the condition. The bioavailability of curcumin was significantly increased by 2000% when 20 mg of piperine, which is extracted from black pepper, was also taken as a supplement.  Curcumin has a learning and memory enhancement effect and a higher dose is comparatively more effective than a lower dose  and it has shown a dose–response effect. The effects of the combination of curcumin and coenzyme Q10 on learning and memory were significant and greater than when both drugs were given alone and were comparable to Memantine. The results of the present study are encouraging and may reveal the importance of curcumin and coenzyme Q10 herbal drugs and nutrients in impaired cognition states. As a result, curcumin, coenzyme Q10, and their combination, which has demonstrated the greatest benefit, may be effective in the management of learning- and memory-impaired states as an alternative, supplemental, or even preventive medication. These medications, alone or in combination, can be taken by patients of any age for a longer period of time without experiencing any negative side effects.

Journal of Pharmaceutical Research Curcumin from turmeric is an extremely efficient agent in increasing cholesterol uptake by the liver cells
Journal of Pharmaceutical Research | May 2023
Curcuma longa decreased total cholesterol, TG, LDL cholesterol 16.10, 20.01, and 17.59 mg/dl respectively. Curcuma longa, Fenugreek leaves and Lemon are mild to moderately effective hypolipidemic herbs to lower total plasma cholesterol, triglycerides, and LDL cholesterol. Curcumin reduces both the oxidation and circulation of oxidized levels of LDL cholesterol which leads to reduction in the occurrence or treatment of already present atherosclerosis in the subjects. Research has revealed that curcumin from turmeric is an extremely efficient agent in increasing cholesterol uptake by the liver cells. Several independent studies have shown that curcumin increases the expression of cholesterol and lipoprotein receptors on the liver cells. Curcumin also in- creases cholesterol and bile acids excretion in feces. Additionally, curcumin also increases the amount of ABC (ATP-binding cassette) transporters. Phenolics in Curcuma Longa have potential health benefits mainly due to their antioxidant properties such as reactive oxygen species (ROS) scavenging and inhibition, electrophile scavenging and metal chelation.

 Curcumin Attenuates Delayed-Onset Muscle Soreness and Muscle Function Deficits Following a Soccer Match in Male Professional Soccer Players
International Journal of Sports Physiology and Performance | May 2023
Curcumin attenuated deficits in CMJ (P ≤ .004) and RSI (P ≤ .001) and reduced Delayed-Onset Muscle Soreness (P ≤ .004) at all postmatch time points (except 60 h post for RSI). The greatest difference between control and curcumin was 12 hours post for CMJ (P < .001, 1.91 [4.40] cm, 95% CI, 1.25 to 2.57, g = 0.36) and RSI (P = .003, 0.40 [0.41] AU, 95% CI, 0.17 to 0.63, g = 0.90) and 36 hours post for Delayed-Onset Muscle Soreness (P < .001, 47 [23] mm, 95% CI, −67 to −27, g = 2.12). Conclusions: Curcumin intake <36 hours after a soccer match attenuated Delayed-Onset Muscle Soreness and muscle function deficits, suggesting that curcumin may aid recovery in professional male soccer players.

The effects of curcumin on astrocytes in common neurodegenerative conditions
Mini-Reviews in Medicinal Chemistry | May 2023
Curcumin, with multiple special properties, has been effectively prescribed to manage various diseases. It has hepato-protective, anti-carcinogenic, cardio-protective, thrombo-suppressive, anti-inflammatory, chemo-therapeutic, anti-arthritic, chemo-preventive, and anti-oxidant activities. In the current review, the effects of curcumin on astrocytes in common neurodegenerative conditions, such as Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer's disease, and Parkinson's disease, are discussed. Hence, it can be concluded that astrocytes play a critical role in neurodegenerative diseases, and curcumin is able to directly modulate astrocyte activity in neurodegenerative diseases.

Curcumin reduces paclitaxel resistance in ovarian carcinoma cells by upregulating SNIP1 and inhibiting NFκB activity
Biochemical Pharmacology | May 2023
Curcumin inhibits NFκB activity by modulating the EGR1/SNIP1 axis to attenuate p65 acetylation and protein stability in Txr cells. These findings provide a new mechanism to account for the effects of curcumin in inducing apoptosis and reducing paclitaxel resistance in ovarian cancer cells. Curcumin has been described as having unique anticancer activity, including inducing apoptosis and inhibiting proliferation and invasion of tumors by suppressing a variety of cellular signaling pathways. It was reported that curcumin induced cell apoptosis and increased paclitaxel sensitivity by interfering with NFκB, p53, and caspase-3 signaling. Moreover, curcumin’s anticancer properties have primarily been attributed to blocking the transcriptional factor NFκB activity. Curcumin, a dietary phytochemical obtained from the dried rhizomes of Curcuma longa (turmeric), has been used as a food additive and as a form of traditional herbal medicine. In combination with 5-fluorouracil (5-FU), docetaxel, or paclitaxel, curcumin significantly enhanced chemotherapy sensitivity and produced significant health benefits]. The anticancer properties of curcumin have been primarily attributed to its ability to block the transcriptional factor NFκB, which is a master regulator of inflammation, cell proliferation, apoptosis, and drug resistance. Therefore, curcumin may be used against paclitaxel-resistant cancer cells induced by TLR4 signaling, which activates NFκB and upregulates downstream taxol-resistance genes. In addition, curcumin has been reported to inhibit NFκB activity.

Effects of Curcumin on Axon Growth and Myelin Sheath Formation in an In Vitro Model
Neurochemical Research | May 2023
Although the beneficial effects of curcumin, extracted from rhizomes of the ginger family genus Curcuma, on the repair and regeneration of nerves have been evaluated in vitro, there are few studies concerning its effects on axon myelination. We found a significant increase in expression of all six proteins following curcumin treatment, with a corresponding increase in the levels of MBP, MPZ, Krox-20, and Oct-6 mRNA. The results suggested that curcumin can promote the growth of axons by upregulating the expression of GAP-43 and MAP-2, stimulate synthesis and secretion of myelin-related proteins, and facilitate formation of the myelin sheath in axons by upregulating the expression of Krox-20 and Oct-6. Therefore, curcumin could be widely applied in future strategies for the treatment of nerve injuries.

Curcumin Improves Diabetic Cardiomyopathy by Inhibiting Pyroptosis through AKT/Nrf2/ARE Pathway Mediators of Inflammation
Mediators of Inflammation | May 2023
Curcumin is a natural antioxidant that protects cells from inflammatory damage and has therapeutic effects in diseases such as myocardial, kidney, and liver injuries. Li et al.’s report found that curcumin can improve mercuric chloride-induced liver injury through the Nrf2/ARE pathway. Zhao et al.’s study found that curcumin inhibited autophagic death caused by HgCl2 through the PI3K/AKT/Nrf2 pathway, thereby improving spleen damage. Therefore, curcumin is a natural agonist of Nrf2, which provides a good pharmacological basis for the treatment of diabetic cardiomyopathy. Current research has found that curcumin has a good therapeutic effect on the complications of diabetes. Curcumin can inhibit the NF-κB/p65 pathway in the nervous system of diabetic rats, increasing the activity of superoxide dismutase and reducing the level of inflammatory factors. ALTamimi found that curcumin could inhibit the PKCβ/p66shc axis and activate FOXO-3a, reversing diabetic nephropathy in rats. The present study found that curcumin can inhibit the progression of pyroptosis in diabetic cardiomyopathy, reduce the degree of myocardial fibrosis, and inhibit the decline of cardiac function by regulating the AKT/Nrf2/ARE pathway. Therefore, our findings support the therapeutic potential of curcumin and provide a new theoretical basis for the treatment of diabetic cardiomyopathy. This study found that curcumin can promote the transfer of Nrf2 into the nucleus through the AKT pathway and increase the expression of the downstream antioxidant factors HO-1 and GCLC. These effects cleared the accumulation of ROS in diabetic cardiomyocytes, alleviated mitochondrial damage, inhibited the progression of pyroptosis, and had a role in the treatment of diabetic cardiomyopathy.

Curcumin alleviated oxidation stress injury by mediating osteopontin in nephrolithiasis rats
Acta Cirúrgica Brasileira | May 2023
Curcumin could reduce the oxidative stress damage caused by EG-induced kidney stones. Curcumin (Cur) is a polyphenolic substance isolated from the turmeric rhizome. Curcumin is the main active component of turmeric, and it has various functions, including antioxidant, anti-inflammatory, antifibrosis8, antibacterial and antitumor activities, and protection from oxidative damage in the kidney. Animal models of oxidative damage to kidney tissue and kidney stones have proven that curcumin can reduce the expression of inflammation-related factors, and induce anti-inflammatory factors to inhibit the activation of the MAPK/ERK, TGF-β/Smad, and PPAR-γ pathways. In addition, curcumin could induce the antioxidant response in the kidney, and nuclear factor Nrf2 to play a regulatory role, inhibit mitochondrial dysfunction, reduce inflammation and prevent oxidative stress damage. Studies have shown that curcumin exhibits important renal protection and stone suppression effects in kidney diseases. The subcutaneous injection of curcumin could alleviate the oxidative stress damage of calcium oxalate kidney stones induced by EG within a specific dose range. Curcumin may dissolve calcium oxalate stones in the renal tubules of rats and reduce the oxidative damage of calcium oxalate stones to the kidneys. Therefore, curcumin could be used as a new drug candidate to treat kidney stones.

Anti-Allergic Effect of Dietary Polyphenols Curcumin and Epigallocatechin Gallate via Anti-Degranulation in IgE/Antigen-Stimulated Mast Cell Model: A Lipidomics Perspective
Metabolites | May 2023
Both curcumin and EGCG significantly inhibited degranulation as they suppressed the release of β-hexosaminidase, interleukin-4, and tumor necrosis factor-α from the IgE/antigen-stimulated mast cell model. Remodeling patterns (lipid response and composition) of curcumin intervention were considerably similar to those of EGCG, lipid metabolism was more potently disturbed by curcumin. Seventy-eight percent of significant differential lipids upon IgE/antigen stimulation could be regulated by curcumin/EGCG. LPC-O 22:0 was defined as a potential biomarker for its sensitivity to IgE/antigen stimulation and curcumin/EGCG intervention. The key changes in diacylglycerols, fatty acids, and bismonoacylglycerophosphates provided clues that cell signaling disturbances could be associated with curcumin/EGCG intervention. Our work supplies a novel perspective for understanding curcumin/EGCG involvement in antianaphylaxis and helps guide future attempts to use dietary polyphenols. Curcumin got approved to be “generally recognized as safe” (GRAS) by the US Food and Drug Administration (FDA). Two typical dietary polyphenols, curcumin and EGCG, were confirmed to show anti-allergic potential in the present study. Both curcumin and EGCG significantly suppressed the release of β-hexosaminidase, IL-4, and TNF-α from IgE/antigen-stimulated RBL-2H3 cells. As compared to the alteration pattern associated with IgE/antigen-stimulated degranulation (Veh vs. AG), the lipidome modulation by curcumin/EGCG could be identified (Cur vs. AG and EGCG vs. AG). Comprehensive lipidomics analysis revealed that the ability to disturb lipid metabolism was stronger with curcumin than EGCG, in accordance with the superior ability of curcumin to suppress the degranulation process. These key lipidome disturbances provide novel insights into the effects of curcumin/EGCG intervention underlying the progression of degranulation. Our findings open the possibility of preventing immediate allergic reactions via antigen-stimulated mast cells in vitro and will help guide future attempts to use dietary polyphenols.

Curcumin and whey protein concentrate binding: Thermodynamic and structural approach
Food Hydrocolloids | May 2023
Curcumin is a natural hydrophobic polyphenol (Liu, Chen, Cheng, & Selomulya, 2016), first isolated from the rhizome of turmeric (Curcuma longa), and it has a varied range of beneficial biological activities. According to recent studies, it is recognized that curcumin has the ability to enhance human health, particularly due to its antioxidant, anti-inflammatory, anticancer, antibacterial and antiviral activities. For example, it was reported that curcumin reduces cholesterol and platelet aggregation (Suresh & Srinivasan, 2010), inhibits proliferation of cancer cells (Naksuriya, van Steenbergen, Torano, Okonogi, & Hennink, 2016; Shabaninejad et al., 2020; Taebi et al., 2020) and improves digestion (Dulbecco & Savarino, 2013). In addition, the curcumin , as an antiviral and anti-inflammatory agent, might be helpful for both prevention and treatment of COVID 19 (Dhar & Bhattacharjee, 2021; Jennings & Parks, 2020). Overall, the documented anti-inflammatory and immunomodulatory effects of curcumin (Yadav, Mishra, Singh, Mehrotra, & Singh, 2005) along with the evidence on its anti-fibrotic effects (Gorabi et al., 2020) on the lung tissue make it a promising candidate for the treatment of COVID-19 (Dourado et al., 2021; Manoharan et al., 2020).

Cannabinoid compounds in combination with curcumin and piperine display an anti-tumorigenic effect against colon cancer cells
Frontiers in Pharmacology | May 2023
Evidence supported by experimental findings suggest that micronutrients such as curcumin and piperine may present a safer strategy in preventing tumorigenesis and its recurrence. Recent studies demonstrated that piperine potentiates curcumin’s inhibitory effect on tumor progression via enhancing its delivery and therapeutic activity.  It is possible to reduce colorectal cancer death rate by as much as 90% through inclusion of naturally existing bio-compounds with the anti-cancer and anti-oxidant characteristics such as curcumin. It is suggested that curcumin can selectively kill tumor cells through its multifaceted metabolic effects, that culminate in its anti-oxidant and anti-inflammatory activities (Hewlings and Kalman, 2017). Several clinical trials classify curcumin as a potential chemo-preventive and chemotherapeutic agent (Doello et al., 2018).  In exerting its anti-tumorigenic effects, curcumin blocks angiogenesis, and negatively regulates cancer cell cycle progression as well as metastatic activity. In several combinatorial therapy approaches, where a secondary active drug agent or drug candidate is co-administered with curcumin, an increase in the therapeutic benefit from curcumin has been reported in diverse cancer models (Baldi et al., 1839), (Bolat et al., 2020), (Schmidt et al., 2020). Strikingly, the second agent turns out to enhance curcumin-dependent anti-cancer activity in a synergistic fashion in certain cases. Among the numerous candidates tested so far, curcumin, piperine and certain types of cannabinoids performed promisingly well in colon carcinoma models as monotherapy agents. Piperine, a dietary polyphenol isolated from black and long peppers, distinguished with its intrinsic features, improves -not only-curcumin’s existing anti-cancer activity, but also its extremely poor bioavailability (Tang et al., 2017) (Tang et al., 2017) As a single agent, piperine alone also displays anti-mutagenic and anti-tumor activities (Chinta et al., 2015). For example, this agent can inhibit the proliferation of colon cancer cell lines via induction of a cell cycle arrest in the G1 phase, while it triggers apoptosis in prostate cancer models (Ouyang et al., 2013), (Yaffe et al., 2015).

Curcumin can improve spinal cord injury by inhibiting DNA methylation
Molecular and Cellular Biochemistry | May 2023
Curcumin is a natural polyphenol from turmeric. It has anti-inflammatory, antioxidant, and neuroprotective effects, and can mitigate the cell and tissue damage caused by spinal cord injury. This report analyzed the specific functions of DNA methylation in central nervous system diseases, especially traumatic brain injury and spinal cord injury. DNA methylation can regulate the level of gene expressions in the central nervous system. Therefore, pharmacological interventions regulating DNA methylation may be promising for spinal cord injury.

Curcumin Improves Diabetic Cardiomyopathy by Inhibiting Pyroptosis through AKT/Nrf2/ARE Pathway
Mediators of Inflammation | May 2023
Curcumin is a natural antioxidant that protects cells from inflammatory damage and has therapeutic effects in diseases such as myocardial, kidney, and liver injuries. Li et al.’s report found that curcumin can improve mercuric chloride-induced liver injury through the Nrf2/ARE pathway. Zhao et al.’s study found that curcumin inhibited autophagic death caused by HgCl2 through the PI3K/AKT/Nrf2 pathway, thereby improving spleen damage. Therefore, curcumin is a natural agonist of Nrf2, which provides a good pharmacological basis for the treatment of diabetic cardiomyopathy. Current research has found that curcumin has a good therapeutic effect on the complications of diabetes. Curcumin can inhibit the NF-κB/p65 pathway in the nervous system of diabetic rats, increasing the activity of superoxide dismutase and reducing the level of inflammatory factors. Al-Tamimi found that curcumin could inhibit the PKCβ/p66shc axis and activate FOXO-3a, reversing diabetic nephropathy in rats. The present study found that curcumin can inhibit the progression of pyroptosis in diabetic cardiomyopathy, reduce the degree of myocardial fibrosis, and inhibit the decline of cardiac function. Therefore, our findings support the therapeutic potential of curcumin and provide a new theoretical basis for the treatment of diabetic cardiomyopathy. This study found that curcumin can promote the transfer of Nrf2 into the nucleus through the AKT pathway and increase the expression of the downstream antioxidant factors HO-1 and GCLC. These effects cleared the accumulation of ROS in diabetic cardiomyocytes, alleviated mitochondrial damage, inhibited the progression of pyroptosis, and had a role in the treatment of diabetic cardiomyopathy.

The Combined Effect of Curcumin and Crocin on the Reduction of Inflammatory Responses in Arthritic Rats
Current Medicinal Chemistry | April 2023
Crocin, curcumin and crocin + curcumin administration showed effective anti-arthritic effects owing to their anti-inflammatory effects. Therefore, crocin and curcumin, either alone or in combination, can be a suitable treatment modality for rheumatoid arthritis.

The Apoptotic Activity of Curcumin Against Oral Cancer Cells Without Affecting Normal Cells in Comparison to Paclitaxel Activity
Applied Biochemistry and Biotechnology | April 2023
Curcumin and paclitaxel (PTX) have significant anti-cancer activity against normal human gingival fibroblast and tongue squamous cell carcinoma fibroblast cell lines. The results showed that curcumin (13.85 µg mL−1) and PTX (8.17 µg mL−1) significantly inhibited TSCCF cell viability, with no significant effect on normal HGF cells.  For TSCCF, the results showed the highest necrosis was achieved with curcumin (58.8%) and PTX (39%) as compared to the control (2.99%).  In conclusion, the results confirmed that curcumin is more specific to the oral cancer cells but not normal cells by inducing apoptosis in a dose- and time-dependent manner, with decreased TSCCF cell viability
.

 Curcumin Epigenetically Represses Histone Acetylation of Echinocandin B Producing Emericella rugulosa
Physiologia | April 2023
Analysis revealed suppression of the echinocandin B levels in the cells treated with curcumin. Curcumin was also found to repress the expression of different ecd genes by several folds. Taken together, we conclude that curcumin targets echinocandin B production by inhibiting histone acetylation as well as disrupting interspecies consortium communication, which eventually leads to a decrease in the echinocandin B synthesis. The curcumin treatment to E. rugulosa NRRL11440 showed severe impairment of the echinocandin B production as supported by the HPLC analysis. Curcumin treatment to E. rugulosa NRRL11440 was found to suppress the echinocandin B antifungal biosynthesis by repression of gene expression of a transcriptional factor ecdB and an NRPS-coded ecdA which shows reduced cell susceptibility against C. albicans. Curcumin may turn out to be an effective histone acetyltransferase inhibitor for limiting acetylation on the histone proteins.

Curcumin and chemokines: mechanism of action and therapeutic potential in inflammatory diseases
Inflammopharmacology | April 2023
Curcumin, the major component of the Curcuma longa rhizome, has various pharmacological actions, including anti-inflammatory, immune-regulatory, anti-oxidative, and lipid-modifying properties. Curcumin is a safe phytochemical that elicits a wide range of biological actions in the human body. It shows anti-inflammatory, antioxidant, lipid-modulating, anti-thrombotic, immunomodulatory, hepatoprotective, anti-diabetic, anti-tumor, and neuroprotective actions (Qadir et al. 2016; Bavarsad et al. 2019; Ghasemi et al. 2019; Iranshahi et al. 2009; Panahi et al. 2017b; Parsamanesh et al. 2018; Sahebkar and Henrotin 2016; Alidadi et al. 2020; Heidari et al. 2022; Vahedian-Azimi et al. 2022; Mohammed et al. 2021). In addition, curcumin influences various cells and molecular targets like growth factors, cytokines/chemokines, hormones, transcription factors, cell adhesion molecules, protein kinases, redox state enzymes, and receptors (Esatbeyoglu et al. 2012; H. Zhou et al. 2011; Mashayekhi-Sardoo et al. 2021; Mohajeri et al. 2020; Soltani et al. 2021; Ganjali et al. 2017b; Momtazi-Borojeni et al. 2018). The anti-inflammatory effects of curcumin are mediated by downregulation in the activity of cyclooxygenase-2 (COX-2), lipoxygenase (LOX), inflammasome, and inducible nitric oxide synthase (iNOS) (Goel et al. 2008b, 2008a; Hassanzadeh et al. 2020). Moreover, curcumin also inhibits IL-2, IL-6, IL-8, IL-12, TNF-α, macrophage inhibitory protein (MIP), and the production of monocyte chemoattractant protein-1 (MCP-1) pro-inflammatory cytokines and chemokines (Abe et al. 1999), as well as down-regulates mitogen-activated and janus kinases (Natarajan and Bright 2002; Siwak et al. 2005). These biological effects appear to be achieved by curcumin-mediated inhibition of NF-κB (Surh et al. 2001; Zhong et al. 2012; Lee et al. 2005; Ji et al. 2009; Zhao et al. 2014). The regulatory and anti-inflammatory effects of curcumin are well established, and it exerts its pharmacological effects through various molecular targets. In general, the biological effects of curcumin are broadly thought to be achieved by inhibition of NF-κB, although, more specifically, the actual anti-inflammatory effects of curcumin are primarily mediated by downregulation in the activity COX-2, LOX, and iNOS. Curcumin can exert its inhibitory effects on chemokines, which generally function as pro-inflammatory mediators and are responsible for the recruitment of immune cells to sites of inflammation. As it relates to the neuroprotective effects provided to neuroglia and neurons, curcumin modulates the expression of different chemokines and reduces degeneration, injuries, and deficits associated with these cells' neuroinflammation. Moreover, the inhibitory effect of curcumin on hepatic, cardiovascular, pulmonary, and renal inflammatory conditions results in decreased fibrosis and other inflammation-associated histological complications. Lastly, in the case of cancer, curcumin can inhibit chemokine expression, leading to inhibition of tumor metastasis and activating specific chemokines that recruit anti-tumor immune cells to the tumor microenvironment.

Curcumin Confers Anti-Inflammatory Effects in Adults Who Recovered from COVID-19 and Were Subsequently Vaccinated: A Randomized Controlled Trial
Nutrients | April 2023
Curcumin intake confers anti-inflammatory activity and may be a promising prophylactic nutraceutical strategy for COVID-19. 4 weeks of curcumin supplementation resulted in significantly lower concentrations of proinflammatory cytokines in adults who recovered from COVID-19 infection and were subsequently vaccinated. Curcumin, a polyphenolic compound derived from the rhizomes of turmeric (Curcuma Longa), providing the spices’ yellow pigment, has been recognized for its anti-inflammatory, antioxidant, anti-viral, and immune modulating properties. Several studies have demonstrated the effect of curcumin to inhibit inflammatory signaling pathways such as nuclear factor-kappa B (NF-kB) in several cell types and disease models and reduce the induction of several proinflammatory cytokines and chemokines Given the evidence to suggest the anti-viral and anti-inflammatory activity of curcumin, the interest in this dietary compound as an adjunctive strategy for COVID-19 has risen. Importantly, curcumin has also exhibited good safety and tolerability profiles in clinical trials, even at high doses. We demonstrated that curcumin supplementation was associated with significantly lower levels of the proinflammatory cytokines IL-6 and MCP-1, which increased in the control group during the four-week trial period. These findings indicate that curcumin supplementation may help to control inflammation and support resilience.

Curcumin protects against doxorubicin induced oxidative stress by regulating the Keap1-Nrf2-ARE and autophagy signaling pathways
Psychopharmacology | April 2023
Curcumin relieves depressive-like state through the mitigation of oxidative stress and the activation of Nrf2-ARE signaling pathway. Curcumin, a yellow coloring agent extracted from curcuma longa, has pharmacological effects including antioxidant, anti-inflammatory, immunomodulatory, and neuroprotective activities (Aggarwal and Harikumar 2009; Maheshwari et al. 2006). Notably, curcumin’s antioxidative properties hold a great deal of potential for neuroprotective effect. Previous studies have reported that the main mechanism of curcumin the treatment of oxidant stress-related diseases was the activation of Nrf2 (Madiha and Haider 2019; Yang et al. 2009). Our previous study have revealed that curcumin relieves depressive-like state through the mitigation of oxidative stress and the activation of Nrf2-ARE signaling pathway (Liao et al. 2020). By activating Nrf2-ARE signaling, curcumin exerts its chemopreventive effects via the induction of antioxidant enzymes (Scapagnini et al. 2011). Soetikno et al. have also reported that curcumin alleviates oxidative stress, inflammation, and renal fibrosis in remnant kidney through the Nrf2-keap1 pathway (Soetikno et al. 2013). Scapagnini et al. have reported that curcumin strongly induces HO-1 expression and activity in different brain cells via the activation of Keap1-Nrf2-ARE signaling pathway (Scapagnini et al. 2011). Balogun et al. have also reported that curcumin exhibited its chemopreventive effect by selectively activating the Nrf2-Keap1-ARE signaling pathway (Balogun et al. 2003).Our present study has demonstrated that curcumin exhibited great potential to reverse the depressive-like behavior in DOX-treated rats. DOX-induced excessive oxidative stress causes the upregulation of autophagy, and autophagy acts as an antioxidant feedback response activated by the p62-Keap1-Nrf2 feedback loop. The possible mechanism under behavior-modulating and neuroprotective effects of curcumin is the activation of p62-Keap1-Nrf2 signaling pathway.

 Impact of Curcumin Supplementation on Radiation Dermatitis Severity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Asian Pacific Journal of Cancer Prevention | April 2023
Curcumin has recently attracted more attention for managing the side effects of breast cancer treatments. Based on the results of the present study, curcumin has significant effects in reducing the severity of radiation dermatitis in breast cancer patients receiving radiotherapy. Amongst the wide range of medical herbs, curcumin is a component of the turmeric plant and a potent antioxidant and anti-inflammatory agent used to treat skin ailments, such as scabies, acne, eczema, wrinkled skin, and wound healing. Some clinical trial studies have shown that the effect of curcumin on breast cancer dermatitis is beneficial(Khameneh et al., 2018; Sarkhosh et al., 2019). For example, Okunieff et al. reported curcumin might reduce cutaneous radiation toxicity in mice (Okunieff et al., 2006). Hemati et al. demonstrated that oral curcumin is effective in the prophylaxis of radiation-induced dermatitis in breast cancer (Hemati et al., 2011).  Curcumin can be considered as an effective factor in inhibiting and controlling radiation dermatitis in patients with BC and improving clinical symptoms. Curcumin might reduce radiation dermatitis severity compared to placebo through various molecular pathways, such as reducing the levels of inflammatory cytokines.

Recent Progress in Understanding the Health Benefits of Curcumin
Molecules | March 2023
Among natural compounds, curcumin, the main active component isolated from the rhizome of Curcuma Longa L., is well known for its beneficial effect on human health. Various biological activities and therapeutic properties of curcumin are due to its chemistry; in particular, phenolic hydroxyl groups, the central bis-α, β-unsaturated β-diketone, double conjugated bonds, and methoxy groups are responsible for its bio-pharmacological effects.  Inflammaging is a word used to describe the tight relationship between low-grade chronic inflammation and aging that occurs during physiological senescence in the absence of evident infection. This condition has been linked to a broad spectrum of age-related disorders in various organs, including the brain. Inflammaging represents a highly significant risk factor for the development and progression of age-related conditions, including neurodegenerative diseases characterized by the progressive dysfunction and degeneration of neurons in the brain and peripheral nervous system. In the brain, curcumin acting on microglia can inhibit the formation of reactive oxygen species and other pro-inflammatory mediators that are believed to play a pivotal role in many age-related diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease. The studies presented in this Special Issue have confirmed the multiple proprieties of curcumin that are beneficial to human health. Our results suggest that curcumin supplementation or curcumin supplementation together with a combined change in dietary habits and/or implementation of physical activity and/or lifestyle changes has positive effects on the levels of certain blood biochemical parameters and waist circumference.

 Meta-Analysis of Exploring the Effect of Curcumin Supplementation with or without Other Advice on Biochemical and Anthropometric Parameters in Patients with Metabolic-Associated Fatty Liver Disease (MAFLD)
International Journal of Environmental Research and Public Health | March 2023
Curcumin is characterized by many desirable properties. It has anti-inflammatory, antioxidant, and anticancer properties, among others. Furthermore, importantly, it is safe and rarely causes adverse symptoms. For this reason, it is used to treat or support the treatment of many diseases, e.g., cardiovascular diseases, inflammatory bowel diseases, breast, stomach, pancreatic and lung tumors, dermatoses, allergic asthma, and liver diseases. The use of curcumin supplementation or curcumin supplementation together with changes in diet, lifestyle, and/or physical activity led to statistically significant positive changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting blood insulin (FBI), homeostasis model assessment of insulin resistance (HOMA-IR), total triglycerides (TG), total cholesterol (TC), and waist circumference (WC). It appears that these therapeutic approaches may be effective in alleviating Metabolic-Associated Fatty Liver Disease (MAFLD).

The Differential Antagonistic Ability of Curcumin against Cytotoxicity and Genotoxicity Induced by Distinct Heavy Metals
Toxics | March 2023
Curcumin exhibits various beneficial biological activities including being anti-oxidant, anti-inflammatory, anti-tumor, and anti-bacterial. A series of authoritative international institutions, such as the Food and Drug Administration (FDA) in the USA and the Joint FAO/WHO Expert Committee on Food Additives, have confirmed the safety of curcumin in daily use and clinical treatment. Depending on the outstanding biological properties, curcumin is increasingly employed to antagonize heavy metals’ adverse effects, mainly through anti-oxidation and metal chelation. For instance, curcumin had been shown to have many therapeutic properties on cadmium-induced organ toxicity by removing ROS and inhibiting oxidative damage. In addition, Kabeer Abubakar et al. showed that curcumin attenuates Pb-induced neurotoxicity by inhibiting oxidative stress and chelating Pb ions. Curcumin shows prominent detoxification specificity against different types of heavy metals and toxic endpoints, which provides a new clue for the better and targeted application of curcumin in heavy metal detoxification.  The protective efficacy of curcumin for Cd- and As-induced toxicity was more obvious than for Pb and Ni. Both anti-oxidation and metal chelation contributed to the antagonistic efficiency of curcumin against heavy metals. Considering the remarkable bioactivity and wide application of curcumin in biomedicine, it is worthwhile to further investigate the protective effect of curcumin against many other contaminants and elucidate the underlying mechanism in vitro and in vivo.

Curcumin effects on chronic obstructive pulmonary disease: A systematic review
Health Science Reports | March 2023
Curcumin has antiproliferative and anti-inflammatory effects by downregulating pro-inflammatory cytokines. Besides, Curcumin accelerates the transcription of genes which helps the expression of the antioxidant system by reducing reactive oxygen species  and leading to an increase in the antioxidant defense system. Adding or replacing Curcumin, a natural meal flavoring, may indicate advantages in this era by its antiproliferative and anti-inflammatory effects. Curcumin can inhibit alveolar epithelial thickness and proliferation, lessen the inflammatory response, remodel the airway, produce ROS, alleviate airway inflammation, hinder emphysema and prevent ischemic complications. The findings of our study suggest that Curcumin might be potentially a beneficial food additive and could be effective in treating chronic obstructive pulmonary disease for alternation or addition to previous pharmacological managements. It has been demonstrated that this impact is related to Curcumin's modulatory effects on oxidative stress, cell viability, and inflammation.

Curcumin: a natural organic component that plays a multi-faceted role in ovarian cancer
Journal of Ovarian Research | March 2023
Curcumin, a natural organic component obtained from Curcuma longa’s rhizomes, shows abundant anti-tumor, antioxidant and anti-inflammatory pharmacological activities, among others. Notably the anti-tumor activity has aroused widespread attention from scholars worldwide. Numerous studies have reported that curcumin can delay ovarian cancer, increase its sensitivity to chemotherapy, and reduce chemotherapy drugs’ side effects. It has been shown considerable anticancer potential by promoting cell apoptosis, suppressing cell cycle progression, inducing autophagy, inhibiting tumor metastasis, and regulating enzyme activity. Around 210 clinical trials on curcumin application have been documented. Several clinical trials have shown that curcumin has beneficial effects on serum markers of inflammation, weight loss and glucose and lipid metabolism. Among other roles, this natural polyphenolic compound acts as an antioxidant, anti-aging, anti-inflammatory, lipid-modifying. As a broad-spectrum anticancer drug, has been reported to selectively kill cancer cells through various biological pathways without toxic side effects on normal cells. These biological pathways include the induction of apoptosis, cell cycle arrest, effects on autophagy, inhibition of tumor cell metastasis, regulation of enzyme activity and inhibition of the inflammatory response. Clinical trials have shown that curcumin does not have toxic and side effects at a dose of 8 g per day, which indicates its safety.

The effect of curcumin-piperine on cardiometabolic, inflammatory and oxidative stress factors and macular vascular density
Avicenna Journal of Phytomedicine | March 2023
Curcumin is a safe phytochemical with antioxidant, anti-inflammatory, antidiabetic, and lipid-lowering effects. The combination of curcumin with piperine (an alkaloid derived from the plant Piper nigrum L.) has better gastrointestinal absorption and reduces curcumin's systemic excretion. Piperine increases the bioavailability of curcumin by binding to the enzyme glucuronidase in the intestine, preventing glucuronidation and reducing the excretion of curcumin from the stool (Kaur, 2012). No significant adverse effects are associated with supplementation with curcumin, even at doses above 8 g/day (Mirzaei et al., 2017). Many regulatory proteins, including chemokines, interleukins, hematopoietic growth factors, and transcription factors, are modulated by curcumin, thus reducing the inflammatory process (Peddada et al., 2019). In several studies, curcumin has been shown to downregulate tumor necrosis factor (TNF) -α (Li et al., 2013) and C- reactive protein (Adibian et al., 2019). Curcumin supplementation improved glycemic factors, low-density lipoprotein, very low-density lipoprotein, and triglycerides in patients with diabetes (Neerati et al., 2014). It also significantly lowered blood glucose levels (Nabavi et al., 2015) and modulated retinal disorders in diabetic rats. If the beneficial effects of curcumin on diabetic retinopathy are observed, this safe, this natural and inexpensive herbal supplement can be considered a therapeutic solution in these patients.

Protective effects of curcumin and Ginkgo biloba extract combination on a new model of Alzheimer’s disease
Inflammopharmacology | March 2023
Several experimental and clinical investigations have shown that curcumin and its new formulations protect against Alzheimer’s disease (Antona et al. 2021). Curcumin has been proven to have antioxidant, anti-inflammatory, and neurotrophic properties, as well as the ability to suppress apoptosis and hyper-phosphorylation of tau protein (Yang et al. 2022). Our results provide strong evidence for the hypothesis that ginkgo biloba extract increases curcumin's plasma bioavailability and brain access, which may improve curcumin’s effectiveness against characteristic symptoms of Alzheimer’s disease. Moreover, it may support the idea that ginkgo biloba extract and curcumin may be used together to prevent the central pathological changes that result in the occurrence of Alzheimer’s disease, and arrest the progression of Alzheimer’s disease successfully.

The impact of curcumin supplementation on systemic lupus erythematosus and lupus nephritis: A systematic review
Lupus | March 2023
Curcumin is the active ingredient in the curry spice turmeric. It has anti-inflammatory properties due to the inhibition of transcription factors and inflammatory mediators such as nuclear factor-κβ (NF-κβ), cyclooxygenase-2 (COX2), lipoxygenase (LOX), tumor necrosis factoralpha (TNF-alpha), and interleukin-1 (IL-1) and 6 (IL-6). Another study suggested that curcumin reduced B cell-activating factor (BAFF) when used for up to 8 weeks at 50 mg/kg/day. A reduction in pro-inflammatory Th1 and Th17 percentages, IL-6 and anti-nuclear antibody (ANA) levels were reported.

Curcumin Mitigates Neuropathic-Induce Muscle Atrophy
International Journal of Exercise Science | March 2023
Curcumin has been shown to exert an anti-inflammatory effect, preserving muscle mass in diabetic rats. Curcumin supplementation appears to mitigate this inflammatory response and muscle mass loss.

Multiple mechanisms of curcumin targeting spinal cord injury
Biomedicine & Pharmacotherapy Volume | March 2023
Curcumin acts as an anti-inflammatory, antioxidant, anti-apoptotic and neuroprotective agent in secondary spinal cord injury through multiple pathways. As the main active ingredient in turmeric, curcumin can play an important role in reducing inflammation and oxidation, protecting the neurons, and ultimately reducing spinal cord injury. This article reviews the effects of curcumin on the repair of nerve injury, with emphasis on the various mechanisms by which curcumin promotes the treatment of spinal cord injury.

Efficacy of curcumin plus piperine co-supplementation in moderate-to-high hepatic steatosis: A double-blind, randomized, placebo-controlled clinical trial
Phytotherapy Research | February 2023
Curcumin + piperine decreased waist circumference, systolic blood pressure, total cholesterol, low-density lipoprotein-cholesterol, fasting blood glucose, alanine transaminase and aspartate transaminase compared with placebo. Curcumin + piperine may be considered as an adjunct therapy to improve anthropometric measures, blood pressure, lipid profile, blood glucose, and liver function in NAFLD patients.

Curcumin-piperine co-supplementation and human health: A comprehensive review of preclinical and clinical studies
Phytotherapy Research | February 2023
The findings of this comprehensive review show the beneficial effects of curcumin-piperine in improving glycemic indices, lipid profile and antioxidant status in diabetes, improving the inflammatory status caused by obesity and metabolic syndrome, reducing oxidative stress and depression in chronic stress and neurological disorders, also improving chronic respiratory diseases, asthma and COVID-19.

Curcumin a Natural Phenol and Its Therapeutic Role in Cancer and Photodynamic Therapy: A Review
Pharmaceutics | February 2023
Dietary-derived polyphenolic compounds such as curcumin are stated to have anticancer potential and related pharmacological benefits and receive enormous attraction because of their beneficial health impact. Curcumin is an extremely pleiotropic molecule that can mediate cancer treatment as a chemopreventive or chemotherapy agent without side effects. Curcumin and other turmeric-derived products are labeled as safe by the Food and Drug Administration (FDA, USA), and curcumin has achieved therapeutic pursuit in treating metabolic diseases, immune-related diseases, and cancer, owing to its vast biological target and with practically no aftereffects. The structural characteristics of curcumin improve its ability to bind with various biomacromolecules.

Mesenchymal Stem Cells and Curcumin Effectively Mitigate Freund's Adjuvant-induced Arthritis via their Anti-inflammatory and Gene Expression
Endocrine, Metabolic & Immune Disorders | February 2023
Curcumin and BM-MSCs work together to dramatically  restore the high serum PGE2 and IL-17 levels and lower the IL-13 level in arthritic rats to normal levels. Based on these findings, additive therapeutic effects on rheumatoid arthritis occur from the combined treatment of curcumin and BM-MSCs compared with their individual us. Thus, it can be said that both curcumin and BM-MSCs are effective at reducing inflammation while also having beneficial effects on the ankle joint, thymus and spleen.

Modulatory properties of curcumin in cancer: A narrative review on the role of interferons
Phytotherapy Research | February 2023
Curcumin, the active ingredient of turmeric, is one of these herbal remedies with many beneficial effects, including modulation of immunity. Curcumin is beneficial in managing various chronic inflammatory conditions, improving brain function, lowering cardiovascular disease risk, prevention and management of dementia, and prevention of aging. Several clinical studies have supported this evidence, suggesting curcumin to have an immunomodulatory and anti-inflammatory function.

The effect of Curcumin on metabolic parameters and androgen level in women with polycystic ovary syndrome: a randomized controlled trial
BMC Endocrine Disorders | February 2023
Recently curcumin was studied as supportive therapy for a wide range of diseases such as type 2 diabetes which is one of the complications of polycystic ovary syndrome PCOS. Based on a study on animals, curcumin can be effective in improving insulin sensitivity and decreasing CRP and IL-6 levels. Moreover, it was reported in a study on humans that the edible intake of curcumin led to a significant decrease in FBS, HOMA-IR, HbA1c, triglycerides, and total cholesterol levels in patients with metabolic diseases. As seen in animal experiments, the use of curcumin can lead to a decrease in insulin resistance (one of the key features of polycystic ovary syndrome PCOS phenotype), a decrease in blood’s inflammatory factors such as CRP and IL-6. The administration of curcumin can lead to improvement in insulin sensitivity, cholesterol levels and metabolic factors in people with polycystic ovary syndrome PCOS as well. Curcumin decreased FBS levels and improved menstruation characteristics (amenorrhea, oligomenorrhea, and menstrual irregularities) in women with polycystic ovary syndrome PCOS. After the intervention, amenorrhea and oligomenorrhea frequency in the curcumin group was significantly lower than in the placebo group. After 12 weeks of intervention, the mean serum FBS levels in the curcumin group were significantly lower than in the placebo group.

Impacts of turmeric and its principal bioactive curcumin on human health: Pharmaceutical, medicinal, and food applications: A comprehensive review
Frontiers In Nutrition | February 2023
Recently, the biological activities of turmeric and curcumin have been thoroughly investigated. The studies mainly focused on their antioxidant, antitumor, anti-inflammatory, neuroprotective, hepatoprotective, and cardioprotective impacts. Over the few current decades, considerable studies have been conducted on curcumin due to its beneficial health properties, including potent antioxidant properties, antimicrobial, anti-inflammation, anticancer effects, cardio-protectiveness, and hypoglycemic action. Curcumin has a prolonged history of usage in ancient medicine, where it was used in various medical treatments as well as food coloring and spice. Science has advanced over time, demonstrating curcumin’s many positive benefits for human health. Technological advances have made it possible to employ curcumin for various uses in the food and health industries. According to the results of preclinical and clinical studies conducted in vitro and in vivo, respectively, curcumin may be helpful in the prevention and treatment of many diseases, including cardiovascular diseases, diabetes mellitus, obesity, allergy, asthma, inflammatory diseases, and neurodegenerative disorders, e.g., Alzheimer’s, Parkinson’s, multiple sclerosis, and Huntington’s disease by affecting different molecular targets. Compared to other medications, curcumin is viewed as a very cost-effective and safe natural substance that can be used to prevent and treat many disorders. Black pepper piperine is one of the most effective boosters of curcumin bioavailability. The simultaneous administration of curcumin and piperine to humans or animals boosted the serum levels by more than a thousandfold. Piperine contained in black pepper can improve the uptake of curcumin by 2,000% (20 times). The vast metabolism of turmeric in the hepatic tissues and intestinal walls increased its bioavailability, which improved through piperine. Taking these two substances with an oil rich in unsaturated fatty acids further strengthens this benefit. Zeng et al. examined the effect of piperine pre-administration on oral curcumin bioavailability. In this investigation, rats were given 20 mg/kg piperine first, followed by 200 mg/kg curcumin at intervals of 0.5–8 h after piperine treatment. The pre-treatment with piperine before curcumin administration significantly increased curcumin oral bioavailability in all tested rats. Recent research suggests that oral administration of curcumin and piperine for symptomatic COVID-19 therapy might dramatically reduce mortality and morbidity (53). The conjugation between piperine and curcumin may be a safe and natural option for preventing post-COVID symptoms.

The Role of Curcumin as an Anti-Aging Compound
Emerging Anti-Aging Strategies | February 2023
Compounds that may postpone the onset of age-related symptoms, particularly natural compounds included in the average diet, are being thoroughly researched and Curcumin is one among them. It alleviates age-related symptoms, increases the lifetime of model organisms, and delays the course of age-related disorders in which cellular senescence is directly implicated.

Anticancer properties of curcumin-treated Lactobacillus plantarum against the HT-29 colorectal adenocarcinoma cells
Scientific Reports | February 2023
When taken orally or topically, curcumin has a number of anti-inflammatory and anticancer properties. At both neutral and acidic pH levels, curcumin possesses potent antioxidant properties. It also influences cell signaling, enzyme activity, immunomodulation, angiogenesis, and cell–cell adhesion. Curcumin’s ability to modulate gene transcription and induce apoptosis in preclinical models suggests that it may be especially useful for cancer chemoprevention and chemotherapy in humans. Evidence of biologically active levels in both animals and humans has been demonstrated. Oral curcumin has already been studied extensively, and it appears to have the potential to help people with invasive or pre-invasive gastrointestinal tract cancers, particularly those of the colon and rectum.  Curcumin may affect the metabolomics of probiotics in intestinal flora which could subsequently influence their anticancer properties. The findings in this study suggest that the metabolomics of curcumin-treated probiotics may either directly induce enhanced toxicity against cancer cells or may interact with curcumin indirectly, amplifying their anticancer effects.

The Therapeutic Role of Curcumin in Inflammation and Post-Surgical Outcomes
Food Reviews International | February 2023
Curcumin is a natural polyphenol derivative that showed to target multiple signaling molecules at the cellular level and help in supporting health benefits by acting as a potent anti-inflammatory and antioxidant compound. It has been shown to be beneficial in the treatment of inflammatory conditions,  metabolic syndrome,  wounds, post-surgical inflammation and outcomes. Curcumin has remarkable antioxidant and anti-inflammatory properties because it  inhibits inflammatory mediators. Curcuminoids as a preventative agent against myocardial infarction after coronary artery bypass grafting (CABG) were evaluated; C-reactive protein, plasma malondialdehyde, and N-terminal pro-B type natriuretic peptide levels were all significantly lower in curcumin when compared to the placebo group. Curcumin by itself has very low bioavailability due to ineffective absorption, and fast metabolism and excretion. This issue can be solved by combining curcumin with piperine (a key active ingredient in black pepper) to create a curcumin complex that is readily absorbed and metabolized in the body. Other in-vitro studies have also demonstrated additional evidence supporting the cardioprotective effect of curcuminoids is that they inhibit human platelet activation which eventually lead to decreased occurrence of myocardial ischemia. Curcumin’s antioxidant properties were found to reduce adriamycin-induced cardiotoxicity and may help prevent diabetic cardiovascular complications. Curcumin also has an anti-thrombotic, anti-proliferative, and anti-inflammatory properties, and can lower serum cholesterol levels, all of which may protect against atherosclerosis.  In animal models, curcumin have been shown to reduce the development of cardiac hypertrophy and heart failure. Curcumin has been shown to have strong antioxidant and anti-inflammatory effects that could result in improved post-surgical outcomes. In conclusion, this review paper shows that curcumin is highly beneficial and has strong antioxidant and anti-inflammatory effects that could result in improved post-surgical outcomes. These benefits are maximized when curcumin is coupled with agents such as piperine, that significantly increase its bioavailability.

Curcumin Induces Ferroptosis in Follicular Thyroid Cancer by Upregulating HO-1 Expression
Oxidative Medicine and Cellular Longevity | February 2023
Curcumin has anticancer effects in multiple types of solid tumors. Research has demonstrated that curcumin has potential applications in pharmacology and cancer treatment. Curcumin inhibits cancer cell growth and promotes apoptosis in colorectal cancer, lung cancer, and prostate cancer. Additionally, numerous studies have shown that curcumin elevates the HO-1 expression in a wide range of cancer cells. Tumorigenesis is significantly inhibited by curcumin. The present study shows that curcumin inhibits the growth of follicular thyroid cancer by increasing the HO-1 expression, further activating the ferroptosis pathway. This study demonstrates that the HO-1-ferroptosis signalling pathway might play an important role in follicular thyroid cancer tumorigenesis, and that curcumin inhibits the growth of follicular thyroid cancer cells by affecting this pathway.  We conclude that curcumin inhibits the tumorigenesis of follicular thyroid cancer via HO-1-induced activation of the ferroptosis signalling pathway. Further research is needed to determine the specific mechanism underlying the effect of curcumin on follicular thyroid cancer; however, for patients who cannot tolerate surgery or are difficult to diagnose, it may be possible to develop a therapeutic pathway towards the remission of follicular thyroid cancer based on our findings.

Curcumin inhibits pancreatic cancer cell proliferation
Journal of Gastrointestinal Oncology | January 2023
In hypoxic pancreatic cancer cells, curcumin can inhibit the HIF-1α-mediated glycolytic pathway by down-regulating Beclin1 expression, thereby inhibiting cell proliferation. Furthermore, curcumin reduced cellular adenosine triphosphate (ATP) production in a dose-dependent manner. Compared with control pancreatic cancer cells, the expression levels of GLUT1, HK2, LDHA, and PDK1 gradually decreased with increasing curcumin concentrations. Curcumin can inhibit the expression of Beclin1 and HIF-1α in pancreatic cancer cells under anoxic conditions, thereby affecting the glycolysis pathway and inhibiting cell proliferation.

Exploring the Neuroprotective Mechanism of Curcumin Inhibition of Intestinal Inflammation against Parkinson’s Disease Based on the Gut-Brain Axis
Pharmaceuticals | January 2023
Curcumin is an important active ingredient of turmeric with a wide range of pharmacological effects, such as antitumor, antioxidant, anti-inflammatory, antibacterial, and hypolipidemic properties. In addition, curcumin promotes Parkinson’s disease treatment through multiple pathways, including the prevention of reactive oxygen species (ROS) production, glial cell activation, a-syn aggregation, neuronal cell apoptosis.  Cui et al. suggested that curcumin may have more important peripheral effects than direct effects on the central nervous system. Curcumin is known to improve intestinal barrier function and reduce inflammation. In a previous study, curcumin was considered neuroprotective in PD, and this neuroprotective mechanism may act by inhibiting intestinal inflammation.  After treatment with curcumin, the total movement distance and average speed improved, the tyrosine hydroxylase (TH) rate in the substantia nigra pars compacta (SNpc) and striatum were reduced, the pyroptosis of AIM2 and caspase-1 activations were inhibited, and intestinal inflammatory factors and intestinal inflammation were reduced. Curcumin improved gastrointestinal disorders and gastrointestinal barrier function in the MPTP-induced mice and reversed MPTP-induced motor dysfunction and dopaminergic neuron loss in mice. The above effects may be partly dependent on curcumin activation of the SIRT1/NRF2 pathway in the colon. This study provides a potential opportunity to develop new preventive measures and novel therapeutic approaches that could target the gut–brain axis in the context of PD and provide a new intervention in the treatment of Parkinson’s disease. In summary, curcumin can inhibit intestinal pyroptosis through activation of the SIRT1/NRF2 pathway; reduce intestinal tissue secretion of IL-1β, IL-6, IL-18, and TNFα; and attenuate the loss of gastrointestinal barrier proteins ZO-1 and occludin, elucidating that curcumin is dependent on the gut–brain axis and thus exerted neuroprotective effects.

Curcumin’s anti-cancerous activity
Williams Cancer Institute | January 2023
For over 5000 years plants have been used as medicine and therapies and nowadays a fair amount of modern medicine is directly or indirectly derived for plants. There are many plant-derived compounds that can induce apoptosis in cells; these compounds are non-toxic for our body and are capable of boosting apoptotic pathways. Curcumin found in turmeric has been found to have many properties including anti-inflammatory, anti-oxidant, and anti-carcinogenic. The influence of Curcumin in treating cancer relies on its effect on cell proliferation, cell survival, caspase activation, death receptors, mitochondrial, protein kinase and tumor suppression pathways; so through this interactions, its able to suppress tumor cells initiation, progression and metastasis. One of its best qualities is that curcumin is toxic for cancer yet cytoprotective for normal cells, making it universal for all kind of cancer cells, proving positive effects on breast, lung, prostate, pancreatic, oral, colorectal, multiple myeloma and head and neck squamous cell carcinoma Also, it’s been shown that people from southwest Asia who regularly consume turmeric in their diet, have the lowest incidence of any type of cancer. Despite its actual mechanism against cancer is still unknown so far it has demonstrated to be a good, natural and safe adjuvant in cancer treatment.

Attenuation of Inflammatory Responses in Breast and Ovarian Cancer Cells by a Novel Chalcone Derivative and Its Increased Potency by Curcumin
Mediators of Inflammation | January 2023
Curcumin, is extensively studied for its various pharmacological effects, including anticancer properties. Curcumin has shown promising results in treating cancer, both alone and in combination with other chemotherapeutic agents. It exerts anticancer effects, mainly by modulating various signaling pathways and transcription factors. Curcumin is a well-known natural product with numerous pharmacological effects, especially in cancer.  It has been shown in recent studies that curcumin inhibits cell proliferation, promotes apoptosis, suppresses chemotherapeutic resistance, and exerts antimetastatic effects in the treatment of both breast and ovarian cancers, either alone or combined with other chemotherapeutic agents. In conclusion, our findings suggest that MPP, a novel synthetic derivative of chalcone, alone or in combination with curcumin, could serve as an effective anti-inflammatory and cytotoxic treatment for combating breast and ovarian cancer, mediated by the inhibitory effect of this combination on NF-κB activity and its downstream genes. All the effects of MPP were enhanced by the addition of curcumin. MPP, especially when combined with curcumin, caused a remarkable increase in the concentration of IκB.  MPP and its coadministration with curcumin effectively reduced the activity of the NF-κB signaling pathway, leading to a reduced inflammatory response in the environment of cancer cells.

Curcumin for the treatment of COVID-19 patients: A meta-analysis of randomized controlled trials
Phytotherapy Research | January 2023
Curcumin is a low-cost and easily accessible therapeutic option for COVID-19 patients. Curcumin reduced the risk of all-cause mortality (RR 0.38; 95% CI: 0.20–0.72; moderate certainty of evidence), and patients with no recovery status (RR 0.54; 95% CI: 0.42–0.70; moderate certainty of evidence). The results of subgroup analysis suggested a higher benefit with early administration of curcumin (within 5 days of onset of symptoms) and with the use of combination regimens. Curcumin is likely to be of benefit in mild-to-moderate COVID-19 patients.

Inhibiting proliferation and migration in cervical cancer by curcumin and resveratrol
Natural Product Research | January 2023
Functional experiments indicated that curcumin displayed stronger inhibitory activity on the proliferation of cervical cancer HeLa cells. Curcumin exerted its anti-cervical cancer effect by regulating cell cycle mitosis, whereas resveratrol affected adhesion. Furthermore, the target genes were verified by molecular docking, qRT-PCR, and Western blot, the results revealed that curcumin and resveratrol significantly decreased the expression of CHEK1 and MAPK3, respectively. In conclusion, curcumin inhibited the proliferation of cervical cancer HeLa cells by specifically targeting CHEK1, while resveratrol specifically targeted MAPK3 to supress migration, and the combination of them can synergistically restrain the proliferation and migration of cervical cancer cells.

Curcumin treatment suppresses cachexia-associated adipose wasting in mice by blocking the cAMP/PKA/CREB signaling pathway
Phytomedicine | January 2023
Curcumin significantly reduced serum levels of free fatty acids and increased triglyceride levels. In addition, curcumin significantly inhibited PKA and CREB activation in the adipose tissue of cancer cachectic mice. Curcumin also ameliorated CL316243-induced adipose atrophy and inhibited hormone-mediated PKA and CREB activation in mice. Moreover, the lipid droplet degradation induced by C26 tumor cell conditioned medium in mature 3T3-L1 adipocytes was ameliorated by curcumin treatment. Curcumin also improved the lipid droplet degradation of mature 3T3-L1 adipocytes induced by CL316243. Curcumin might be expected to be a therapeutic supplement for cancer cachexia patients, primarily through inhibiting adipose tissue loss via the cAMP/PKA/CREB signaling pathway. Curcumin alleviated cancer cachexia-associated adipocyte atrophy and lipid degradation. The protective effects of curcumin on cachectic fat loss are mediated by the cAMP/PKA/CREB signaling pathway.

Curcumin suppresses cell proliferation and reduces cholesterol absorption
Lipids in Health and Disease | January 2023
Curcumin is a bioactive dietary polyphenol of turmeric with various biological activities against several cancers. Several studies have demonstrated the protective effects of Curcumin against varied cancers, including lung cancer, breast cancer, gastric cancer, colorectal cancer and so on. In addition, an epidemiological analysis showed an association between dietary consumption of Curcumin and decreased incidence of colorectal cancer in the Indian population. Several potential mechanisms of curcumin-related anti-cancer effects in colorectal cancer have been identified, such as mechanisms involving DNA damage, cell cycle arrest, apoptosis, colorectal cancer angiogenesis, epidermal growth factor receptor signaling pathway, and tumor immunomodulation. Furthermore, Zou J. et al found that curcumin could reduce intestinal cholesterol absorption by 51% in mice. Studies have demonstrated the potential anti-tumor effects of curcumin on CRC. In summary, the present study demonstrates that curcumin suppresses the proliferation of Caco-2 cells and reduces cholesterol absorption through activate the TRPA1 channel. Furthermore, the potential antitumor effect of curcumin in a high-lipid environment was determined. Curcumin is a bioactive dietary polyphenol that exhibits anticancer and lipid-lowering effects in vitro. Curcumin could serve as a natural active ingredient to be used in the primary prevention of colorectal cancer in clinical practice.

Curcumin enhances the anti-cancer efficacy of paclitaxel in ovarian cancer
Frontiers | January 2023
Curcumin has been shown to synergistically enhance the therapeutic effects of multiple chemotherapeutic agents, but the potential involvement of curcumin in ovarian cancer is largely unknown. Curcumin and paclitaxel synergistically inhibited proliferation and promoted apoptosis in ovarian cancer cells. Furthermore, curcumin and paclitaxel combination resulted in decreased miR-9-5p expression and increased BRCA1 expression. Functionally, miR-9-5p overexpression counteracted the synergistic effect of curcumin and paclitaxel on cell proliferation and apoptosis by targeting BRCA1. Meanwhile, in vivo experiments revealed that curcumin and paclitaxel combination dramatically suppressed the growth of transplanted tumors, while miR-9-5p mimics eliminated the growth inhibition of xenografts induced by the combined treatment. Conclusion: Curcumin enhanced the anti-cancer efficacy of paclitaxel in ovarian cancer by regulating the miR-9-5p/BRCA1 axis. These findings provide strong evidence for clinical investigation of curcumin and paclitaxel combination as a novel strategy for ovarian cancer patients.

MiR-125b-5p is targeted by curcumin to regulate the cellular antioxidant capacity
Free Radical Research | January 2023
As a natural polyphenolic food supplement and the principal curcuminoid in turmeric, curcumin shows antioxidant, anti-inflammatory, and antitumor activities.  Cellular antioxidant capacity induced by curcumin extract was inhibited by miR-125b-5p overexpression. Thus, curcumin may exhibit antioxidant effects by repressing miR-125b-5p expression, which provides new insights into the molecular antioxidant mechanism of curcumin.

Curcumin Stimulates UCP1-independent Thermogenesis in 3T3-L1 White Adipocytes but Suppresses in C2C12 Muscle Cells
Biotechnology and Bioprocess Engineering | January 2023
The anti-obesity effect of curcumin involves mainly two interacting parts, one mediated via β3-AR and cAMP (UCP1-dependent) and the other via α1-AR and increase in cytosolic Ca2+ levels (UCP1-independent) in beige fat but not in muscle cells.

Curcumin Reduces Pathological Endoplasmic Reticulum Stress
International Journal of Molecular Sciences | January 2023
Several published studies show that curcumin treatment reduces ER stress in a range of conditions. We can identify a “natural” chemical, curcumin, which is able to reduce pathological ER stress in a cell model of EDM5 by promoting the proteasomal degradation mutant matrilin-3. Therefore, this is an important in vitro study in which we describe, for the first time, the success of a naturally occurring chemical as a potential treatment for this currently incurable rare skeletal disease. This is an important and exciting area of research that will have significant clinical impact on a range of human diseases including the rare skeletal disease, EDM5.

The Effects of Curcumin on Inflammasome: Latest Update
Molecules | January 2023
Curcumin, a natural monomer extracted from plants, has gained popularity in recent decades due to its therapeutic benefits in a wide range of human pathological conditions. The medicinal plant Curcuma longa Linn, a perennial herb of the Zingiberaceae family known as “golden spice” for its broad spectrum of pharmacological properties, contains curcumin as one of its most active constituents. In addition, the chemical structure of curcumin makes it an excellent scavenger of reactive oxygen and nitrogen species (ROS and RNS, respectively). As a result, curcumin can attenuate or prevent exercise-induced oxidative stress and inflammation. Curcumin activates the Nrf2 pathway, which is important for the activation of antioxidant enzymes . Curcumin is well known to have anti-inflammatory effects, and its role in modulating neuroinflammation in several neurological disorders has been extensively described. Taken together, in vitro, in vivo, and clinical studies confirmed curcumin’s promising effects for attenuating inflammation and oxidative stress, alleviating the patient’s pain, protecting joints from damage, and improving the quality of life of rheumatoid arthritis patients without side effects. Curcumin encapsulation in nanoparticles or in combination with MSCs showed an effective and promising strategy for increasing curcumin bioavailability and efficacy in rheumatoid arthritis. In addition, new curcumin formulations and administration routes (such as oral and topical) have been proposed as effective strategy for treating rheumatoid arthritis. In this review, we have focused on the therapeutic effects of curcumin administration in various inflammatory diseases, focusing on its functional mechanisms in preventing activation of the NLRP3 inflammasome. Future research will address the clinical application of curcumin to treat diseases in which the inflammasome is activated.

Review of Curcumin and Its Different Formulations: Pharmacokinetics, Pharmacodynamics and Pharmacokinetic-Pharmacodynamic Interactions
OBM Integrative and Complementary Medicine | January 2023
Curcumin has many pharmacological activities, such as antioxidant, anti-inflammatory, antibacterial, antiviral, antidiabetic, anticancer, and immunomodulatory activities, against neurological disorders as well as digestive disorders. Curcumin acts as an antioxidant by potentially scavenging various free radicals, such as reactive oxygen and nitrogen species, and inhibiting lipoxygenase/cyclooxygenase and xanthine dehydrogenase/oxidase, enzymes that are thought to generate reactive oxygen species. In addition, it can act directly by upregulating the antioxidant defense enzymes, such as superoxide dismutase and glutathione peroxidase. Despite possessing potential pharmacological activity, as well as safety at high doses (12 g/day), curcumin therapeutics still face low bioavailability. Piperine increased the bioavailability of curcumin by 154%. Curcumin combined with piperine exhibited higher intestinal absorption (78%). When co-administered with piperine, the half-life of curcumin was increased from 12.8h to 28.9h. Co-administration of piperine (20 mg/kg) and curcumin (2 mg/kg) increased the plasma concentration of curcumin in a short time, i.e. within 1-2h, peak time was increased, elimination half-life decreased, and clearance decreased. In humans, even with a 2g load of curcumin, the serum level was undetectable. A higher extent of absorption and higher bioavailability of curcumin (2000%) was observed in humans using 20mg piperine. The pharmacological activities of curcumin and its related formulations and products have been reviewed in a few targeted disease pathologies of national concern, such as cancer, gastroduodenal disorder, immunodeficiency, liver disease, ophthalmology, diabetes and osteoarthritis among other metabolic diseases, and microbial and viral infections.

Curcumin Induces Ferroptosis in Follicular Thyroid Cancer by Upregulating HO-1 Expression
Oxidative Medicine and Cellular Longevity | January 2023
Research has demonstrated that curcumin has potential applications in pharmacology and cancer treatment. Curcumin inhibits cancer cell growth and promotes apoptosis in colorectal cancer, lung cancer, and prostate cancer. Additionally, numerous studies have shown that curcumin elevates the HO-1 expression in a wide range of cancer cells. The present study shows that curcumin inhibits the growth of FTC by increasing the HO-1 expression, further activating the ferroptosis pathway. This study demonstrates that the HO-1-ferroptosis signalling pathway might play an important role in FTC tumorigenesis, and that curcumin inhibits the growth of FTC cells by affecting this pathway. We conclude that curcumin inhibits the tumorigenesis of FTC via HO-1-induced activation of the ferroptosis signalling pathway. Further research is needed to determine the specific mechanism underlying the effect of curcumin on FTC; however, for patients who cannot tolerate surgery or are difficult to diagnose, it may be possible to develop a therapeutic pathway towards the remission of FTC based on our findings.

Curcumin supplementation contributes to relieving anthropometric and glycemic indices, as an adjunct therapy: A meta-research review of meta-analyses
Journal of Functional Foods Volume | January 2023
Curcumin supplementation can improve anthropometric and glycemic parameters in a time- and dose- dependent manner.  Administered dose of > 1 g/day of curcumin has the most beneficial effect on anthropometric and glycemic indices. Longer durations of supplementation (>10-week) are needed to have the decreasing impact on HOMA-IR and HbA1c. Curcumin supplementation can be administered as the adjuvant therapy in managing hyperglycemia, insulin resistance, and obesity. The significant effects of Curcuma longa are primarily due to curcumin (Pulido-Moran et al., 2016).  Some beneficial effects of curcumin have been revealed, including anti-diabetic properties, antioxidant properties, and anti-inflammatory properties (Kalpana and Menon, 2004, Tsuda, 2018). Curcumin can have beneficial roles in some chronic illnesses, e.g., coronary artery disease, atherosclerosis, rheumatoid arthritis, obesity, and T2DM (Aggarwal and Harikumar, 2009, Karimi et al., 2022). The beneficial role of curcumin on glycemic control is due to its inhibitory effect on hepatic gluconeogenesis, glycogenesis, and hyperglycemia-mediated inflammation development (Ghorbani et al., 2014). Besides, it has been reported that curcumin can decrease angiogenesis in adipose tissue (Pivari et al., 2019, Seo et al., 2008), decrease pre-adipocyte differentiation by increasing resting energy expenditure by activating peroxisome proliferator- activated receptor gamma (PPAR-γ((İçer and Tek, 2021, Seo et al., 2008), reduce adipogenic genes expression (Kim et al., 2011, Lee et al., 2009), and inhibit cortisol-mediated central obesity (Hu et al., 2013). The beneficial role of curcumin on glycemic control may be stemmed from its inhibitory effect on the phosphorylation kinase enzyme involved in glycogen storage mobilization (Razavi et al., 2021). It has been demonstrated that curcumin can substantially lower FBS and HbA1c levels (Tabrizi et al., 2018; Wei et al., 2019). Curcumin can be effective in different health conditions and age groups. With moderate reliability, curcumin supplementation can be administered as the adjuvant therapy in managing hyperglycemia, insulin resistance, and obesity.

Fluoxetine and Curcumin Prevent the Alterations in Locomotor and Exploratory Activities and Social Interaction Elicited by Immunoinflammatory Activation in Zebrafish: Involvement of BDNF and Proinflammatory Cytokines
ACS Chemical Neuroscience | January 2023
The increase in proinflammatory cytokine expression causes behavioral changes consistent with sickness behavior, and this led to the suggestion that depression might be a psychoneuroimmunological phenomenon. Fluoxetine and curcumin prevented the sickness behavior induced by A. hydrophila and the increased expression of proinflammatory cytokines. Our results point to the potential of zebrafish as a translational model in studies related to neuroinflammation and demonstrate for the first time the effects of fluoxetine and curcumin on zebrafish sickness behavior.

Curcumin combined with verapamil improve cardiovascular phenotype of a Williams-Beuren Syndrome mice model reducing oxidative stress
bioRxiv | January 2023
Curcumin is a natural yellow pigment, which has attracted much attention in recent years owing to its wide spectrum of biological activities, including antioxidant, anti- inflammatory, anti-tumor, or anti-microbial activities, (Llano et al., 2019; Bozkurt et al., 2022). Besides, curcumin improved cardiovascular structure and function, especially with the normalization of systolic blood pressure and collagen deposition in rats with diet-induced metabolic syndrome (du Preez et al., 2019). In addition, curcumin has previously shown cardiac protection in front of palmitate and high fat diet mediated the activation of the nuclear factor erythroid 2 (NRF2) (Zeng et al., 2015). A combination of curcumin and verapamil significantly ameliorates the cardiovascular phenotype of a mouse model for WBS. Its efficiency is achieved through reduction of oxidative stress levels evidenced by the reduction of XOR protein levels and induction of NRF2 pathway, both in the aortic wall and LV-myocardium. Verapamil is already approved for human use, while curcumin is a natural safe product. We here shown that their combination deserves further evaluation as potential therapeutic agent to prevent the severe cardiovascular injuries occurring in human patients with WBS.

Curcumin suppresses lung cancer progression via circRUNX1 mediated miR-760/RAB3D axis
Thoracic Cancer  | December 2022
Curcumin has antioxidant, antibacterial, anti-inflammatory, and anticancer pharmacological effects, and it therefore has the potential to become an effective drug for treating arthritis, cardiovascular disease and cancer.  Studies have reported that curcumin exerts its anticancer effect by inhibiting cancer cell proliferation, metastasis, and promoting apoptosis, including lung cancer. Curcumin, as a natural phytochemical, is attracting more and more attention. The anticancer role of curcumin has previously been confirmed in hepatocellular, breast and pancreatic cancers. Here, we reveal the anticancer effect of curcumin in lung cancer  progression. Curcumin hindered proliferation, metastasis, increased the apoptosis of lung cancer cells, and restrained lung cancer tumor growth. Our results are consistent with previous studies, which indicate that curcumin is an effective substance to suppress lung cancer progression. In conclusion, our study showed that curcumin plays an anticancer role in the progression of lung cancer, which is mainly realized by circRUNX1/miR-760/RAB3D axis. Our study revealed for the first time that curcumin inhibits lung cancer progression by regulating the circRNA network, which not only provides more evidence for the anticancer role of curcumin, but also provides a new molecular target for lung cancer treatment.

Childhood obesity and curcumin: a possible effective anti-obesity adjunct
Advances in Obesity, Weight Management & Control | December 2022
Curcumin, an important compound present in the Curcuma longa L. rhizome is a lipophilic molecule that can rapidly permeate cell membranes to exert its effect. Other intervention studies that have examined the impact of dietary polyphenols including curcumin have further shown its ability to improve insulin resistance, as well as obesity-associated low grade inflammatory responses, a main determinant of the pathology of multiple chronic health conditions, and possibly caused in part by an inadequate nutrient intake that induces alterations in the lipid content of adipose tissue and activation of immune and adipose cells and others that foster local and systemic inflammation. Additional recent evidence points not only to the anti-inflammatory effects of curcumin in this regard, but also its metabolic effects that can help to relieve obesity, as well as obesity-associated chronic health conditions. Moreover, curcumin appears to have pharmacological properties that objectively lower body weight, fat mass and triglyceride levels, while enhancing energy expenditure, fat utilization, and glucose hemostasis. Unsurprisingly, among the many beneficial health affirming impacts reported for curcumin, research specifically focused on obesity and the metabolic-preventing/suppressing aspects of curcumin is growing. Curcumin in its various forms where present or administered in adequate amounts is likely to either help initiate or offset excess weight, and promote weight loss, more often than not, and via well defined cellular pathways and molecular mechanisms of action, that support its apparent ameliorating effect on inflammation and diabetes extent, especially in cases with early onset obesity, or where losing weight via traditional interventions may be a perpetual ‘losing’ battle. Among the potential mechanisms for offsetting some degree of obesity, and its ramifications, the role of the spice known as curcumin currently appears to exhibit very favorable promise based on its ability to interact at the cellular and molecular level, and attested to in most emergent cellular, preclinical and clinical data sets that could be adapted to support the idea of personalized and precision medicine.

Curcumin inhibits pancreatic cancer cell proliferation by regulating Beclin1 expression and inhibiting the hypoxia-inducible factor-1α- mediated glycolytic pathway
Journal of Gastrointestinal Oncology | December 2022
Curcumin has a wide range of antioxidant and anti-inflammatory activities, as well as inhibition of the mitochondrial cascade. Additionally, it has shown significant antitumor activity. In conclusion, in hypoxic pancreatic cancer cells, curcumin can inhibit the HIF-1α-mediated glycolytic pathway by down-regulating Beclin1 expression, thereby inhibiting cell proliferation.

Micronutrient Supplementation to Reduce Cardiovascular Risk
Journal of the American College of Cardiology | December 2022
Curcumin, flavanol, genistein, and quercetin showed moderate- to high-quality evidence for reducing CVD risk factors. Supplementation of some but not all micronutrients may benefit cardiometabolic health. This study highlights the importance of micronutrient diversity and the balance of benefits and risks to promote and maintain cardiovascular health in diverse populations.

Not all micronutrients are created equal: Study identifies some supplements that benefit cardiovascular health
Medical Express | December 2022
A comprehensive and systematic approach to evaluate all the publicly available and accessible studies reporting all micronutrients, including phytochemicals and antioxidant supplements and their effects on cardiovascular risk factors as well as multiple cardiovascular diseases. The researchers looked at randomized, controlled intervention trials evaluating 27 different types of antioxidant supplements. They found strong evidence that several offered cardiovascular benefit. Curcumin, flavanol, genistein and quercetin showed evidence of reducing cardiovascular risk.

Curcumin Inhibits Proliferation of Renal Cell Carcinoma in vitro and in vivo by Regulating miR-148/ADAMTS18 through Suppressing Autophagy
Journal of Integrative Medicine | December 2022
Curcumin can inhibit the proliferation of renal cell carcinoma by regulating the miR-148/ ADAMTS18 axis through the suppression of autophagy in vitro and in vivo. There may exist a positive feedback loop between miR-148 and ADAMTS18 gene in RCC.

Curcumin Regulates Gut Microbiota and Exerts a Neuroprotective Effect in the MPTP Model of Parkinson's Disease
Evidence-Based Complementary and Alternative Medicine | December 2022
All curcumin groups improved cell wrinkling and vacuolar degeneration, increased the number of TH positives, improved cell survival, and the higher the dose of curcumin, the better the effect. The relative abundance of Patescibacteria, Enterobacteriaceae, Enterococcaceae all decreased in all curcumin groups. In addition, the Kyoto Encyclopedia of Genes and Genomes pathways showed a reduction in the superpathway of N-acetylneuraminate degradation after medium and high-dose curcumin administration. Curcumin regulates gut microbiota and exerts a neuroprotective effect in the MPTP mice model. This preliminary study demonstrates the therapeutic potential of curcumin for Parkinson's disease, providing clues for microbially targeted therapies for Parkinson's disease. Curcumin, a polyphenol extracted from the rhizomes of Curcuma longa, is converted into biologically active metabolites in the intestine by microbial digestion. Nowadays, it has been shown to have multiple effects such as anti-inflammatory, antioxidant, anticancer, and mitochondrial protection. The bidirectional interplay between curcumin and gut microbes has been demonstrated, as curcumin is not only metabolized by the enzymes of the gut microbes to produce active metabolites but it also strengthens the intestinal barrier and changes the composition of the gut microbes. Thus, curcumin can exert a wide range of pharmacological effects through the “microbe-gut-brain axis” and can be used to treat many chronic diseases. Curcumin has shown an extremely high therapeutic potential in Parkinson's Disease. In animal models, dyskinesia can be improved after the use of curcumin. Many studies have also confirmed that curcumin increased the survival of tyrosine hydroxylase striatal fibers and nigrostriatal dense part neurons in rat PD model induced by 6-hydroxydopamine (6-OHDA), exhibiting increased dopamine levels. Concomitantly, curcumin can exert anti-inflammatory effects by inhibiting microglia-mediated neuroinflammation and reducing interleukin-2, chemokines, and cyclooxygenase-2. Curcumin has also been shown to increase the electrical activity of hippocampal neurons in rotenone-induced Parkinson's Disease model rats and regulate the activity of mitochondrial enzyme complex. In addition, a recent clinical study found that curcumin improved motor and nonmotor symptoms and reduced the aggregation of phosphorylated α-Syn in skin biopsies in Parkinson's Disease patients. Our study shows that curcumin can effectively regulate the changes of gut microbiota, improve the dysfunction of MPTP mice, reduce the neurotoxicity of MPTP in Parkinson's Disease mice, and protect DA neurons, and there is some correlation with the dose. This preliminary study demonstrates the therapeutic potential of curcumin for Parkinson's Disease, providing clues for microbially targeted therapies for Parkinson's Disease.

Curcumin in Ulcerative Colitis
Encyclopedia.pub | December 2022
The significant anti-inflammatory properties of curcumin, being described over the years have attracted a lot of researchers’ interest, especially in the context of treating diseases with a chronic inflammation basis.  In many studies it has been shown that curcumin inhibits NF-κB expression by blocking IkappaB (IκB) kinase, that leads to the prevention of cytokine-mediated phosphorylation and the degradation of IκB, which is an NF-κB inhibitor. Furthermore, it was also reported that curcumin inhibited the activity of proinflammatory proteins (e.g., activated protein-1, peroxisome proliferator-activated receptor gamma, transcription activators, the expression of β -catenin). As oral supplementation with curcumin leads to its high concentration in the gastrointestinal tract, studies have slowly focused on its impact on the intestinal microbiota. Via this mechanism, the problem of low systemic curcumin bioavailability probably is not a significant issue within the gastrointestinal tract, and curcumin may have a hypothetical beneficial influence on the gut microbiome. A bidirectional interaction exists between curcumin and gut microbiota. Gut microbiota are actively involved in curcumin metabolism, which lead to curcumin biotransformation (demethylation, hydroxylation, demethoxylation) and the production of metabolites. Curcumin supplementation is effective in promoting the growth of beneficial bacterial strains, improving intestinal barrier functions, and counteracting the expression of pro-inflammatory mediators. Peterson et al., in a double-blind, randomized, placebo-controlled pilot study with 30 healthy subjects, assessed changes in the gut microbiota using 16S rDNA sequencing after oral supplementation with turmeric 6000 mg with extract of piperine, curcumin 6000 mg with Bioperine (black pepper extract) tablets, or placebo, at baseline and after 4 and 8 weeks. They found that both turmeric and curcumin in a highly similar manner altered the gut microbiota. Participants who took turmeric supplementation displayed a 7% increase in observed microbial species post-treatment, and curcumin-treated subjects displayed an average increase of 69% in detected bacterial species.

Protective effect of curcumin on the kidney of diclofenac sodium-challenged mice: apoptotic, redox potential and histopathological outcomes
The Journal of Basic and Applied Zoology  | December 2022
Curcumin can be used as a promising natural phytochemical in rescuing chemotherapy-associated renal dysfunction owing to its redox stabilizing and cytoprotective nature. In folk medicine, curcumin is a well-known therapeutic approach for numerous respiratory and gastrointestinal ailments (Araujo & Leon, 2001). According to Oriental beliefs, it has habitually been used in fighting abnormalities linked to inflammatory and peroxidative injury (Trujillo et al., 2013). Most of the biological actions of Curcuma longa L. are attributed to curcumin, which is suggested to be a top-ranked alternative in protecting against chemotherapy-associated disturbances as it reduces the production of apoptotic mediators and free radicals. The anti-apoptotic ability of curcumin is mediated by activating the DNA repair process (Chen et al., 2017), down-regulating the transcript levels of pro-apoptotic mediators, up-regulating those of anti-apoptotic mediators and inducing cytoprotective proteins (Ben Yehuda Dai et al., 2016; Greenwald et al., 2017). Neutralization of reactive oxygen species, up-regulation of enzymatic antioxidants expression and stimulation of the production of non-enzymatic ones (Barzegar & Moosavi-Movahedi, 2011; Lavoie et al., 2009) reflect the dual functional antioxidant role of curcumin. The above-mentioned multifaceted properties of curcumin offer a solid intellectuality for interfering with the different toxicological targets of DS.  Curcumin succeeded in restoring the typical histomorphometric features and reducing the apoptosis in the kidney. Curcumin might exert its renoprotective action through its cytoprotective, anti-apoptotic and antioxidant characteristics. The findings of this study shed light on using natural phytochemicals to alleviate the adverse influences of chemotherapies. . These outcomes are of utmost significance in opening windows toward incorporating curcumin in fighting the DS-related defects and touching a new ground for exploring its usefulness in combating the other dangerous effects of DS.

Beneficial effects of curcumin in the diabetic rat ovary: a stereological and biochemical study
Histochemistry and Cell Biology | December 2022
Curcumin treatment had a protective effect on the number of primordial follicles in the DC2 group and on antral follicle numbers in the DC3 group. Curcumin also exhibited positive effects on CAT activity and SOD levels, blood glucose levels, and corpus luteum, connective tissue, and blood vessel volumes in the DC2 and DC3 groups. Curcumin also ameliorated FSH levels in the DC1 and DC3 groups (p < 0.01). These findings suggest that curcumin exhibits protective effects on ovarian structures and folliculogenesis, especially when used concurrently with the development of diabetes or in later stages of the disease.

Old but Fancy: Curcumin in Ulcerative Colitis—Current Overview
Nutrients | December 2022
Over the last few years curcumin, a natural polyphenol belonging to the curcuminoid family (compounds derived from Curcuma longa L. [turmeric root]), is of greater interest in the context of managing UC. It seems that curcumin is a promising natural compound due to its widely described multi-beneficial effects on microbiota alteration and antioxidative, antitumor and—the most relevant—anti-inflammatory properties. Curcumin, also known as the ‘golden spice of India’, has been used for thousands of years as an essential medicinal, herbal ingredient that exhibits anti-inflammatory, antioxidant, or antimicrobial properties, mainly. It is also well-known in Chinese traditional medicine. Since 2020, the interest in curcumin for treating UC has increased noticeably, as evidenced by the increase in published systematic reviews. Searching via PubMed the descriptors “curcumin and ulcerative colitis” yielded sixteen systematic reviews and/or meta-analyses since 2012, where nine of them have been published from 2020 to the present. For some individuals affected by UC, there seems to be a real need to identify curcumin’s role as a supplement in safe, bioavailable, tolerated doses, and to incorporate it into routine clinical practice for better clinical outcomes and improvement of the quality of life of patients.

New Insights into Dose-Dependent Effects of Curcumin on ARPE-19 Cells
International Journal of Molecular Sciences | December 2022
Curcumin is a natural and biologically-active molecule that has been largely studied because of its versatility; indeed, there is a huge number of studies based on the use of curcumin in different pathological contexts, including ocular diseases. This compound has been shown to elicit antioxidant, anti-inflammatory, and anti-angiogenic effects in various cell systems. Curcumin is particularly important because of its versatility. Curcumin is the main curcuminoid extracted from the rhizome of Curcuma longa. Curcumin is considered a pleiotropic compound because of its ability to interact with many cellular components and influence a high number of cellular mechanisms. Altogether, our findings show new dose-dependent mechanisms of action of curcumin that suggest a wide therapeutic application in ocular diseases with different pathogenesis (i.e., proliferative vitreoretinopathy or Age-Related Macular Degeneration). This interpretation is in accordance with previous evidence about the cytotoxic effects of curcumin in particular conditions and contributes to underlining new insights into the effects of this very useful compound. Taken together our results agree with the high versatility of Curcumin for application in ophthalmic diseases. Administration of high concentrations of curcumin may be recommended to limit the progression of the disease. By contrast, a lower dosage of Cur should be used for ocular pathologies characterized by RPE degeneration, such as Age-related macular degeneration, to promote RPE health and survival. We also showed new dose-dependent effects of curcumin, highlighting mechanisms by which curcumin acts on RPE cells which lays the foundation for further studies in the field.

Curcumin: A Novel Way to Improve Quality of Life for Colorectal Cancer Patients?
International Journal of Molecular Sciences | December 2022
Several preclinical studies have demonstrated that curcumin acts through multiple cellular pathways and possesses both anti-cancer properties against CRC and the capacity to mitigate chemotherapy-related side effects and overcome drug resistance. In this review article, we suggest that the addition of curcumin to the standard chemotherapeutic treatment for metastatic CRC could reduce associated side-effects and overcome chemotherapy resistance, thereby improving patient QoL. For many years, curcumin (diferuloylmethane)—the “golden spice”—has been widely studied because of its pleiotropic effects in cancer. Curcumin, a hydrophobic polyphenol, is derived from the rhizome of the herb Curcuma longa and constitutes the major curcuminoid in the spice turmeric (77% curcumin, 17% demethoxycurcumin, 3% bis-demethoxycurcumin). Curcumin is “generally recognized as safe” (GRAS) as a dietary supplement by the U.S Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA) and has been catalogued with the E100 code of the European Union. One of the clinical benefits of curcumin is the improvement of Quality of Life in several health conditions, including cancer. Curcumin is a pleiotropic agent that acts through multiple cellular pathways and has been shown to possess anti-cancer properties against Colorectal Cancer in vitro and in vivo. Many of its anti-cancer properties have been attributed to its role as an anti-inflammatory and antioxidant, as well as to its ability to modulate the cell cycle and the pathways involved in proliferation, apoptosis, migration, invasion, angiogenesis, and metastasis, which are typically targeted by the drugs used to treat Colorectal Cancer. Mechanistically, curcumin modulates several Colorectal Cancer molecular targets at the same time—either by altering their gene expression, activation, or signaling pathways, or by direct interaction. Importantly, in addition to its well-known anti-cancer properties, curcumin can also alleviate some of the chemotherapy-related side effects. For example, curcumin attenuates the liver injury induced by oxaliplatin through activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling, a key regulator pathway of cellular defense against oxidative and electrophilic stresses, as well as the nerve damage and the oxidative damage to mitochondria caused by oxaliplatin. In fact, curcumin has been shown to not only hinder mitochondrial damage but also to protect mitochondria and induce activity of mitochondrial complex enzymes. Interestingly, similar effects of curcumin on cisplatin-related toxicity have been observed in several tumor types. Additionally, curcumin protects against irinotecan-induced intestinal injury by inhibiting nuclear factor kappa B (NF-κB). Recently, it has been shown that curcumin attenuates bevacizumab-associated cardiotoxicity by suppressing oxidative stress and preventing mitochondrial dysfunction in heart mitochondria. In a study of curcumin’s effects in cancer patients, Belcaro and colleagues looked at the side effects of chemotherapy in several tumor types, including colon, ovarian, lung, liver, kidney, and stomach cancers. Of 80 patients treated with chemotherapy, 40 simultaneously received 500 mg of curcumin. Chemotherapy-related nausea, diarrhea, constipation, weight loss, neutropenia, and cardiotoxicity were significantly lower in the patients receiving curcumin than in the control group. Moreover, patients receiving curcumin also required fewer medications for treating these side effects. In the same vein, turmeric supplementation for 21 days resulted in a clinically relevant and statistically significant improvement in global health status, symptom scores (fatigue, nausea, vomiting, pain, appetite loss, insomnia), and hematological parameters of breast cancer patients treated with paclitaxel. Taken together, these findings lead us to suggest that the addition of curcumin to the standard treatment of Colorectal Cancer could not only attenuate chemotherapy-associated side effects but also improve the QoL of patients. Most clinical data on curcumin come from early phase clinical trials, with results showing that oral curcumin can achieve efficacious levels in the colon with negligible distribution outside the gut. Moreover, curcumin was shown to be safe in advanced Colorectal Cancer patients when administered for up to four months. In addition, a study by James and colleagues found that curcumin at doses up to 2 gms daily was highly tolerable when added to a FOLFOX regimen in Colorectal Cancer patients with liver metastases. More recently, the same group performed a phase IIa randomized trial of first-line treatment for mCRC patients comparing FOLFOX +/−bevacizumab with the same regimen plus curcumin 2 gms/day (CUFOX) in mCRC patients. One of the most commonly used herbal supplements is curcumin, which has been extensively studied in cancer prevention and treatment. In fact, a plethora of preclinical studies have demonstrated the anti-cancer properties of curcumin as well as its role as a chemosensitizer agent. Several preclinical studies have demonstrated that the addition of curcumin to the standard treatment of Colorectal Cancer could decrease treatment-associated side effects and enhance chemotherapy efficacy. Therefore, considering that therapy-induced toxicity is among the most important factors limiting cancer treatment and is usually associated with discontinuation of potentially effective therapy, we suggest that adding curcumin, a natural compound with a very low toxicity profile in humans, to current Colorectal Cancer treatment regimens could be a potential synergistic strategy to reduce chemotherapy-related adverse effects, improve treatment efficacy, and decrease drug resistance.

The protective effects of curcumin on depression: Genes, transcription factors, and microRNAs involved
Journal of Affective Disorders | December 2022
Curcumin is one of the natural compounds that have been developed for depression therapy. Curcumin, the main therapeutic component of turmeric (Curcuma longa), has long been recognized for its significant anti-inflammatory and antioxidant properties due to its unique molecular structure (Duc et al., 2021; Nguyen and Kim, 2021; Nguyen et al., 2021c). Curcumin is well-known for its potential as a neuroprotective compound against depression. Curcumin has also been shown to possess physiological effects that are comparable to those of typical antidepressant medications (Ramaholimihaso et al., 2020). Curcumin may have an anti-depressant effect via the relevant genes. We also observed 74 miRNAs associated with depression that are targeted by curcumin, with hsa-miR-146a-5p having the greatest expression and interaction.  Curcumin's physicochemical characteristics and pharmacokinetics are consistent with its antidepressant effects due to its high gastrointestinal absorption, which did not remove it from the CNS, and its ability to penetrate the blood-brain barrier. Curcumin also inhibits CYP1A9 and CYP3A4. Our data mining found that curcumin's antidepressant effects were regulated by 14 different genes. The GeneMANIA prediction plug-in presented interaction types among the identified genes targeted by curcumin's possible benefits to counteract the development of depression. Converging evidence indicates that curcumin has been shown to exert modulating effects on neuroplasticity, insulin resistance, inflammatory pathways, excitotoxicity, neurotransmitter levels, nitrosative and oxidative stress, hypothalamic-pituitary-adrenal disturbances, and the endocannabinoid system, all of which can be implicated in the pathophysiology of depression (Ramaholimihaso et al., 2020).Our findings suggest that curcumin may have a possible anti-depressant impact via the following genes: ADORA2A, ALB, BDNF, FGF2, GLO1, GSK3B, IL6, MIF, NOS1, PTGS2, RELN, SELP, SOD1, and NR3C1.

Mechanism of apoptosis activation by Curcumin rescued mutant p53Y220C in human pancreatic cancer
Molecular Cell Research | December 2022
Based on our studies, it reflects that apoptosis in pancreatic cancer cells is mediated by curcumin-rescued mutant p53Y220C. In this study, we have shown through different biophysical and cell-based studies that curcumin binds and rescues mutp53Y220C to an active wild-type conformation and restores its apoptotic transcription function in BxPC-3-pancreatic cancer cells. In addition, the curcumin-rescued-p53Y220C (CRp53) showed significant hyperphosphorylation at Ser15, Ser20, and acetylation at Lys382 with an 8-fold increase in transcription activity in the BxPC-3 cell lines.

An in silico investigation on the interactions of curcumin and epigallocatechin-3-gallate with NLRP3 Inflammasome complex
Biomedicine & Pharmacotherapy | December 2022
The binding energies of curcumin and inhibitor MCC950 are almost identical.  Curcumin and EGCG, plant-derived compounds, inhibit the NLRP3-mediated IL-1β and IL-18 production.  Curcumin and epigallocatechin-3-gallate (EGCG) suppress the activation of the NLRP3 inflammasome. Our data showed that NLRP3 had a higher binding affinity for curcumin and EGCG than other complex proteins. The therapeutic effect of curcumin and EGCG may be due to the inhibition of inflammasome activation. The molecular and protein-protein interaction data indicated that the therapeutic effects of these two polyphenols are mediated by preventing the development of the NLRP3 complex.

MACC1-Dependent Antitumor Effect of Curcumin in Colorectal Cancer
Nutrients | November 2022
Curcumin is the curcuminoid compound of turmeric (Curcuma longa). Its remedial effect was shown for various diseases, such as Alzheimer’s and gastrointestinal disorders. Recent studies also demonstrated curcumin’s inhibitory impact on cancer progression and distant dissemination of tumors. Curcumin is able to inhibit proliferation and induces apoptosis. Further studies revealed that curcumin treatment enhances G1/S cell cycle arrest. Moreover, curcumin treatment induces autophagy through the suppression of the AKT/mTOR/p70S6K pathway. In addition to these, its effect on angiogenesis, cancer stemness, and NFκB signaling was reported in different tumor entities. Preliminary studies indicated the potential inhibitory effect of curcumin on prostate cancer metastasis by decreasing the expression of CXCL1 and 2. Curcumin reduced the metastasis-associated in colon cancer 1 expression, restricted the metastasis-associated in colon cancer 1-induced proliferation, and was able to reduce the metastasis-associated in colon cancer 1-induced cell motility as one of the crucial steps for the distant dissemination of the tumor. We further showed the metastasis-associated in colon cancer 1-dependent effect of curcumin on clonogenicity and wound healing. This study is, to our knowledge, the first identification of the effect of curcumin on the restriction of cancer motility, proliferation, and colony-forming ability by using metastasis-associated in colon cancer 1 as a target. Taken together, we illustrated the prominent inhibitory effect of curcumin on MACC1 expression and MACC1-induced phenotypes. In addition, we further revealed the MACC1-dependent anti-proliferative and anti-migratory effects of curcumin. Although the experiments have been conducted in the established cell lines, these promising results can expand in the other models so that curcumin can further supplement the treatment of CRC patients, notably those who cannot tolerate statins and have high MACC1 expression. This is the first study showing the effect of curcumin on reducing MACC1 expression in the established cell lines. In this study, we demonstrated the MACC1-dependent inhibitory effect of a wide range of curcumin concentrations on MACC1-induced viability, proliferation, migration, wound healing, and clonogenicity.

Effects of curcumin, a bioactive component of turmeric, on type 2 diabetes mellitus and its complications: an updated review
Food & Function | November 2022
Among the herbal supplements, turmeric (Curcuma longa L.) has been attracting an avalanche of attention owing to its main component, curcumin. This review examines the physiological activities and mechanisms of action of curcumin associated with type 2 diabetes and its complications. The anti-diabetic characteristic of curcumin is mainly attributed to its anti-inflammatory as well as anti-oxidant activities. In addition to these activities, curcumin has been developed as a promising prevention/treatment choice for diabetes complications by modulating various critical signal steps owing to the anti-hyperglycemic and anti-hyperlipidemic activities of curcumin. Studies on diabetic humans and animals have revealed that curcumin may have positive effects on oxidative stress and inflammation and may reduce fasting blood glucose levels, increase insulin sensitivity/secretion and regulate the lipid profile. Thus, it may prevent and treat diabetes by affecting various molecular targets.

Curcumin Represses Colorectal Cancer Cell Proliferation by Triggering Ferroptosis via PI3K/Akt/mTOR Signaling
Nutrition and Cancer  | November 2022
Curcumin is known to suppress the progression of colorectal cancer by inhibiting cancer cell proliferation. In this study, we explored the role of ferroptosis in the antiproliferative properties of curcumin. The effect of curcumin on ferroptosis In Vitro was evaluated in HCT-8 cells. Ferroptosis was first blocked by ferrostatin-1 and the antiproliferative effect of curcumin was evaluated by determining the levels of ferroptotic markers, including glutathione, SLC7A11, GPX4, iron, malondialdehyde, and reactive oxygen species. Curcumin repressed HCT-8 cell proliferation in a dose-dependent manner. Treating HCT-8 cells with curcumin significantly downregulated GSH, SLC7A11, and GPX4, while significantly increasing levels of iron, MDA, and ROS. In addition, curcumin promoted ferroptosis and reduced proliferation of HCT-8 cells by suppressing the PI3K/Akt/mTOR pathway, and these effects were antagonized by Fer-1. The effects of curcumin were antagonized by a PI3K agonist and reinforced by a PI3K inhibitor. Curcumin triggers ferroptosis and suppresses proliferation of colorectal cancer cells by inhibiting the PI3K/Akt/mTOR signaling pathway. These results indicate its potential as a treatment against colorectal cancer.

Neuroprotective Activities of Curcumin in Parkinson’s Disease: A Review of the Literature
International Journal of Molecular Sciences | November 2022
Curcumin is a neuroprotective agent with antioxidant, anti-inflammatory, free radical scavenging, mitochondrial protecting, and iron-chelating properties, which enhance DA levels in the brain.  Curcumin is a polyphenolic compound isolated from the rhizomes of Curcuma longa (turmeric). It has been demonstrated to have potent anti-inflammatory, antioxidant, free radical scavenging, mitochondrial protecting, and iron-chelating effects, and is considered a promising therapeutic and nutraceutical agent for the treatment of Parkinson’s disease. The interaction of curcumin with α7-nACh receptors provides further evidence for a potential neuroprotective role for curcumin in Parkinson’s disease. Additionally, curcumin and derivatives show a high safety profile with minimal reported toxicity as demonstrated both in in vitro and in in vivo studies in Parkinson’s disease models. Therefore, gaining a better understanding of the neuroprotective properties of curcumin could have significant therapeutic implications. The evidence reviewed supports curcumin’s powerful molecular and cellular effects in neurodegenerative disorders as an appealing strategy for improving Parkinson’s disease management and prognosis. Perkins and colleagues reported that humans require a daily dose of 1.6 g curcumin to achieve the desired results. Concomitant administration of piperine with curcumin significantly reduced elimination and half-life clearance of curcumin.

Schizophrenia, Curcumin and Minimizing Side Effects of Antipsychotic Drugs: Possible Mechanisms
Neurochemical Research | November 2022
Curcumin has important therapeutic properties such as antioxidant, anti-mutagenic, anti-inflammatory, and antimicrobial functions and protection of the nervous system. Also, the ability of curcumin to pass the blood-brain barrier raises new hopes for neuroprotection. Curcumin can improve and prevent further probable neurological and behavioral disorders in patients with schizophrenia. Alternative therapy such as curcumin can reduce the severity of symptoms without significant side effects. It decreases the side effects of neuroleptics and retains lipid homeostasis. Curcumin increases the level of brain-derived neurotrophic factor and improves hyperkinetic movement disorders. Curcumin may act as an added counteraction mechanism to retain cell integrity and defense against free radical injury. Thus it appears to have therapeutic potential for improvement of schizophrenia. In this study, we review several properties of curcumin and its ability to improve schizophrenia and minimize the side effects of antipsychotic drugs, and we explore the underlying mechanisms by which curcumin affects schizophrenia and its symptoms.

Glutathione Compared to Curcumin in the Management of Systemic Lupus Erythematosus: A Systematic Review
Cureus | November 2022
Curcumin can be a more promising alternative since it operates on various pathways and is a more easily accessible source. Based on the data available, curcumin shows a broader range of applications. It has actions on many more pathways. Hence, curcumin is a more apt drug for usage soon. Curcumin is a more available, naturally occurring compound. In addition, some studies also indicate the effect of curcumin on glutathione function. Curcumin also has more studies proving its role in the management of SLE, thus making it a safer bet for case management. The ability of curcumin to interact with several immunomodulatory pathways makes it so valuable for managing autoimmune diseases. The activation of oxidative pathways is how curcumin's anti-inflammatory role is activated. Curcumin targets the inhibitor of kappa-B kinase subunit beta (IKKβ) of the NFκB pathway to help reduce inflammation. NFκB downregulation by curcumin minimizes the release of nitric oxide, ILs, and various other inflammatory markers from the T cells. Curcumin also prevents neutrophil chemotaxis, thus reducing inflammatory responses in tissues. Curcumin acts by causing impairment in the formation of pro-inflammatory markers. Curcumin plays a role in adjusting the levels of inflammatory markers from cells. It reduced IL types 4, 6, and 8 and tumor necrosis factor (TNF) alpha. Reducing free radicals in the body helps reduce inflammatory changes in tissues.

Curcumin improves insulin sensitivity in high-fat diet-fed mice through gut microbiota
Nutrition & Metabolism | November 2022
Curcumin is a polyphenolic compound extracted from tropical plant Curcuma longa, and as a phytochemical derived from a medicinal and edible food, it not only has an extremely low level of toxicity but also has been used in traditional medicine to improve metabolic diseases. Moreover, curcumin has been shown to improve metabolic syndrome in basic research, and its potential efficacy in improving diabetes has also been demonstrated in clinical trials. Therefore, curcumin has excellent prospects for clinical application in the prevention and treatment of insulin resistance. In a recent study by our research team, gut microbiota were shown to mediate the enhancement of uncoupling protein 1-dependent thermogenesis by curcumin in high-fat diet-fed mice, while curcumin increased energy consumption by improving high-fat diet-induced gut microbiota dysbiosis and hence ameliorating high-fat diet-induced obesity in mice. Accordingly, we speculated that curcumin may exert its protective effects against insulin resistance via gut microbiota modulation. We believe this knowledge would provide a theoretical basis for the clinical application of curcumin in the prevention and treatment of metabolic syndrome and type 2 diabetes, as well as new ideas for the treatment of metabolic diseases. Curcumin-restructured fecal microbiota produced similar effects to curcumin, while also confirming that curcumin improved insulin sensitivity through gut microbiota modulation in high-fat diet-fed mice. This study demonstrated that curcumin ameliorated high-fat diet-induced GLMDs and increased insulin sensitivity, and verified that the beneficial effects of curcumin required its modulation on gut microbiota. Moreover, we found that curcumin upregulated the expression of the gut-derived hormone FGF15, and this upregulation was also dependent on gut microbiota. Our findings suggested that curcumin at least partly exert its effects on increasing insulin sensitivity via FGF15 upregulation in high-fat diet-fed mice. This study provided a theoretical basis for the clinical application of curcumin in the treatment of metabolic syndrome and type 2 diabetes. In addition, it is hoped that our findings will provide novel ideas on nutritional manipulations of gut microbiota for the treatment of metabolic diseases.

Curcumin and Its Analogs in Non-Small Cell Lung Cancer Treatment: Challenges and Expectations
Biomolecules | November 2022
Curcumin, a natural polyphenolic compound extracted from the root of turmeric, possesses diverse pharmacologic activities, including anti-diabetes, anti-aging, anti-Parkinson’s disease and Alzheimer’s disease, anti-cardiovascular disease, and anti-cancer, etc. Specifically, in tumor treatment, modern medicine has demonstrated that curcumin exerts therapeutic effects on various cancers, including breast cancer, colorectal neoplasm, liver carcinoma, glioblastoma, gastric tumor, and lung carcinoma, etc. We determined via a PubMed database search that researchers first reported assessing curcumin as an anticancer drug in 1985. Ten years later, investigators found that Cur could suppress lung tumor metastasis and extend the life span of mice. Since then, many non-small cell lung cancer (NSCLC) preclinical studies revealed that curcumin could inhibit tumor nodules ; restrain cancer stem cells; control the cell cycle; suppress immigration, invasion, and repair; induce the production of ROS and ER stress; trigger apoptosis; elevate DNA damage and ferroptosis; and promote necrotic cell death, thereby treating and preventing NSCLC. The broad actions through which curcumin can affect non-small cell lung cancer (NSCLC) in vitro and in vivo are summarized. Considerable preclinical evidence has revealed that curcumin and its analogs affect non-small cell lung cancer (NSCLC) via various mechanisms, such as inducing ROS production, increasing ferroptosis, changing mitochondrial potential, and disturbing cellular signaling pathways. Additionally, co-treatment with curcumin and other agents synergistically enhances cytotoxicity in non-small cell lung cancer (NSCLC) cells to suppress tumor cell growth, migration, and invasion. This evidence suggests that curcumin and its analogs offer promise to prevent non-small cell lung cancer (NSCLC) in humans.

Quinacrine and Curcumin in combination decreased the breast cancer angiogenesis by modulating ABCG2 via VEGF A
Journal of Cell Communication and Signaling | November 2022
Curcumin + QC inhibited the proliferation, invasion, migration and expression of representative markers of metastasis and angiogenesis. Curcumin + QC inhibited the ABCG2 expression and thus reduced the angiogenesis. Reduction of vascularization was also observed after treatment of Curcumin + QC.  Curcumin + QC inhibited the process by inhibiting ABCG2 in breast cancer.

Combination of curcumin and piperine synergistically improves pain-like behaviors in mouse models of pain with no potential CNS side effects
CM Journal | November 2022
For centuries, turmeric containing curcumin and Piper nigrum containing piperine have been used as food additives and folk medicine, including Traditional Chinese Medicine. The combination of C. longa curcumin, and P. nigrum piperine, has been used in traditional medicine.  Many recent studies reported synergistic effects of curcumin and piperine combination in various pharmacological models, including lung cancer, aging, and hepatocellular carcinoma.   Curcumin has also been reported as a potential analgesic both in animals and humans and exhibits diverse cellular and molecular targets. Curcumin inhibits pain neurotransmission by modulating immune and neuronal cells at cellular and mechanistic levels. In animal models of pain, curcumin suppresses pro-inflammatory mediators and increases endogenous anti-inflammatory mediators by modulating peripheral and central immune cells. The present study demonstrates strong antinociceptive synergism between curcumin and piperine in mouse models with no potential CNS side effects, suggesting its possible use in clinical trials.  The combination of curcumin and piperine produced synergistic interaction in the formalin, tail-flick, and cold plate tests. The synergistic interaction of curcumin and piperine was further confirmed by the efficacy of the combination in LPS-stimulated RAW 264.7 macrophage cells. Curcumin and piperine interacted synergistically, reducing proinflammatory mediators. The combination also demonstrated better compatibility profiles with neuronal cells.  The combination of curcumin and piperine synergistically ameliorates pain-like behaviors in the mouse formalin model. Curcumin and piperine significantly ameliorate formalin-induced peripheral and central inflammation. Curcumin and piperine synergistically attenuate inflammatory response in-vitro.  The curcumin-piperine combination at the highest dose exhibited significantly lesser expression of pro-inflammatory cytokines compared to the individual treatment at respective concentrations. Curcumin-piperine combination showed better compatibility with neuronal cells compared to individual treatments. The combination of curcumin and piperine synergistically interacts in suppressing pain-like behaviors induced by heat stimuli. The combination of curcumin and piperine synergistically interacts in suppressing pain-like behaviors by cold stimuli. Reduction in locomotive behaviors was not observed with the curcumin-piperine combination, indicating no potential CNS side effects of curcumin-piperine combination at its highest therapeutic doses.  Curcumin and piperine interacted synergistically, suppressing inflammatory mediators with favorable compatibility with neuronal cells. Curcumin and piperine have been shown to interact synergistically in various preclinical pharmacological studies. The combination of curcumin and piperine elicited a greater antinociceptive effect compared to that of either curcumin or piperine alone. The isobolographic analysis was performed to evaluate the type of interaction, wherein strong antinociceptive synergism between curcumin and piperine was found. This interaction produced by the combination of these two compounds could be due to their pharmacodynamic and pharmacokinetic interactions. Pharmacodynamically, the combination of curcumin and piperine could simultaneously inhibit multiple sites of action in the pain pathway. The ability of curcumin and piperine to modulate diverse pathways of pain could lead to robust inhibition of pain transmission when those are coadministered. Hence, the pharmacodynamic interaction between curcumin and piperine could be one of the potential reasons for the observed antinociceptive synergism in this study. In addition, it has also been proved that piperine can increase the delivery of curcumin to systemic circulation due to its ability to improve the pharmacokinetic profiles of curcumin. Piperine was reported to increase the bioavailability of oral curcumin: 154% and 2000% increase in curcumin concentration in the plasma was observed in rats and humans, respectively. The increased concentration of curcumin in the bloodstream is due to the ability of piperine to decrease the rate of metabolism of curcumin in the intestine and liver. In the intestine, piperine regulates membrane lipid dynamics and inhibits the intestinal metabolism of curcumin, leading to enhanced curcumin retention in the intestine. Furthermore, piperine reduces the rate of curcumin metabolism in the liver by hindering aryl hydrocarbon hydroxylation, ethylmorphine-N-demethylation, 7-ethoxycoumarin-O-deethylation, and 3-hydroxy-benzo(a)pyrene glucuronidation and glucuronidation, which subsequently reduce the first-pass metabolism of curcumin. Hence, coadministration of piperine and curcumin enhances the oral bioavailability of curcumin, and thereby, its therapeutic efficacy. This factor may also have influenced the strong antinociceptive synergism observed in this study. Cells treated with the curcumin-piperine combination at their EC90 concentration showed no toxicity to neuronal cells. We found no effects of the individual curcumin and combination on the spontaneous locomotor activity at their high doses, while individual piperine reduced locomotor activity. The results indicate no potential CNS side effects of the curcumin and piperine combination.

Curcumin Sensitizes 4T1 Murine Breast Cancer Cells to Cisplatin
In Vivo | November 2022
Curcumin, which is highly effective at inducing cell death in various types of cancer, is a polyphenolic yellow pigment derived from Curcuma longa. It can selectively chemosensitize tumor cells, thereby protecting normal cells from chemotherapy and radiotherapy. In this study, treatment of mice with curcumin led to a decrease in tumor mass. Treatment with curcumin followed by cisplatin led to complete tumor mass regression in mice compared with the control group. Zhao et al. reported that high levels of PAR4 in the serum and plasma of mice inhibited the growth of metastatic lung tumor nodules derived from Lewis lung carcinoma cells in syngeneic mice. Curcumin is a good inducer of PAR4 expression in breast cancer cells and a secretagogue in non-tumor cells in vivo. In addition, it sensitizes cells to the effect of cisplatin; hence, curcumin, alone or in combination with chemotherapy, might be used as an alternative treatment for breast cancer.

Curcumin Prevents Diabetic Osteoporosis through Promoting Osteogenesis and Angiogenesis Coupling via NF-κB Signaling
Evidence-Based Complementary and Alternative Medicine | November 2022
Curcumin, an effective component extracted from Curcuma longa, exhibits antioxidation, regulation of bone metabolism and hypoglycemic effects. Treatment prevented bone loss and promoted vessel formation in diabetic osteoporosis mice. Based on these results, we concluded that curcumin ameliorated diabetic osteoporosis.. Reports demonstrate that curcumin may ameliorate bone microarchitecture and enhance BMD in APP/PS1 transgenic mice and has shown bone protective effect on postmenopausal osteoporosis animal models and patients. More importantly, recent studies have found the therapeutic value of curcumin on osteoporosis induced by diabetes. The benefits of curcumin on bone formation and regeneration are attributed to its capacity to reduce H2O2-stimulated osteoblast apoptosis, improving osteoblast mitochondrial function, and recovering the high glucose-impaired osteogenic differentiation of osteoblast and BMSCs. To our knowledge, this is the first to confirm that curcumin prevents diabetes-induced bone loss by promoting BMSC-mediated osteogenesis and angiogenesis coupling. In this study, our results showed that curcumin treatment rescued high glucose-inhibited osteogenic differentiation ability of BMSCs in vitro. Furthermore, our in vivo results also revealed that curcumin prevented bone loss in diabetic mice. Our findings reveal the effects of curcumin in promoting the BMSCs-mediated osteogenesis and angiogenesis coupling in high glucose conditions. These impacts are preliminarily considered to be via NF-κB signaling pathway inhibition. Furthermore, curcumin may become a potential drug to prevent and treat diabetic osteoporosis through promoting bone regeneration and vessel formation.

In patients with osteoarthritis, is curcumin, compared to placebo, effective in reducing pain?
Journal of the Oklahoma State Medical Association | November 2022
Yes. Studies have shown that curcumin extract has benefit in treating osteoarthritic pain, compared to placebo. It is reasonable to use curcumin in addition to traditional osteoarthritis treatments, as studies show it has a low side effect profile. Curcumin is a bright yellow powder derived from turmeric, and has been used for centuries in alternative medicine for its anti-inflammatory properties. Subjects took 500 mg of curcimin plus 5 mg piperine extract (to enhance bioavailability) three times daily for 6 weeks.  WOMAC scores for patients taking curcumin averaged 37, while those taking placebo averaged 57. Results from this literature review suggest that curcumin can be considered by physicians as an adjunctive therapy to traditional therapies for osteoarthritis, as it does appear to offer benefit in pain relief compared to placebo. Although more evidence is needed to support curcumin as a replacement for NSAIDs or other mainstay therapies, the results of the studies reviewed are promising. Larger trials to investigate the efficacy of curcumin compared to NSAIDs would be appropriate. However, curcumin appears to be a safe and effective addition to osteoarthritis treatments for patients, and should not be overlooked by physicians.

Curcumin protects retinal neuronal cells against oxidative stress-induced damage by regulating mitochondrial dynamics
Experimental Eye Research | November 2022
Data indicate that curcumin protects against oxidative stress-induced injury in retinal neuronal cells by promoting mitochondrial fusion. Curcumin has anti-inflammatory, antimutagenic and antimicrobial properties, and has been administrated for asthma, diabetes and cancer in traditional medicine for a long history (Nabavi et al., 2015; Qadir et al., 2016; Shahid et al., 2019). Curcumin has been found to regulate the apoptosis, proliferation, transformation and metastasis of cancer cells by inhibiting NF-κB signaling (Aggarwal et al., 2006). Curcumin also exerts its anti-inflammatory function via downregulation of COX-2, PGE-2 and proinflammatory factors including IL-1, 6, 8 and TNF-α or upregulation of peroxisome proliferator-activated receptor-γ (Michalik et al., 2006; Taylor and Leonard, 2011). In addition, several studies indicate that curcumin also shows therapeutic effect on several retinal diseases including primary retinitis, age-related macular degeneration, diabetic retinopathy and glaucoma (Nebbioso et al., 2021). Pretreatment with curcumin effectively attenuated H2O2-induced mitochondrial fission, and inhibited the intracellular ROS generation, mitochondrial membrane potential disruption, PINK1 expression, caspase-3 cleavage and apoptosis in R28 cells. Notably, knockdown of mitochondrial fusion protein Mfn2 dramatically attenuated curcumin's protection against H2O2-induced growth inhibition in R28 cells. In conclusion, our results indicate that mitochondrial fusion plays a vital role in curcumin-mediated protection against oxidative stress-induced retinal neuronal damage, and also suggesting mitochondria as a crucial target for the protection of neurons.

Effects of curcumin-piperine supplementation on systemic immunity in young women with premenstrual syndrome and dysmenorrhea: A randomized clinical trial
European Journal of Obstetrics, Gynecology, Reproductive Biology | November 2022
Curcumin decreased the serum immunoglobulin E (IgE) levels in women with premenstrual syndrome and dysmenorrhea. Curcumin + piperine treatment was associated with a significant reduction in the mean serum levels of  immunoglobulin E (IgE). Curcumin plus piperine might have positive effect on serum immunoglobulin E (IgE) levels with no significant changes on serum IL-10 and IL-12 in healthy young women with PMS and PD. Studies with higher doses and longer durations of treatment with curcumin are required to confirm these findings.

Alzheimer’s disease large-scale gene expression portrait identifies exercise and curcumin as top theoretical treatments
Scientific Reports | October 2022
For the Alzheimer’s disease portrait, the top three scoring treatments for reversing Alzheimer’s disease expression with little effect on exacerbating Alzheimer’s disease expression were for exercise. Overall, the ranking of treatments was similar for male and female portrait, although in males, curcumin was the second highest ranked treatment.

Isolation and In silico Study of Curcumin from Curcuma longa and Its Anti-Diabetic Activity
Applied Biochemistry and Biotechnology | October2022
The development of new drugs from natural products is still challenging, and the most extensively studied plant material is turmeric, Curcuma longa, which is the chief source of curcumin. Curcumin is a bright yellow solid. Based on the findings, it can be said that curcumin, a natural substance, has good therapeutic qualities when it is isolated.

The Pharmacological Mechanism of Curcumin against Drug Resistance in Non-Small Cell Lung Cancer
Evidence-Based Complementary and Alternative Medicine | October 2022
Curcumin is commonly utilized for the treatment of various cancers (e.g., breast cancer and hematological cancers). It has been found to have anticancer activity in  non-small cell lung cancer. Increasing evidence showed that curcumin could enhance immune function via various mechanisms. It was revealed that curcumin could enhance tumor antigen-specific T-cell induction in cancer cells. Curcumin inhibited CSN5 expression in cancer cells and sensitized them to anti-CTLA4 therapy. Additionally, curcumin could reverse resistance to targeted medicines. Curcumin overcomes primary gefitinib resistance in  non-small cell lung cancercells by causing cell death related to autophagy. Curcumin enhances gefitinib’s sensitivity by inhibiting cell proliferation and suppressing clonogenic capacity in NCI-H1975 cells. Curcumin can also enhance the effect of chemotherapy drugs. A previous study demonstrated that curcumin and doxorubicin work together more effectively in treating Hodgkin lymphoma. Curcumin in combination with immunotherapy, chemotherapy, or targeted drugs has the potential to be effective for drug-resistant non-small cell lung cancer.  Curcumin regulates drug sensitivity in non-small cell lung cancerby interacting with cell cycle, NF-kappa B, MAPK, Th17 cell differentiation signaling pathways, etc. The findings of our study reveal the relevant key signaling pathways and targets of curcumin as an adjuvant therapy in the treatment of non-small cell lung cancer, thus providing pharmacological evidence for further experimental research.

Antitoxic Effects of Curcumin against Obesity-Induced Multi-Organs’ Biochemical and Histopathological Abnormalities in an Animal Model
Evidence-Based Complementary and Alternative Medicine | October 2022
Curcumin exerted potent antitoxic, antioxidant, tissue-protective, and antiobesity effects. Curcumin is recommended to be added to various dietary regimens to prevent or delay the organs’ dysfunction among obese people. The most significant phenolic ingredient in turmeric is called curcumin, and it is yellow in color and is a natural phenolic antioxidant. Due to its biological and pharmacological characteristics, which include antioxidant and anti-inflammatory features, curcumin has received a lot of interest in various research studies, including human or experimental animal models in various diseases, including obesity. Genetic analyses of the related inflammatory signaling pathways (via assessments of adipose tissue expressions of TLR4, IL-6, and TNF-α) were performed to explore the potential mechanistic benefits of curcumin in reversing these metabolic abnormalities. Coadministration of curcumin with a high-fat diet group exhibited significantly decreased serum insulin and glucose levels when compared with the high-fat diet group. In parallel with our results, Hartogh et al. reported that by lowering the harmful effects of liver fat and increasing cell sensitivity to insulin, curcumin can lower blood glucose levels in obese rats. The present results could be attributed to the ability of curcumin to reduce oxidative stress and inflammatory response which contributed to insulin resistance. Similarly, curcumin treatment attenuated glucose intolerance and boost insulin sensitizing response.  Furthermore, curcumin administration caused strong induction of the antioxidant defenses, since SOD, CAT, and GSH-Px activities were significantly increased, reaching values similar to those of the control group. Curcumin’s effects may act by either directly scavenging the reactive oxygen metabolites or due to the presence of various antioxidant principles such as flavonoids, steroids, tannins, glycosides, triterpenoids, and polyphenolic compounds. The anti-inflammatory effects of curcumin form the basis of its potential clinical applications. In the present study, curcumin significantly reduces the inflammation state in high-fat diet group. Curcumin is an excellent antioxidant agent and has an effective role in the regression of DNA damage. Interestingly, the current study demonstrated that administration of curcumin to the high-fat diet group provided protection against hepatic disorders, duodenal and myocardial histopathological changes as confirmed by these results are in line with those of many researchers who found a marked reduction in steatosis of hepatocytes and an improvement in liver histopathology. It is likely to postulate that the antioxidative property of curcumin is the key to its therapeutic effect on gastrointestinal injury as documented by many researchers. Moreover, Gorabi et al. revealed that high-fat diet plus curcumin showed no histopathological changes in the myocardial structure, indicating a preventive effect of curcumin against histological cardiac changes induced by a high-fat diet. There is no doubt that the use of curcumin improved the histological findings as well as modulated metabolic and oxidative stress markers, as well as downregulated inflammatory biomarkers and apoptosis. Therefore, it is advised that curcumin be evaluated as a possible supplemental therapy for metabolic diseases linked to obesity brought on by high-fat diet.

Curcumin strengthens immunity by helping the generation of immune cells such as T cells and B cells
International Curry and Spices Symposium | October 2022
Immune cells such as B cells increased significantly in the lymph glands of rats administered with curcumin. Curcumin helps to produce antibodies and can contribute to the prevention of various infectious diseases such as the flu and colds and cancer. Curcumin is a yellow pigment component of turmeric, the main ingredient in curry, and is known to have excellent antioxidant and anti-inflammatory effects. Curcumin in turmeric has anti-cancer, anti-inflammatory, and antioxidant effects by inhibiting the activity of inflammation-related genes.

Roles of Curcumin on Cognitive Impairment Induced by a Mixture of Heavy Metals
Neurotoxicity Research | October 2022
The most important pathways involved in curcumin's protective activity against heavy metals were categorized as "regulation of neuron apoptotic process” and "negative regulation of apoptotic signaling route”. Curcumin was also well-positioned inside the CASP3 binding region. Three key miRNAs linked to cognitive impairment, mixed heavy metals, and curcumin were observed. These miRNAs were found to be related to the important pathways related to cognitive impairment and involved in curcumin's protective activity against mixed heavy metals such as "apoptosis multiple species”, “apoptosis”, and “Alzheimer’s disease”. Curcumin's physicochemical characteristics and pharmacokinetics are consistent with its therapeutic benefits in cognitive impairment, owing to its high gastrointestinal absorption and ability to cross the blood–brain barrier. Our findings emphasize the protective effects of curcumin in cognitive impairment caused by heavy metal mixtures and pave the way for molecular mechanisms involved in cognitive impairment pathology.

Protective effects of curcumin against traumatic brain injury
Biomedicine & Pharmacotherapy | October 2022
Curcumin has a broad range of clinical properties due to its considerable antioxidative and anti-inflammatory actions. This review discusses the pleiotropic mechanisms, the side effects, curcumin's delivery to the central nervous system (CNS), and its immunomodulatory and protective effects on  traumatic brain injury. Clinical trials, in vivo, and in vitro studies were extracted from different scientific databases, including PubMed, Scopus, and Google Scholar, to assess the effects of curcumin or its derivatives in  traumatic brain injury. Findings reveal that curcumin exhibited some protective effects on  traumatic brain injury via modulation of cell signaling pathways including toll-like receptor-4 (TLR-4), nuclear factor kappa B (NF-κB), and Nod-like receptor family proteins (NLRPs). Moreover, curcumin upregulates the brain-derived Neurotrophic Factor/Tropomyosin receptor kinase B (BDNF/TrkB) signaling pathway, phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT), nuclear factor erythroid 2-related factor 2 (Nrf2), which have crucial functions in modulation of TBI pathophysiological-mediated pathways. Curcumin displays beneficial immunomodulatory functions and protective capacities in different  traumatic brain injury models
.

Curcumin: An overview
Journal of Medicinal Plants Studies | October 2022
Curcumin is the active ingredient in the herbal remedy and dietary spice turmeric, having a wide range of therapeutic properties that covers antimicrobial, immune-health, multiple myeloma and cancers of various categories. Curcumin has been shown to exhibit antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal, and anticancer activities and thus has a potential against various malignant diseases, diabetes, allergies, arthritis, Alzheimer's disease, and other chronic illnesses. Curcumin inhibits the growth of Helicobacter pylori, which causes gastric ulcers and has been linked with gastric cancers.  Extracts of turmeric and its curcumin component exhibit strong antioxidant activity comparable to vitamins C & E. Several studies have demonstrated curcumin's ability to reduce oxidative stress. It appears that curcumin's role as an antioxidant may be due in part to its ability to down regulate nitric oxide formation. It has been proved already that curcumin down -regulates NF- kappaB in human multiple myeloma cells, leading to the suppression of proliferation and induction of apoptosis, thus providing the molecular basis for the treatment of multiple myeloma with this pharmacologically safe agent. Pharmacological studies have demonstrated that curcumin from Curcuma longa is an anti-mutagen as well as an anti-promotor for cancer.

The Role of Phytochemicals in the Treatment of Colorectal Cancer
Onco Therapeutics | October 2022
Phytochemicals like curcumin are naturally occurring and are known to exhibit anti-cancer activity against colorectal cancer by regulating various key signaling pathways including the Wnt/β-catenin signaling pathway. By regulating vital molecular pathways, the course of colorectal cancer can be positively altered. The evidence outlined within this literature review suggests the significance of these phytochemicals as preventive agents and their potential role in developing effective therapies. This review emphasizes the molecular mechanisms of curcumin, resveratrol, and sulforaphane that can effectively target colorectal cancer development and progression.

Review On Curcuma Longa Effect On Human Health
Journal of Emerging Technologies and Innovative Research | September 2022
Curcumin is the phytochemical derived from the bulb of the plant Curcuma longa and is the major component of turmeric. The herb has been used for thousands of years. It aids in the management of oxidative and inflammatory conditions, metabolic syndrome, arthritis, It may also help in the management of exercise-induced inflammation and muscle soreness, thus enhancing recovery and performance in active people. Most of these benefits can be attributed to its antioxidant and anti-inflammatory effects. Curcumin from the herb turmeric has been used for thousands of years. It aids in the management of oxidative and inflammatory conditions, metabolic syndrome, arthritis, It may also help in the management of exercise-induced inflammation and muscle soreness, thus enhancing recovery and performance in active people. Most of these benefits can be attributed to its antioxidant and anti- inflammatory effects. It has also demonstrated hepatoprotective, nephroprotective, neuroprotective, and cardioprotective properties. These characteristics provide the foundation for its therapeutic uses and the rationale for clinical trials. Many other medicinal and pharmacological properties of curcumin used for humans. In Ayurveda, curcumin has been used for various medicinal conditions including rhinitis, wound healing, common cold, skin infections, liver and urinary tract diseases. Curcumin was found to be effective even when given by different routes including topical, oral or by inhalation, dependent on the intended use.

Curcumin Targeting Non-Coding RNAs in Colorectal Cancer: Therapeutic and Biomarker Implications
Biomolecules | September 2022
Curcumin has shown potent anti-tumor and anti-inflammatory effects and is considered a hot spot in the research and development of anti-tumor drugs due to its advantages of precise efficacy, lower toxic side effects, and less drug resistance. Recent studies have revealed that curcumin has anti-tumor effects exerted on the epigenetic regulation of tumor-promoting/tumor-suppressing gene expression through the alteration of expression levels of non-coding RNAs. Curcumin has been approved as a food additive by the World Health Organization and the US Food and Drug Administration and has been listed as a third-generation cancer chemoprevention drug by the National Cancer Institute of the United States due to its safety, non-toxicity, and lack of adverse effects. Curcumin has a non-toxic chemical composition; almost all types of tumor markers can be regulated by it to exert an anti-tumor effect; undoubtedly, this provides a strong theoretical basis for cancer treatment. Studies have shown that curcumin could exert an anti-tumor effect both in vitro and in vivo through different mechanisms, including inhibiting the invasion, metastasis, and proliferation of tumor cells, inducing tumor cell apoptosis and autophagy, and resisting chemotherapy resistance. Recent studies have shown that curcumin is widely used as an anti-tumor agent because it regulates ncRNAs based on an epigenetic regulation mechanism; there are benefits to using curcumin in the treatment of colorectal cancer. Its anti-colorectal cancer effect is essentially through the indirect regulation of target genes or signaling pathways. In summary, these findings could provide favorable evidence for exploring the role of curcumin in the treatment of colorectal cancer via non-coding RNAs, which may provide new directions for the treatment and prognosis of colorectal cancer patients. Curcumin could affect the development of colorectal cancer by targeting oncogenes or tumor-suppressor genes; its anti-colorectal cancer effect is essentially through the indirect regulation of target genes or signaling pathways. Treated by curcumin, Lnc NBR2, Lnc KCNQ1OT1, Lnc PANDAR, and Lnc CCAT1 could prove to be potentially effective target molecules in the treatment progress of colorectal cancer.  In summary, these findings could provide favorable evidence for exploring the role of curcumin in the treatment of colorectal cancer via non-coding RNAs, which may provide new directions for the treatment and prognosis of colorectal cancer patients. Non-coding RNAs can be potential therapeutic targets for the occurrence and development of colorectal cancer, and curcumin-targeted non-coding RNAs have good biomarker and reference significance for the treatment of colorectal cancer.

The effect of eight weeks of Pilates with curcumin supplementation on liver enzymes and lipid profile in overweight and obese women
Obesity Medicine | September 2022
Curcumin supplement significantly improve liver enzymes. Pilates training plus Curcumin supplement significantly decreased anthropometry indices. Pilates and Curcumin alone or in combination led to significant changes in lipid profile. The results showed that weight, BMI, WHR and PBF decreased in the curcumin + Pilates group compared to the other groups. According to the results, an 8-week Pilates and curcumin alone or in combination reduced serum ALT, LDL-C, TG and T-Chol compared with the control group. Also, serum AST levels decreased from 23.75 ± 2.14 to 19.37 ± 1.98 in the curcumin group. Eight weeks of intervention with Pilates and curcumin alone or in combination seemed effective in improving lipid profile and reducing ALT enzyme levels in overweight and obese females. It also appears that the AST enzyme is only affected by curcumin supplementation.

Curcumin in the treatment of urological cancers: Therapeutic targets, challenges and prospects
Life Sciences | September 2022
Curcumin has been widely used in cancer treatment due to its ability to trigger cell death and suppress metastasis. The beneficial effects of curcumin in the treatment of urological cancers is the focus of current review. Curcumin can induce apoptosis in the three types of urological cancers limiting their proliferative potential. Furthermore, curcumin can suppress invasion of urological cancers through EMT inhibition. Notably, curcumin decreases the expression of MMPs, therefore interfering with urological cancer metastasis. When used in combination with chemotherapy agents, curcumin displays synergistic effects in suppressing cancer progression. It can also be used as a chemosensitizer. Based on pre-clinical studies, curcumin administration is beneficial in the treatment of urological cancers and future clinical applications might be considered upon solving problems related to the poor bioavailability of the compound.

The effects of curcumin in learning and memory impairment associated with hypothyroidism in juvenile rats: the role of nitric oxide, oxidative stress, and brain-derived neurotrophic factor
Behavioural Pharmacology | September 2022
Curcumin enhanced the performance of the rats in both MWM and PA tests. In addition, curcumin reduced malondialdehyde concentration and NO metabolites; however, it increased thiol content as well as the activity of catalase and superoxide dismutase enzymes in both the cortex and hippocampus. Curcumin also increased hippocampal synthesis of BDNF in hypothyroid rats. The beneficial effects of curcumin cognitive function in juvenile hypothyroid rats might be attributed to its protective effect against oxidative stress and potentiation of BDNF production.

Curcumin Modulates Oxidative Stress, Fibrosis, and Apoptosis in Drug-Resistant Cancer Cell Lines
Life | September 2022
The present study shows that curcumin induces anticancer activity against resistant cancer cell lines in a concentration and time-dependent manner. The protective activities of curcumin against the growth of cancer cells are mediated by modulating oxidative stress, regulating fibrosis, SIRT1 activation, and inducing cellular apoptosis. The bio-functional properties of curcumin and its derivatives - such as anti-tumor, antioxidant, and anti-inflammatory activities - have gained much attention in combating many human diseases, particularly cancer. Curcumin’s natural phenolic, hydrophobic, and antioxidant properties help it to diffuse through cancer cell membranes into the mitochondria, endoplasmic reticulum, and nucleus to perform chemo-preventive, antimetastatic, and anti-angiogenic actions. Curcumin has been reported to exert its chemotherapeutic efficacy through targeting several molecular pathways involved in mutagenesis, cell cycle regulation, tumorigenesis, apoptosis, and metastasis. Moreover, several studies showed that curcumin significantly reduces fibrosis via suppressing the overproduction of collagen-linked factors such as hydroxyproline, fibronectin, and TGF-β1 in cancer cells. In breast cancer, curcumin is shown to suppress the spread of cancer cells to other parts of the body. In addition, curcumin regulates different signaling pathways, especially breast cancer gene. In colon cancer, curcumin induces FADD (Fas-Associated Protein With Death Domain), triggering apoptosis. Moreover, it inhibits colon cancer metastasis. Similarly, in lung cancer, curcumin modulates the circ-PRKCA/miR-384/ITGB1 pathway, suppressing the malignancy of lung carcinoma. It also reduces migration and invasion of lung carcinoma. Curcumin has been reported to sensitize tumor cells to chemotherapeutic drugs and ionizing radiation therapy. In conclusion, curcumin induces anticancer activity against sensitive and drug-resistant cancer cells in a concentration- and time-dependent manner. The protective activities of curcumin against the growth of cancer cells are mediated by modulating oxidative stress, regulating fibrosis, SIRT1 activation, and inducing cellular apoptosis. Therefore, curcumin could be tested as an auxiliary therapeutic agent for current treatments to improve the prognosis in patients with drug-resistant cancer.

Curcumin as adjuvant treatment in patients with non-alcoholic fatty liver (NAFLD) disease: A systematic review and meta-analysis
Complementary Therapies in Medicine | September 2022
Curcumin has been shown to improve non-alcoholic fatty liver disease’s severity and increase liver steatosis resolution compared to the placebo groups. Curcumin was also found to reduce triglycerides if taken more than eight weeks’ duration.  There is no major side effect, and our findings showed no difference in the adverse effect. Curcumin is acknowledged as a powerful antioxidant and anti-inflammatory agent. A review reported that the consumption of curcumin significantly reduced liver enzymes, decreased low-density lipoprotein and total cholesterol among non-alcoholic fatty liver disease patients. Another review found curcumin showed significant effects on fasting blood sugar, insulin level, and homeostasis model of assessment insulin resistance among women with polycystic ovary syndrome. Curcumin is anticipated to function as antiviral drugs to treat the current COVID-19 virus based on in vitro and in vivo studies as it showed high inhibitory activity towards the virus. Goodarzi and Jalali found that curcumin reduced liver enzymes in non-alcoholic fatty liver disease compared to the placebo group, which is similar to our findings. Mansour-Ghanaei and Wei showed that curcumin reduced aspartate aminotransferase. Our finding is similar to Jalali that curcumin reduced total cholesterol in participants compared to the placebo group. Wei and Jalali showed that curcumin reduced the low-density lipoprotein compared to the placebo group. Wei also showed that curcumin reduces triglycerides compared to the placebo group. Curcumin reduced BMI in participants with the non-alcoholic fatty liver disease compared to the placebo group. Besides improving the liver ultrasonographic findings, curcumin also reduced serum liver enzymes, total cholesterol, and BMI. There is no major side effect, and our findings showed no difference in the adverse effect between the two groups. Our meta-analysis shows that curcumin has favorable effect on liver ultrasonographic findings, reduced serum liver enzymes, total cholesterol, and BMI in participants with non-alcoholic fatty liver disease. Therefore, promoting curcumin as an adjuvant treatment on NAFLD patients might be justified.

Prevention of Female Reproductive Disorders with the Help of Curcumin
Journal of Antimicrobial Agents | September 2022
Various examinations on Curcumin have exhibited its many advantages because of its cell reinforcement, hostile to disease, against joint inflammation, against asthmatic, against microbial, against viral and against parasitic properties. Curcumin shows huge cancer prevention agent properties by breaking the chain response of free extreme creation. Likewise, curcumin diminished the protein reactions engaged with aggravation processes, for example, those of cancer rot factor alpha, interleukin-1, IL-2, IL-6, IL-8 and IL-12.  Curcumin has been displayed to hinder the actuation of TNF-α in the NF-κB pathway and kill the receptive oxygen species, causing oxidative pressure. As oxidative pressure and irritation are in most persistent sicknesses, curcumin supplementation could altogether offer different medical advantages. Coorganization of curcumin with piperine, an alkaloid in dark pepper, improves curcumin's bioavailability by up to 2000 percent.

Anti-migratory effect of curcumin on A-549 lung cancer cells
Hormone Molecular Biology and Clinical Investigation | September 2022
Curcumin inhibited lung cancer cells through various molecular pathways. RECK/MMPs axis as a regulator of cancer cell migration was modulated after curcumin treatment and invasion of lung cancer cells was decreased. The results of MTT assay showed that the cytotoxic effect of curcumin was in a dose dependent manner. Flow cytometry results demonstrated a significant increase in the percentage of apoptotic cells in curcumin treated group. In addition, curcumin inhibited migration rate in lung cancer cells.

A network pharmacology approach to identify the mechanisms and molecular targets of curcumin against Alzheimer's disease
Medicine | September 2022
Curcumin and its metabolites possess anti-inflammatory, antioxidant, antimicrobial, and antiviral activities. Further, in recent years, the literature reports that curcumin has beneficial effects in diseases of the neurological system, including Alzheimer's disease. Curcumin suppresses the formation and promotes the disaggregation of amyloid-β plaques, attenuates the hyperphosphorylation of tau, and enhances its clearance. available studies indicate that curcumin has been widely used in neurodegenerative diseases. A recent study indicated that curcumin could improve lipid metabolic disorders by the ATP binding cassette A1 transmembrane transport system in Alzheimer's disease. In addition, curcumin improves parkinsonian disability scores in vivo and inhibits PC12 cell death in vitro by inhibiting AKT/mTOR signaling pathway, which is mediated by autophagy. As valuable targets for Alzheimer's disease treatment, curcumin can systematically improve the pathological features of stroke through multifactorial, multitarget, and multipathway. In summary, curcumin has the potential to be more effective than current treatments.

Curcumin as a novel approach in improving lipid profile: An umbrella meta-analysis
Nutrition, Metabolism and Cardiovascular Diseases | September 2022
Curcumin supplementation significantly reduced serum levels of LDL-cholesterol, triglycerides and total cholesterol. Curcumin intake significantly increased high-density lipoprotein cholesterol (HDL-cholesterol) levels. Curcumin has ameliorating effects on triglycerides, total cholesterol, LDL-c, and HDL-c levels. Overall, curcumin could be recommended as an adjuvant anti-hyperlipidemic agent. We showed that curcumin supplementation could be effective for lipid profile.

Antitumor effect of infrared whole-body hyperthermia with curcumin in breast cancer
Medical Applications | September 2022
Curcumin has traditionally been used as a food additive or as a remedy in traditional medicine for its anticancer and non-toxic effects. Thus, this research proposed the combination of curcumin and IHT as an alternative to chemotherapy in breast cancer treatment. Results showed that tumor growth inhibition and body weight gain in the combination treatment group are significantly different compared to control. The group also had the longest median survival time (42 days) with no mortality observed during the experiment. This result indicates that the combination treatment is well tolerated by the mice and has negligible levels of toxicity. Platelet to Lymphocyte Ratio) and Neutrophils to Lymphocytes Ratio results indicate that the combination treatment has better prognosis outcome than single treatment and may become a potential alternative antitumor treatment of breast cancer.

Synergistic anticancer effects of curcumin and crocin on human colorectal cancer cells
Molecular Biology Reports | September 2022
Curcumin, a polyphenol compound derived from the Curcuma longa L, and crocin, a hydrophilic carotenoid from Crocus Sativus Linnaeus, are traditionally used in food preparations in many countries and could act as chemopreventive compounds against several diseases, including cancer.  Based on the obtained results, curcumin and crocin treatment could cooperatively reduce cell viability and induce apoptosis in SW-480 cells by modulating the expression of Bax, Bcl-2, Caspase-3, Caspase-8, Caspase-9, Jak2, Stat3, and Akt1 genes. Besides, curcumin and crocin were able to synergistically increase the cell cycle arrest at the sub G1 phase, induce autophagy and decrease the clonogenic ability of SW-480 cells. These results suggested that curcumin and crocin combination could be considered a more effective therapeutic strategy for inhibiting colorectal cancer.

Curcumin against gastrointestinal cancer: A review of the pharmacological mechanisms underlying its antitumor activity
Frontiers in Pharmacology | September 2022
Gastrointestinal cancer poses a serious threat to human health globally. Curcumin, a hydrophobic polyphenol extracted from the rhizome of Curcuma longa, has shown reliable anticancer function and low toxicity, thereby offering broad research prospects. Numerous studies have demonstrated the pharmacological mechanisms underlying the effectiveness of curcumin against GIC, including the induction of apoptosis and autophagy, arrest of the cell cycle, inhibition of the epithelial–mesenchymal transition processes, inhibition of cell invasion and migration, regulation of multiple signaling pathways, sensitization to chemotherapy and reversal of resistance to such treatments, and regulation of the tumor survival environment. It has been confirmed that curcumin exerts its antitumor effects on GIC through these mechanisms in vitro and in vivo. Moreover, treatment with curcumin is safe and tolerable. It has been reported that curcumin promoted pyroptosis in liver cancer cells (Li W.-f. et al, 2021), induced necroptosis in prostate and lung cancer cells (Lee et al., 2021), and induced ferroptosis in breast (Li et al., 2020) and lung cancer cells (Tang et al., 2021). Curcumin has exhibited good antitumor activity and low toxicity.  Newly discovered types of regulated cell death, such as pyroptosis, necroptosis, and ferroptosis, may provide a new direction for research on the efficacy of curcumin against GIC. Curcumin is the most important component of the rhizomes of turmeric (Curcuma longa) (Waly et al., 2018). Curcumin is a hydrophobic polyphenol that has been approved by the US Food and Drug Administration based on its bio-safety (Mashayekhi-Sardoo et al., 2021). Moreover, it has demonstrated a wide range of pharmacological activities, such as antibacterial (Ibarra-Martinez et al., 2022), anti-inflammatory (Yan et al., 2021), antioxidant (Xu et al., 2021), and antitumor (Zhang et al., 2020). Curcumin has been widely reported to inhibit the proliferation of tumor cells in a concentration-and time-dependent manner in vitro (Li et al., 2017a; Fan et al., 2020; Mao et al., 2021). In numerous studies, curcumin, a plant extract with a good safety profile, has exhibited pharmacological effects on GIC both in vivo and in vitro. As demonstrated in the present review, curcumin can effectively inhibit GlC through multiple targets, mechanisms, and pathways.

Curcumin Remedies Testicular Function and Spermatogenesis in Male Mice with Low-Carbohydrate-Diet-Induced Metabolic Dysfunction
International Journal of Molecular Sciences | September 2022
Low carbohydrate diet and ketogenic diet groups had significantly lower testosterone concentrations than the normal diet group. In contrast, the diet treated with curcumin supplementation group had an increased testosterone concentration level. Curcumin increases the testosterone level through upregulating 17β-HSD expression. Curcumin, a powdered rhizome of Curcuma longa, is considered a powerful antioxidant. The antioxidant capacity of curcumin can be divided into the direct removal of reactive oxygen species (ROS) and indirect activation of antioxidant enzymes activities. These properties are related to the chemical structure of curcumin, which includes bios-α, β-unsaturated β-diketone, two methoxy groups, two phenolic hydroxy groups and two conjugated bonds, which might play important roles in anti-inflammatory and antiproliferative activities. A randomized, double-blind, placebo-controlled clinical trial showed that curcumin supplementation could increase sperm quality, including total sperm count, sperm concentration and motility, and improved the total antioxidant capacity of plasma, malondialdehyde, C-reactive protein and tumor necrosis factor (TNF). Curcumin, a phenolic compound extracted from the Curcuma longa rhizome, has antioxidant, anti-inflammatory, and anti-mutative properties. The present study shows that curcumin improved the percentage of morphologically normal sperm and testicular morphology. Alizadeh et al. showed that curcumin could improve sperm count, concentration and motility in patients with asthenoteratospermia. It is speculated that curcumin, with a conjugated structure and an enol form, could scavenge free radicals and increase the activity of antioxidant enzymes, thereby improving sperm quality. The study shows that oral curcumin (80 mg/kg) can lower lipid accumulation in liver and adipose tissue and improve the insulin sensitivity of male C57BL/6 mice with a 60% high-fat diet. Oral administration of curcumin (80 mg/kg) in Sprague Dawley rats with a 60% high-fat diet feeding showed anti-hyperglycemic, anti-lipolytic and anti-inflammatory effects by attenuating TNF-α levels. In ICR mice with spermatogenic disorders induced by scrotal heat stress, administrating curcumin (80 mg/kg) by intragastric intubation, also had antioxidative, anti-apoptotic and androgen synthesis effects.  Our results show that a low-carbohydrate diet caused a lower sperm quality and a damaged testicular histology. Administrating curcumin (80 mg/kg) could partially reverse this condition.  Mu et al. showed that curcumin reversed high-fat-diet-induced decreased expressions of Fas, Bax and cleaved caspase 3, and increased the expression of Bcl-xl. In summary, the results of our study confirmed that a low-carbohydrate diet led to a lower sperm quality and damaged testicular histology. Supplementation with curcumin may improve the impaired sperm and testis function via decreasing oxidative stress, inflammation and apoptosis.

Anti-proliferation effects of apatinib in combination with curcumin in breast cancer cells
Hormone Molecular Biology and Clinical Investigation | September 2022
The obtained results showed that all treatments of apatinib, curcumin, and apatinib-curcumin significantly decreased viability and proliferation of the breast cancer cells in a concentration‐ and time‐dependent manner. Curcumin and Apatinib-Curcumin increased apoptosis percentage in the treated cancer cells through regulation of apoptosis-related genes expression.

ERK1/2-Dependent Inhibition of Glycolysis in Curcumin-Induced Cytotoxicity of Prostate Carcinoma Cells
BioMed Research International | September 2022
Curcumin exerts chemotherapeutic effects on various types of cancers by disrupting mitochondrial homeostasis and enhancing cellular oxidative stress. Inhibition of ERK1/2 activation seems to serve as an upstream event explaining the antiglycolytic and cytotoxic roles of curcumin in prostate carcinoma cells preadapted to acidic conditions. Numerous studies have shown that the growth inhibitory effect of curcumin on various tumor cells is mediated through actions on numerous molecules in the signaling pathway, including p53, NF-κB, mitogen-activated protein kinases (MAPK), Akt/mammalian target of rapamycin (mTOR), Notch-1, nuclear factor erythroid 2-related factor 2 (Nrf2), Wnt/β-catenin, Janus kinase (JAK)/signal transducer and activator of transcription (STAT), and AMP-activated protein kinase (AMPK). Recently, curcumin has been reported to suppress the Warburg effect in various cancer cell lines by downregulating PKM2 expression through inhibition of the mTOR/HIF-1α axis. In a previous study, we reported the preferential cytotoxicity and mechanism of curcumin on PC-3AcT cells that showed high resistance to docetaxel, compared to parental PC-3 cells. Interestingly, curcumin was shown to have the activity of co-inducing apoptosis and necroptosis by increasing reactive oxygen species (ROS) production and decreasing intracellular ATP content in human prostate carcinoma cells preadapted to lactic acid-containing media. Results provide mechanistic evidence for the antiglycolytic and cytotoxic roles of curcumin through inhibition of the MEK/ERK signaling pathway in prostate carcinoma cells preadapted to acidic conditions. It is important to note that curcumin promotes both apoptosis and necroptosis for prostate cancer cells exhibiting the Warburg phenotype by acting as a dual inhibitor of glycolysis and mitochondrial function.

Piperine Enhances the Antimalarial Activity of Curcumin in Plasmodium berghei ANKA-Infected Mice: A Novel Approach for Malaria Prophylaxis
Evidence-Based Complementary and Alternative Medicine | September 2022
Curcumin has numerous pharmacological, antioxidant, anti-inflammatory, and anticarcinogenic activities. Previous studies have reported the health beneficial effects of dietary polyphenols, e.g., curcumin from turmeric for preventive or therapeutic purposes in various types of cancer. Furthermore, curcumin has well-known cytotoxic and parasiticidal effects on protozoan parasites in vitro (e.g., Leishmania, Giardia, Trypanosoma, and Plasmodium falciparum). Several studies have shown the beneficial impacts of curcumin as an antimalarial agent. For example, curcumin plays a role in disrupting Plasmodium organelles such as apicoplast, microtubules, and PfATP6 as well as affecting parasite chromatin modification through HAT inhibition. In addition, curcumin may promote the immune response against Plasmodium via increasing the reactive oxygen species. Furthermore, curcumin inhibits glycogen synthase kinase-3β (GSK3β), which affects the production of the proinflammatory cytokines by inhibiting the transcriptional activity of NF-κB. Nonetheless, the poor bioavailability of curcumin due to expansive intestinal and hepatic metabolism along with rapid elimination restricts its clinical use. However, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) of a therapeutic could be achieved by combining with bioenhancers like piperine.  The combination of piperine and curcumin can enhance the bioavailability of curcumin in human and animal models.  Recent studies reviewed that the curcumin and piperine combination possibly has prophylactic activity. The combination of curcumin and piperine provided a good antimalarial activity with a synergistic effect on Plasmodium berghei ANKA-infected mice, including inhibition of parasitemia, delayed onset of clinical signs, and prolonged survival rate. In addition, the low parasitic load in the liver, lack of elevation in ALT and AST serum, and good histopathological features of the liver suggest that piperine may serve as a potential partner that can be combined with curcumin as malaria prophylaxis.

Curcumin improves the ability of donepezil to ameliorate memory impairment in Drosophila melanogaster
Drug and Chemical Toxicology | September 2022
Curcumin and donepezil, especially at lower dose of donepezil, significantly improved the memory index and biochemical parameters compared to donepezil alone. Thus, curcumin plus donepezil offers unique therapeutic effects during memory impairment in the D. melanogaster model of neurotoxicity.

Curcumin-mediated transcriptional regulation of human N-acetylgalactosamine-α2,6-sialyltransferase which synthesizes sialyl-Tn antigen in HCT116 human colon cancer cells
Frontiers in Molecular Biosciences | September 2022
Curcumin, a natural polyphenolic compound, increases gene expressions of ganglioside-specific human sialyltransferases, hST3Gal V and hST8Sia I, in human cancer cell lines (Lee at al., 2018 a, 2018b). In this study, we investigated the effect of curcumin on hST6GalNAc I gene expression in four kinds of human cancer cell lines (colon cancer cell HCT116, lung cancer cell line A549, glioblastoma cell line U-87 MG and breast cancer cell MCF-7). As shown in Figure 1, gene expression of hST6GalNAc I assessed by RT-PCR after treatment for 24 h with different concentration of curcumin was increased remarkably in HCT116 cells, which began to increase at 30 μM curcumin and showed about 14-fold enhancement at 50 μM curcumin compared to untreated control cells.

An examination of the protective effects and molecular mechanisms of curcumin, a polyphenol curcuminoid in diabetic nephropathy
Biomedicine & Pharmacotherapy | September 2022
The anti-inflammatory, antioxidative, anti-apoptotic, and anti-fibrosis properties of curcumin, a polyphenol curcuminoid, have been demonstrated in research on diabetic nephropathy. Curcumin may have clinical protective effects on diabetic nephropathy. Curcumin played anti-inflammatory, antioxidant and anti-fibrosis effects in diabetic nephropathy. Curcumin played anti-apoptosis and promoted autophagy effects in diabetic nephropathy. Curcumin is the most active ingredient of the curcuminoids and has been shown to be safe and non-toxic in both pharmacological trials and in vivo experiments. In addition, numerous studies have demonstrated that curcumin exhibits positive biological properties such as anticancer, anti-inflammatory, hypoglycemic, antioxidant, and anti-apoptotic effects. Based on the remarkable efficacy of curcumin, researchers have begun to focus on how it can be applied to diabetes and its associated chronic complications. Curcumin has been shown to play an essential role in regulating hyperglycemia and lipid metabolism, alleviating insulin resistance], inhibiting AGEs formation and AGEs-mediated destruction, improving oxidative stress, inflammatory pathways and apoptosis. Accumulating evidence indicates that curcumin plays a vital role in the protection of multiple pathologic mechanisms in diabetes retinopathy, diabetes cardiomyopathy and diabetic neuropathy. Both clinical trials and preclinical studies have verified that curcumin is beneficial to the hypoglycemic process as well as insulin resistance improvement, and more research on diabetic nephropathy has recently emerged. A review of the underlying mechanisms of curcumin in diabetic nephropathy examined its anti-inflammation, antioxidation, anti-fibrosis, anti-apoptosis, and autophagy-promoting properties. Notable progress has been made in preclinical studies; however, clinical trials are still lacking. As a natural polyphenol curcuminoid, curcumin is safe and effective as a promising alternative therapeutic agent for the treatment of diabetic mellitus and diabetic nephropathy.

The aphrodisiac potential of β-cyclodextrin–curcumin via stimulating cAMP-PKA pathway in testicular Leydig cells
Nature | September 2022
Recent studies have confirmed the potential pharmacological actions of curcumin in inflammatory disorders, metabolic syndrome, cardiovascular disease, and neurological disorders. Beyond these beneficial properties, recent studies also revealed that curcumin potentially impacts the reproductive system. Besides, curcumin was found to have curative potential on the reproductive system function and its impairment, regulated by stress and reproductive-related hormones. Of note, researchers also demonstrated that curcumin could increase spermatozoon motility in metronidazole-treated mice.

 Combined Treatment with Curcumin and Ferulic Acid Suppressed the Aβ-Induced Neurotoxicity More than Curcumin and Ferulic Acid Alone
International Journal of Molecular Sciences | September 2022
Curcumin has been studied for its antioxidant and anti-inflammatory effects. Curcumin is a fat-soluble polyphenol abundant in turmeric, traditionally used in Indian medicine. In some in vivo and in vitro studies, curcumin has been found to have antioxidant and anti-inflammatory effects, and it is therefore attracting attention as a preventative action for Alzheimer’s disease by inhibiting Aβ aggregation including oligomerization in vitro and in vivo. Furthermore, the administration of curcumin to APPswe/PS1dE9 double transgenic mice has been found to reduce the γ-secretase component presenilin-2 and promote the degradation of aggregated Aβ.We find that combination treatment of curcumin and FA exerts a cytoprotective effect on Aβ-induced cytotoxic effects, through multiple mechanisms. These mechanisms include the suppression of Aβ aggregation and antioxidant effects, as compared to single treatment with either curcumin or FA alone. The protective effects of the combination treatment we observed were complementary and cooperative. These findings suggest that the combination of curcumin and FA may provide an effective and superior strategy for the prevention and therapeutics of Alzheimer’s disease in humans.

Specific Irreversible Cell-Cycle Arrest and Depletion of Cancer Cells Obtained by Combining Curcumin and the Flavonoids Quercetin and Fisetin
Genes | September 2022
Curcumin treatment specifically triggers senescence in cancer cells by inducing mitotic slippage and DNA damage. We show that curcumin-induced senescence is p21-dependent and characterized by heterochromatin loss. Finally, we found that flavonoids clear curcumin-induced senescent cancer cells. Our findings expand the characterization of curcumin-induced cellular senescence in cancer cells and lay the foundation for the combination of curcumin and flavonoids as a possible anti-cancer therapy.

Curcumin and capsaicin regulate apoptosis and alleviate intestinal inflammation induced by Clostridioides difficile in vitro
Annals of Clinical Microbiology and Antimicrobials | September 2022
Curcumin is found to possess a wide array of biological features including anti-oxidant, anti-tumor and also anti-inflammatory properties. Furthermore, curcumin and its derivatives, bisdemethoxycurcumin and demethoxycurcumin have been shown to exert antimicrobial activities against different bacterial species particularly multidrug resistant (MDR) strains. Curcumin has anti-inflammatory and also anti-fibrosis effects by suppressing the NF-κB and TGF-β1/SMAD-3 signaling pathways, respectively. Vasanthkumar et al. demonstrated that curcumin and CAP alone or in combination cause considerable reduction in LPS-induced overexpression of COX-2, IL-6 and TGF-β. Consistent with previous studies, findings of the present work revealed that curcumin could decrease the C. difficile-induced gene expression level

The Regenerated Capacity of Curcumin in the Migration of Epidermal Stem Cells Promotes Skin Wound Healing in a Wistar Rat
International Journal of Pharmacology | September 2022
Turmeric contains a polyphenol called curcumin, which is similar to stem cells in that it can renew identical cells and preserve proliferation and multipotency. Curcumin’s anti-inflammatory and stemness properties as well as regenerative benefits, were investigated in this study. The curcumin decreased granulation tissue intensity vs. the control group on days 7 and day 14. Curcumin significantly reduced the mean of angiogenesis vs. the negative-control group. However, curcumin significantly improves epidermal thickening vs. the negative-control group (score 1 vs. 2, p<0.05), respectively at days 21 and 28. Curcumin improves the collagen fibre, on day 21 as fascicle vs. mixed when compared to the negative-control group. While, on days 21 and 28 the mature collagen was profoundly deposited vs. moderately in the curcumin vs. control groups. Conclusion: we conclude that curcumin significantly accelerated the healing course via modulation in the amount, maturation and arrangement of collagen fibre. Curcumin had a putative regenerative property upon upregulation of CD34 as epidermal stem cell marker expression in epidermis and hair follicles.

Cocktail of isobavachalcone and curcumin enhance eradication of Staphylococcus aureus biofilm from orthopedic implants by gentamicin and alleviate inflammatory osteolysis
Microbiology | September 2022
The combination of isobavachalcone and curcumin can enhance the susceptibility of MRSA to gentamicin, thus promoting the eradication of MRSA biofilm. When administrated as cocktail in vivo, they can significantly modify local inflammation in orthopedic device-related infection and maintain trabecular bone microstructure while substantially eradication MRSA in ODRI. Although our current study did not reveal specific mechanism about the synergy of this cocktail of gentamicin, isobavachalcone and curcumin against S. aureus, their bone microarchitecture maintenance characteristic did provide us the insight and evidence for future potential topical application by incorporating the mixture of these two small molecules with conventional antibiotics, like gentamicin bone cement chain beads and antimicrobial biomaterials, etc. The combination of isobavachalcone and curcumin as adjuvants administrated together with gentamicin to significantly enhance its antimicrobial effect, which may serve as a new potential treatment strategy especially for MRSA-induced ODRI, to rationalize the use of high-level antibiotics and reduce the emergence of drug-resistant strains of bacteria.

Curcumin and Curcuma longa Extract in the Treatment of 10 Types of Autoimmune Diseases: A Systematic Review and Meta-Analysis of 31 Randomized Controlled Trials
Frontiers in Immunology | August 2022
Curcumin and Curcuma longa Extract had good clinical efficacy in the treatment of psoriasis, ulcerative colitis and rheumatoid arthritis, so Curcumin and Curcuma longa Extract could be used in the treatment of the above diseases in the future. Curcumin is the most effective ingredient extracted from the rhizomes of ginger plants such as turmeric. A number of in vitro and in vivo experiments showed that Curcumin has various pharmacological effects such as regulating immunity, anti-oxidation, inhibiting inflammation, anti-tumor, anti-angiogenesis, anti-coagulation, and scavenging free radicals. These studies suggest that Curcumin may play a regulatory role by altering the activities of enzymes, receptors, and related transcription factors. Numerous randomized controlled trials have shown that curcumin can alleviate many human diseases, including autoimmune diseases, with the main mechanisms in regulating immunity and inhibiting inflammation. Also, Curcumin is administered with few side effects, making it a potential alternative to NSAIDs and other drugs with known severe side effects. Curcumin has been shown to be a potent immunomodulator, which can modulate the activity of T cells, B cells, macrophages, neutrophils, NK cells, and dendritic cells. The diverse pharmacological activities of Curcumin stem from its ability to interact with different biological targets and signaling pathway.  Current pharmacological studies have shown that Curcumin and Curcuma longa Extract seems to reverse some clinical symptoms of many autoimmune diseases by regulating immune inflammatory biological modules, such as inflammatory factors and immune inflammatory cell activation, differentiation and immune function regulation. Curcumin and Curcuma longa Extract is an effective natural compound with a variety of therapeutic pharmacological properties and almost no side effects. Recent studies have shown that curcumin can synergistically enhance the synergistic effect of glucocorticoids and alleviate glucocorticoid-induced osteoporosis. Because of its good clinical safety, the dose of curcumin in the treatment of autoimmune diseases is mainly between 80 mg and 6000 mg. The results of Meta-analysis showed that Curcumin and Curcuma longa Extract had good clinical efficacy in the treatment of Psoriasis, UC and RA, so Curcumin and Curcuma longa Extract could be used in the treatment of the above diseases in the future.

Protective and anti-oxidative effects of curcumin and resveratrol on Aβ-oligomer-induced damage
Journal of the Neurological Sciences | August 2022
Results suggest that curcumin and resveratrol decreased ROS generation, attenuated oxidative stress, inhibited tau hyperphosphorylation, and protected SH-SY5Y cells from AβO damage. Both curcumin and resveratrol are promising supplements or medicine as therapeutic agents for the treatment of Alzheimer's disease.

Curcumin Suppresses the Progression of Colorectal Cancer by Improving Immunogenic Cell Death Caused by Irinotecan
 Chemotherapy Anticancer Section | August 2022
Curcumin, an adjuvant drug with anti-inflammatory and antitumor effects, has been studied extensively, although its synergistic antitumor effect remains unclear. Results: Irinotecan in combination with curcumin had synergistic antitumor effects in CT-26 colon carcinoma cells. Combination treatment with Irinotecan and curcumin was more effective than Irinotecan or curcumin alone. Irinotecan and curcumin combination treatment significantly upregulated ICD-related proteins including CALR and HMGB1 and had a greater antitumor effect than Irinotecan or curcumin single treatment in vivo. Curcumin may synergistically improve the antitumor effect of Irinotecan by promoting the ICD effect. Conclusion: Combination therapy with Irinotecan and curcumin may be an option for first-line chemotherapy in some patients with advanced colorectal cancer.

Effects and Mechanisms of Curcumin for the Prevention and Management of Cancers: An Updated Review
Antioxidants | August 2022
Curcumin possesses various biological activities, such as antibacterial, anti‐inflammatory, antioxidant and anticancer effects. Curcumin has shown anticancer effects on various cancers, such as breast, liver, lung, gastric and prostate cancers. For example, curcumin inhibited breast cancer cells proliferation and induced apoptosis by increasing reactive oxygen species (ROS) production. Curcumin also inhibited liver cancer. Curcumin has been selected as a third‐generation cancer chemopreventive agent by the National Cancer Institute. The anticancer effects of curcumin have been extensively studied in different cancers, such as breast, lung, colorectal, head and neck, gastric, bladder, prostate, thyroid, liver, ovarian, oral, pancreatic, cervical, tongue and brain cancers. Many studies have reported the effectiveness of curcumin in the prevention and management of various cancers, such as thyroid, breast, gastric, colorectal, liver, pancreatic, prostate and lung cancers. The potential mechanisms include inhibiting cancer cell proliferation, suppressing invasion and migration, promoting cell apoptosis, inducing autophagy, decreasing cancer stemness, increasing reactive oxygen species production, reducing inflammation, triggering ferroptosis, regulating gut microbiota, and adjuvant therapy.

Curcumin activates autophagy and attenuates high glucose‑induced apoptosis
Experimental and Therapeutic Medicine | August 2022
Curcumin is well known for its anti‑inflammatory and antioxidant effects. Accumulating evidence suggests that curcumin can act as an agent with anti‑inflammatory, antioxidant, anticarcinogenic and antilipidemic effects. Curcumin can improve gastric emptying in rats by blocking the production of oxidative stress. In addition, curcumin also induces autophagy to protect the vascular endothelial cells and reduces the cell apoptosis from the oxidative stress damage, suggesting a potential mechanism underlying the anti‑apoptosis effects of curcumin. Overall, previous studies have confirmed that curcumin has a strong antioxidant and antiapoptosis effect. Curcumin alleviated apoptosis by promoting autophagy and inhibiting the ROS/NF‑κB signaling pathway.

Identifying the Antitumor Effects of Curcumin on Lung Adenocarcinoma Using Comprehensive Bioinformatics Analysis
Drug Design, Development and Therapy | July 2022
The results of this study suggest that the therapeutic effects of curcumin on Lung Adenocarcinoma may be achieved through the intervention of INS and GCG, which may act as potential biomarkers for Lung Adenocarcinoma prevention and treatment. Curcuma longa L., also known as turmeric, has been widely used as a traditional medicine in China, India, and Southeast Asia. As the main component of turmeric, curcumin was first used to treat cholecystitis in 1937. Curcumin mediates its anticancer activity by modulating molecular targets including transcription factors, micro-RNAs, cytokines, and interfering with genes related to apoptosis and proliferation—thus inhibiting tumor cell proliferation and migration, inhibiting angiogenesis, inducing apoptosis, and increasing sensitivity to antitumor therapy. Due to its excellent pharmacological activity, curcumin is widely used in the treatment of many diseases, including gastrointestinal disease, liver cirrhosis, cardiovascular disease, diabetes, and cancer. Increasing studies suggest that curcumin inhibits the growth of lung cancer cells through multiple pathways by inducing apoptosis, inhibiting cell proliferation, and epigenetic changes. These studies have indicated that curcumin has great potential in the treatment of various diseases. We found that curcumin significantly inhibited the proliferation, migration and invasion of Lung Adenocarcinoma A549 and NCI-H1299 cells and significantly decreased the expression of INS and GCG genes.

Curcumin reduces blood-nerve barrier abnormalities and cytotoxicity to endothelial cells
Folia Morphologica | July 2022
Curcumin, a polyphenol found in the root of Curcuma longa, had favorable effects on cisplatin neuropathy in previous work. Curcumin alleviated pericyte detachment, cytotoxicity, oxidative stress, TEER reduction and tight junction protein expression. Curcumin might improve neuropathy via the restoration of BNB. Whether alterations in the BNB occur and curcumin is effective in patients with cisplatin neuropathy remain to be investigated.

The protective effect of curcumin on testicular tissue in a cryptorchid rat model
Journal of Pediatric Urology | July 2022
Curcumin administration ameliorated the histological appearance of the testis and greatly reduced the level of apoptosis in cryptorchidism rats' testicular cells. After curcumin treatment, the expression of proliferating cell nuclear antigen (PCNA) was restored in the testis tissues of cryptorchidism rats. Curcumin therapy reduced Bax expression while increasing Bcl-2 expression, according to the molecular study. Curcumin therapy also reduced malondialdehyde (MDA) levels and enhanced superoxide dismutase (SOD) levels in cryptorchidism rats' testis tissue.

Exploring the Mechanism of Curcumin on Retinoblastoma Based on Network Pharmacology and Molecular Docking
Evidence-Based Complementary and Alternative Medicine | July 2022
Curcumin shows great effects of inhibiting tumor cell proliferation, inducing apoptosis, inhibiting tumor metastasis, and inhibiting angiogenesis on a variety of tumors. Curcumin is a yellow phenolic pigment with low toxicity, wide medicinal source and low price extracted from the rhizome of Curcuma longa of the ginger family, such as turmeric, which has a wide application prospect and value in clinical treatment. We initially revealed that curcumin exerts its therapeutic effects on retinoblastoma with multitarget, multipathway, and multibiological functions, providing a theoretical basis for subsequent studies. In conclusion, this comprehensive network-based pharmacological analysis suggests a number of testable speculations on the potential molecular mechanisms of curcumin in the treatment of retinoblastoma and predicts RB1, STAT3, and CDKN2A as potential therapeutic targets.

Curcumin, thymoquinone, and 3, 3′-diindolylmethane combinations attenuate lung and liver cancers progression
Frontiers in Pharmacology Sec. Ethnopharmacology | July 2022
Results showed that triple (Curcumin  + TQ + DIM) and double (Curcumin + TQ, curcumin + DIM, and TQ + DIM) combinations of Curcumin, TQ, and DIM significantly increased apoptosis with elevation of caspase-3 protein levels. Also, these combinations exhibited significantly decreased cell proliferation, migration, colony formation activities, phosphatidylinositol 3-kinase (PI3K), and protein kinase B (AKT) protein levels with S phase reduction. Triple and double combinations of Curcumin, TQ, and DIM hindered tumor weight and angiogenesis of A549 and HepG2 implants in the chorioallantoic membrane model. Interestingly, Curcumin, TQ, and DIM combinations are considered promising for suppressing cancer progression via inhibiting tumor angiogenesis. Curcumin, the active ingredient of Curcuma longa L is the most studied compound described as a potential anticancer agent due to its multi-targeted signaling/molecular pathways (Sharma and Martins, 2020; Shah et al., 2021). Generally, Curcumin has the highest binding affinities with target proteins, followed by DIM and then TQ. Furthermore, because Curcumin, TQ, and DIM have different and common targets, we suggest treating different cancer cells. In the same context, we encourage researchers to investigate Curcumin, TQ, and DIM combination with chemotherapeutic agents investigating the effect of natural products combined with commonly used chemotherapeutics for cancer therapy.

Curcumin Alleviates D-Galactose-Induced Cardiomyocyte Senescence
Natural Products and Herbal Medicine: Safety, Efficacy, and Bioactivity | July 2022
Curcumin could be an effective anticardiac aging drug. The polyphenolic compound curcumin is derived from turmeric and possesses therapeutic and biological properties against many human health issues. Experiments in vitro and in vivo suggest that curcumin could prevent cardiovascular diseases, alleviate cardiovascular aging, and induce autophagy via various signaling pathways, including SIRT, AMPK, and mTOR. Curcumin has antioxidant, autophagy-promoting, and antiaging properties. The polyphenol compound, curcumin, extracted from turmeric, has various therapeutic uses in humans. It induces antioxidant, anti-inflammatory, anticancer, and antiaging effects. Curcumin protects against cardiovascular diseases, such as cardiac hypertrophy, heart failure, and atherosclerosis. The role of curcumin in regulating apoptosis and autophagy is well-studied, including its role in reversing the aging process and reducing oxidative stress. Curcumin ameliorates aging by promoting autophagy and reducing oxidative stress during oxidative stress-induced cardiac aging. These protective effects of curcumin in cardiac aging is consistent with the interaction between autophagy and oxidative stress. In addition, curcumin could be used as a potential pharmacological candidate for treating cardiac aging. Curcumin alleviated cardiac aging by promoting autophagy and reducing oxidative stress in vivo. The experimental results also revealed that curcumin acted as a cardioprotective agent.

The Effect of Curcumin on Lipid Profile and Glycemic Status of Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis
Evidence-Based Complementary and Alternative Medicine | July 2022
Curcumin supplementation had beneficial effects on glycemic status and some lipid parameters in patients with type 2 diabetes mellitus (T2DM).  Curcumin has a wide range of pharmacological effects, including antioxidant, anti-inflammatory, antibacterial, antiviral, antifungal, and antitumor properties. Experimental and clinical studies also have reported the beneficial effects of curcumin supplementation on lipid profile and glycemic status.  In conclusion, this meta-analysis provided evidence that curcumin has promising effects on the lipid profile and glycemic status in patients with T2DM. It indicated that curcumin might be a favorable therapeutic option for T2DM patients with mixed dyslipidemia.

Curcumin attenuates development of depressive-like behavior in male rats after spinal cord injury: involvement of NLRP3 inflammasome
Journal of Contemporary Medical Sciences | July 2022
Curcumin appears to constitute a suitable agent to reduce neuroinflammation and through it, relieve a depressive-like state.  Curcumin is a multifunctional drug and it has a lot of pharmacologic effects, like anti-inflammatory, anti-oxidant, and anti-infectious activities. Studies have reported that curcumin  improves neurological defects by inhibiting apoptosis and neuronal cell death and reducing inflammation. Considering the role of curcumin in reducing inflammation after spinal-cord injury and the role of NLRP3 inflammasome in starting of inflammation and also the role of the inflammatory process in depression after spinal-cord injury, the purpose of this study is investigating curcumin role in mood alterations in male rats after spinal-cord injury through focusing on the involvement of NLRP3 inflammasome. Our results suggested that administration of curcumin  decreased neuroinflammation. Based on the findings of the behavioral tests in the present study, because of safety and high ability to enhance the parameters related to depression, curcumin can be considered as a treatment for depression.

The Role of Curcumin in Prostate Cancer Cells and Derived Spheroids
Cancers | July 2022
Curcumin can suppress the proliferation of both androgen-dependent and androgen-independent PC cell lines. Consequently, curcumin administration seems to be useful in PC prevention, and in co-treatment with conventional therapy to halt PC progression towards mCRPC. Despite its widely reported health benefits, the use of curcumin is hampered by its poor bioavailability which limits its clinical application. In this regard, several strategies were developed to overcome these limitations, including improving the delivery system by encapsulating curcumin in the form of nanoparticles, designing novel structural analogs, and liposomal encapsulation and emulsions. Our study provides evidence that curcumin supplementation can be used as a preventative strategy and opens up new frontiers for further studies aimed at implementing the diet with nutraceuticals. In conclusion, despite different studies being carried out to identify the potential synergistic curcumin combinations with chemopreventive/therapeutic ef ficacy for inhibiting PC growth, to our knowledge, this study is the first to show the ability of curcumin used alone or in combinatorial approaches to impair the size and the viability of PC-derived spheroids.

Therapeutic Potential of Curcumin and its Derivatives on Brain Tumor Glioma Biology
Neurochemical Research | July 2022
Curcumin is a natural polyphenolic compound with several anti-tumor effects which potentially inhibit tumor growth, development, proliferation, invasion, dissemination, and angiogenesis in different human malignancies. Experimental model studies have demonstrated that curcumin attenuates glioma cell viability by G2/M cell cycle arrest, apoptosis, induction of autophagy, gene expression alteration, and disruption of multi-molecular pathways. Moreover, curcumin has been reported to re-sensitize cancer to chemotherapeutics as well as augment the effect of radiotherapy on glioma cells. In this review, we have provided an update on the in vitro and in vivo effects of curcumin-based therapy on gliomas. We have also discussed the use of curcumin in combination therapies, its effectiveness on drug-resistant cells, and new formulations of curcumin in the treatment of gliomas.

The Effect of Curcumin on Lipid Profile and Glycemic Status of Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis
Evidence-Based Complementary and Alternative Medicine | July 2002
Curcuma longa L. is a traditional medicinal plant, which is widely distributed in China and some Asian countries. Turmeric, the rhizome of Curcuma longa L, is used as a spice to improve taste and also as medicine because of its therapeutic properties. Curcuminoids, the main bioactive agents extracted from the rhizome of Curcuma longa L, is responsible for the major biological effects of turmeric. As the main present form of curcuminoids, curcumin has a wide range of pharmacological effects, including antioxidant, anti-inflammatory, antibacterial, antiviral, antifungal, and antitumor properties. Experimental and clinical studies also have reported the beneficial effects of curcumin supplementation on lipid profile and glycemic status. The results of this study showed that curcumin supplementation had beneficial effects on glycemic status and some lipid parameters in patients with Type 2 diabetes mellitus. In conclusion, this meta-analysis provided evidence that curcumin has promising effects on the lipid profile and glycemic status in patients with Type 2 diabetes mellitus. It indicated that curcumin might be a favorable therapeutic option for Type 2 diabetes mellitus patients with mixed dyslipidemia.

The Effect of Curcumin on Renal Ischemia/Reperfusion Injury in Diabetic Rats
Nutrients | July 2022
Curcumin has shown to be effective in the regulation of glycemia and lipidemia with an action mechanism similar to antidiabetic medications. In addition, recent studies have demonstrated promising effects of curcumin for the treatment of autoimmune diseases, such as type 1 diabetes. It has been also demonstrated that it could have a potential role in preventing and treating several diseases due to its antibacterial, antiviral, anti-ischemic, hepatoprotective, nephroprotective, antirheumatic and anticancer activities. his study proved the effectiveness of curcumin as a renoprotective agent in DM with I/R, becoming a promising agent for the suppression of the morbidity of DM. In addition, the study suggests that, after other preclinical studies with different formulations and administration routes designed to obtain products with higher bioavailability, with a larger sample and other methodologies for evaluating renal function and also clinical studies, curcumin can be considered a therapeutic possibility to be incorporated into the clinical treatment of diabetic patients at risk for complications of renal function. Early treatment with curcumin improved renal function in diabetic rats submitted to I/R with beneficial repercussions on renal hemodynamics and renal oxidative profile.

Curcumin as a Promising Neuroprotective Agent for the Treatment of Spinal Cord Injury: A Review of the Literature
Neurospine | July 2022
Curcumin is a promising therapeutic drug for  spinal cord injuries (SCIs)treatment because it reduces the incidence of secondary injuries.  Curcumin has antioxidant and nonsteroidal anti-inflammatory pharmacological properties. Preclinical and clinical trials have revealed its various pharmacological activities, including its anti-inflammatory, antibacterial, anticancer, and neuroprotective effects on neurodegenerative disorders. Curcumin also has hepatoprotective, nephroprotective, cardioprotective, neuroprotective, hypoglycemic, and antirheumatic activities, and its neuroprotective activity against several neurodegenerative disorders is gaining researchers’ attention. As an anti-inflammatory agent, curcumin suppresses the production of many proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1, IL-8, and monocyte chemoattractant protein 1 [8,9]. In a recent study, curcumin inhibited the hypoxia-induced upregulation of glial fibrillary acidic protein (GFAP) and neurofilament-H following hypoxia and downregulated the expression of proinflammatory cytokines, such as TNF-α and IL-1. It also suppresses glial scar formation and GFAP expression, contributing toward the development of a more favorable environment for neurological recovery. Curcumin is a neuroprotective polyphenolic compound that has benefits such as pluripotency, oral safety, long usage history, and low cost. Several animal experiments have shown that curcumin can minimize secondary injury following primary SCIs through its anti-inflammatory, antioxidant, and stem cell mobilization properties. Curcumin is an influential therapeutic agent that can potentially treat catastrophic secondary injuries in the spinal cord, including inflammation, edema, free radical injury, fibrosis, and glial scar formation. It can enhance neurological function in rats, as measured using the BBB locomotor rating scale.

Antioxidant Potential of Phytoconstituents with Special Emphasis on Curcumin
Antimicrobial and Pharmacological Aspects of Curcumin | July 2022
The medicinal properties of turmeric, the source of curcumin, have been known for thousands of years; however, the ability to determine the exact mechanism(s) of action and to determine the bioactive components have only recently been investigated. Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), also called diferuloylmethane, is the main natural polyphenol found in the rhizome of Curcuma longa (turmeric). Curcumin, a polyphenol, has been shown to target multiple signaling molecules while also demonstrating activity at the cellular level, which has helped to support its multiple health benefits such as antioxidant, anti-inflammatory, antimutagenic, antimicrobial and anticancer properties.

Curcumin improves D-galactose and normal-aging associated memory impairment in mice: In vivo and in silico-based studies
Plos One | July 2022
Curcumin, a natural flavonoid, has potent antioxidant and anti-aging properties. Curcumin significantly increased retention time (p < 0.05) and freezing response (p < 0.05) in PA and CFC, respectively. Curcumin profoundly ameliorated the levels of glutathione, superoxide dismutase, catalase, advanced oxidation protein products, nitric oxide, and lipid peroxidation in mice hippocampi. In silico studies revealed favorable binding energies of curcumin with GSTA1, GSTO1, KEAP1, BACE1, and MAOA. Curcumin improves retention and freezing memory in D-gal and nature-induced aging mice. Curcumin ameliorates the levels of oxidative stress biomarkers in mice. Anti-aging effects of curcumin could be attributed to, at least partially, the upregulation of antioxidant enzymes through binding with GSTA1, GSTO1, KEAP1, and inhibition of oxidative damage through binding with BACE1 and MAOA. We investigated the detailed effects of curcumin on oxidative stress in the D-gal and nature-induced aging mice model. Our in vivo study suggested that curcumin improves memory and rescues learning impairment by modulating oxidative stress levels. Furthermore, our in-silico study demonstrated that curcumin has good binding affinities for several molecular targets implicated in redox homeostasis. Finally, based on our in vivo and computational studies, it can be stated that curcumin improves aging-associated memory impairment by reducing oxidative overload in mice.

Effects of curcumin on low-density lipoprotein (LDL) oxidation from experimental studies to clinical practice
Excli journal | July 2022
Curcumin is a potent antioxidant and has a strong track record in the treatment of numerous diseases. Recent studies indicate that Curcumin exerts a lipid-lowering effect, and can modulate the formation of atherosclerotic plaque. Curcumin has a long history in the treatment of diseases, such as gastric and hepatic disorders, dental problems, menstrual difficulties, infectious diseases, malignancies, immune-related and metabolic disorders (Sahebkar and Henrotin, 2016; Panahi et al., 2017; Bagherniya et al., 2018; Parsamanesh et al., 2018; Gorabi et al., 2019; Mortezaee et al., 2019; Shakeri et al., 2019; Zahedipour et al., 2020; Afshari et al., 2021; Fu et al., 2021; Mohammed et al., 2021). Anti-inflammatory and antioxidant properties of Curcumin, a polyphenol, have been reported in numerous studies (Menon and Sudheer 2007; Shehzad et al., 2011; Momtazi-Borojeni et al., 2018; Farhood et al., 2019). Curcumin can improve the lipid profile of patients by reducing serum triglyceride (TG), LDL and total cholesterol levels significantly in subjects with coronary artery disease. Curcumin decreases the aortic lipid lesions and inhibits development of atherosclerotic plaques (Wongcharoen and Phrommintikul 2009). Curcumin demonstrates antioxidant activity because the benzene rings in the structure of the Curcumin molecule eliminate reactive oxygen species (ROS) (Joe and Lokesh, 1994). According to cardiac-related studies, serum levels of lipid peroxides are higher in patients with IHD; Curcumin is able to reduce lipid peroxide concentration (Stringer et al., 1989; Soni and Kuttan 1992). These actions could indicate that curcumin also inhibits ox-LDL elevation. Overall, our results suggest that curcumin could be effective in reducing LDL oxidation.

Curcumin inhibits the replication of rotavirus in vitro
Acta Virologica | July 2022
The present study aims to determine the effect of curcumin, a natural polyphenol compound, on rotavirus in a cell culture model. The anti-viral activity of curcumin was evaluated by reverse-transcriptase quantitative PCR (RT-qPCR), TCID50, and western blot techniques to assess CC50 in curcumin-treated MA104 cells as well as EC50 and SI within the infected MA104 cell line. Our findings supported that curcumin exerted an inhibitory influence against rotavirus in a dose-dependent manner and decreased the viral titer and VP6 expression by ~99% at a concentration of 30 μM.

How Curcumin Targets Inflammatory Mediators in Diabetes: Therapeutic Insights and Possible Solutions
Molecules | July 2022
Curcumin, a polyphenol derived from turmeric, is well known for its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. Curcumin’s anti-inflammatory and anti-oxidative activities against a wide range of molecular targets have been shown to have therapeutic potential for a variety of chronic inflammatory disorders, including diabetes. Curcumin’s biological examination has shown that it is a powerful anti-oxidant that stops cells from growing by releasing active free thiol groups at the target location. Curcumin is a powerful anti-inflammatory agent that targets inflammatory mediators in diabetes, and its resistant form leads to better therapeutic outcomes in diabetes complications. Moreover, Curcumin is an anti-oxidant and NF-B inhibitor that may be useful in treating diabetes. Curcumin has been shown to inhibit diabetes-related enzymes, such as a-glucosidase, aldose reductase and aldose reductase inhibitors. Through its anti-oxidant and anti-inflammatory effects, and its suppression of vascular endothelial development and nuclear transcription factors, curcumin has the ability to prevent, or reduce, the course of diabetic retinopathy. Curcumin improves insulin sensitivity by suppressing phosphorylation of ERK/JNK in HG-induced insulin-resistant cells and strengthening the PI3K-AKT-GSK3B signaling pathway. Curcumin is an anti-oxidant and NF-κB inhibitor that may be useful in preventing and treating diabetes. Curcumin has been shown to inhibit diabetes-related enzymes, such as a-glucosidase, aldose reductase, and aldose reductase inhibitors . Curcumin has been shown to have therapeutic potential in the prevention, or delaying, of diabetic retinopathy, by acting as an anti-oxidant and an anti-inflammatory, and inhibiting vascular endothelial development and nuclear transcription factors. Curcumin’s current applications for glycemia and diabetes-related liver illnesses, neuropathy, adipocyte dysfunction, vascular diseases, nephropathy, and pancreatic disorders were described in. Curcumin has shown efficient anti-inflammatory, anti-apoptotic and anti-oxidant potential. In patients with metabolic syndrome, short-term treatment with a curcuminoid-piperine combination reduced inflammatory status dramatically. Curcuminoids are effective, safe and natural CRP-lowering compounds. In addition, curcumin reduces levels of inflammatory mediators and factors, such as TNF-α, INF-γ, reduces systemic inflammatory biomarkers. such as RANTES. and other cytokine levels. Curcumin also reduces the levels of inflammatory cytokines, such as IL-6 and IL-1β, and targets inflammatory mediators in insulin diabetes resistance. Curcumin restores dysfunction associated with Nrf2 that helps in diabetes resistance management. Similarly, curcumin inhibits inflammatory signaling and the expression of Kelch-like ECH-associated protein 1 (Keap1), resulting in activation of the Nrf2 system. Curcumin metabolites have shown significant results in diabetes mellitus treatment focusing on inflammatory mediators.

Curcumin Increased the Sensitivity of Non-Small-Cell Lung Cancer to Cisplatin through the Endoplasmic Reticulum Stress Pathway
Evidence-Based Complementary and Alternative Medicine | July 2022
Curcuma longa was reported to possess antitumor activity through regulating oncogene expression, cell cycle regulation, apoptosis, tumorigenesis, and metastasis. Recently, curcumin was found to promote chemotherapeutic efficiency in various cancers and diseases. For instance, Zou et al. reported that curcumin increases breast cancer cell sensitivity to cisplatin by decreasing FEN1 expression. Lu et al. found that curcumin can increase the sensitivity of paclitaxel-resistant non-small-cell lung cancer cells to paclitaxel through microRNA-30c-mediated MTA1 reduction. Recently, curcumin was found to increase effects of irinotecan through mediating the ER stress pathway in colorectal cancer cells. Misra et al. found that curcumin regulates ER stress through cAMP responsive element-binding protein H.  Curcumin can enhance the chemosensitizing effect of non-small-cell lung cancer cells by targeting the ER stress pathway. Taken together, this study demonstrated curcumin can increase DDP sensitivity of non-small-cell lung cancer cells through mediating the ER stress pathway. The results of this study proposed a possible mechanism of curcumin improving DDP sensitivity in non-small-cell lung cancer cells and may shed a little light on developing the molecular targets in the ER stress pathway to overcome the DDP resistance in non-small-cell lung cancer.

Curcumin and metformin synergistically modulate peripheral and central immune mechanisms of pain
Scientific Reports | June 2022
Curcumin is a natural polyphenol and has beneficial therapeutic effects on pain. Curcumin has been used as an analgesic adjuvant with several analgesic drugs, allowing synergistic antinociceptive effects. Coadministration of curcumin and metformin at a 1:1 fixed ratio of their ED50 doses significantly reduced the dose required to produce a 50% effect compared to the theoretically required dose in phase II of the formalin test with a combination index value of 0.24. Our findings suggest that curcumin exerts synergistic anti-inflammation with metformin with no potential CNS adverse effects. Curcumin has been used as a traditional herbal remedy for centuries throughout Asia due to its pleiotropic activities, including anti-inflammatory, antioxidant, and anticancer. It is a well‐tolerated natural product causing no or minimal toxicity in short- and long-term use. Consequently, it was declared “generally recognized as safe” by the US Food and Drug Administration (FDA)21. Moreover, the therapeutic effectiveness of curcumin in nociceptive, inflammatory, and neuropathic pain has been reported in numerous animal models and humans. Dual treatment with curcumin and metformin has been reported in diabetic mellitus, diabetes-induced comorbidities, nephrotoxicity, hepatocellular carcinoma, pancreatic cancer cells, and breast cancer, with the results suggesting synergistic effects. Moreover, metformin and curcumin have different mechanisms of action in pain modulation, which indicates the potential for exerting greater analgesia when administered together.  In summary, this study suggests for the first time that curcumin combined with metformin exerts synergistic anti-inflammatory effects in both in vitro and in vivo conditions. Curcumin synergistically augmented the inhibition of nitric oxide and proinflammatory cytokines by metformin both in RAW 264.7 macrophage and BV-2 microglial cells.  Moreover, the combined therapy using curcumin and metformin showed no considerable CNS adverse effects in naïve mice. Hence, this study supports the possibility of combined use of curcumin and metformin in the treatment of pain with the least amount of medication while taking the easiness of administration, cost of the therapy, and side effect profile of medicines into the account.

 Combined Curcumin and Luteolin Synergistically Inhibit Colon Cancer Associated with Notch1 and TGF-β Signaling Pathways in Cultured Cells and Xenograft Mice
Cancers | June 2022
A combination of luteolin (30 µM) and curcumin (15 µM) was selected as the optimum combination for the study due to a low combination index of 0.25 and its highest synergistic inhibitory effect on the growth of two human colon cancer cell lines CL-188 and DLD-1. Consistent with in vitro results, intraperitoneal injection of luteolin at 10 mg/kg body weight and curcumin at 20 mg/kg body weight in BALB/C Foxn nude mice for a 2-week period synergistically inhibited CL-188 cell-derived tumor growth. Further analysis showed that the synergistic anti-colon cancer effect exhibited by curcumin and luteolin was mediated through the downregulation of the effector protein Notch1, to induce growth cycle arrest, promote apoptosis, and TGF-β signaling inhibits angiogenesis and invasion in vitro and in vivo. These data demonstrate that a combination of curcumin and luteolin exerts an anti-colon cancer effect through the modulation of Notch1 and TGF-β signaling pathways, well-known in cancer growth, invasion, and metastasis.

Antioxidant Potential of Phytoconstituents with Special Emphasis on Curcumin
Antimicrobial and Pharmacological Aspects of Curcumin | June 2022
Curcumin, a polyphenol, has been shown to target multiple signaling molecules while also demonstrating activity at the cellular level, which has helped to support its multiple health benefits such as antioxidant, anti-inflammatory, antimutagenic, antimicrobial and anticancer properties. Curcumin has received worldwide attention for its multiple health benefits, which appear to act primarily through its anti-oxidant and anti-inflammatory mechanisms. Many major diseases such as liver problem, myocardial infarction, diabetes, cancer are believed to be associated with lipid peroxidation and thus causing major cell damage. Curcuminoids and other polyphenols in turmeric can ameliorate and prevent lipid peroxidation, can stabilize the cell membrane, hence proving its significant role in prevention of atherosclerosis. Inhibitory action of   curcumin  on lipid accumulation, oxidation, nitric oxide as well as the formation of inflammatory molecules, nuclear factor-kappa B- (NF-kB-) dependent gene expression, and its activation can thus influence therapeutic potential of turmeric in the treatment of pancreatic, hepatic, cancer and intestinal diseases. Curcumin can produce promisable symptomatic relief on external cancerous lesions in human. Along with this, curcumin has resulted to be effective in preventing and treatment of many of the neurodegenerative disorders as a free radical scavenger including Alzheimer’s disease. Also after giving short-term supplementation it has proved to reduce hematuria, proteinuria, including systolic blood pressure in patients with relapsed or refractory lupus nephritis. By referring all the literature, Curcumin can be considered as a safe adjuvant therapy. The previous studies had indicated that the high antioxidant properties of turmeric was found to inhibit cellular lipid peroxidation and can also ameliorate other oxidative damage caused by free radicals. Thus Turmeric is proven to be an important source of high contents of flavonoids, polyphenols, tannins and ascorbic acid. Curcumin as important phytoconstituent of turmeric varieties is and effective and important antioxidant compound and which can be effective in management of various diseased conditions.

Efficacy of Curcumin on Treating Cancer Anorexia-Cachexia Syndrome in Locally or Advanced Head and Neck Cancer: A Double-Blind, Placebo-Controlled Randomised Phase IIa Trial
Journal of Nutrition and Metabolism | June 2022
Curcuminoids are the extracts from curcumin, which both in vitro and in vivo studies have shown the inhibitory effect of NF-kB through intracellular phosphorylation. Siddiqui et al. demonstrated that 100 mg/kg of curcumin prevented weight loss in MAC16 colon tumour mice. Moreover, the increasing dose of curcuminoid (up to 250 mg/kg) showed a 25% increase in body weight in mice. Additionally, Gil da Costa et al. discovered preventing myolysis in HPV-16-infected mice from curcuminoids by the mechanism of downregulation of NF-kB synthesis resulted in increased muscle mass or delayed muscle wasting compared with controlled mice. For curcumin in clinical studies, Gupta et al. showed that patients with solid cancer receiving chemotherapy and curcumin for eight weeks showed a significant improvement in their quality of life and a declined NF-kB level compared with the controlled arm. Recently, our previous study showed that 800 mg/day of curcumin delayed the progression of handgrip muscle strength loss and basal metabolic rate significantly among patients with solid cancer, as well as there were no serious adverse events. Our study results showed significantly improved skeletal muscle mass with the use of curcumin compared with matching placebo, in which the difference in the percent change in muscle mass between the groups was significant. Moreover, body fat mass among patients treated with curcumin showed a slower decline than patients treated with matching placebo, even though no statistically significant difference was noted between the two groups, but the trend seems to favour curcumin. Our study showed that patients treated with curcumin improved handgrip strength at week 8, but loss of handgrip strength was observed in the matching placebo group. Furthermore, in vivo studies demonstrated curcumin's crucial significant immunomodulatory effect by stimulating PBMC proliferation and cytokine production. Our study results supported the related in vivo study that curcumin administration for eight weeks resulted in less lymphocyte suppression compared with the matching placebo group. The potential role of curcumin regarding the immunomodulatory effect should be further investigated among patients with cancer during treatment with chemotherapy or immunosuppressive agents. For safety endpoint, phase I studies suggested that curcumin at a dose up to 8,000 mg once daily orally can be safely administered without dose-limiting toxicity. Our study results demonstrated that curcumin was well tolerated at a dose of 4,000 mg/day and showed only mild grade of adverse events. No serious adverse events were reported.

Review of the Effects and Mechanism of Curcumin in the Treatment of Inflammatory Bowel Disease
Frontiers in Pharmacology | June 2022
Curcumin has been used as a traditional herbal medicine in India and Southeast Asia for thousands of years. It is often used to treat biliary tract diseases, anorexia, rhinitis, cough, rheumatism, and various chronic inflammatory diseases. Due to its extensive biological activities, it has received widespread attention from researchers in recent years. Current researching indicates that curcumin has high medical value, including anti-inflammatory, antioxidant, anti-tumor, anti-apoptotic, anti-fibrosis, immune regulation and other effects, and can be used to treat a variety of diseases (Salehi et al., 2019). It is involved in many significant genetic and biochemical pathways (Karthikeyan et al., 2020; Moniruzzaman and Min, 2020; Beyene et al., 2021). Curcumin is associated with many cellular targets (i.e., NF-κB, JAKs/STATs, MAPKs, TNF-γ, IL-6, PPARγ, and TRPV1) that effectively reduce the progression of IBD. The research of curcumin and related formulations for IBD treatment has surged over the decade (Kahkhaie et al., 2019; Sharma et al., 2019; Patel et al., 2020). So far, a large number of basic and clinical studies have shown that curcumin has the effect of treating IBD and also can maintain the remission of IBD (Yang H. et al., 2017). In this review, the researches of IBD genetics and pathogenesis and curcumin molecular targets in IBD in recent years are summarized in order to provide reference for further research and application of curcumin. Current researching indicates that curcumin has high medical value, including anti-inflammatory, antioxidant, anti-tumor, anti-apoptotic, anti-fibrosis, immune regulation and other effects, and can be used to treat a variety of diseases. A large number of basic and clinical studies have shown that curcumin has the effect of treating IBD and also can maintain the remission of IBD. In this review, the research of curcumin on IBD in recent years is summarized in order to provide reference for further research and application of curcumin. At present, many researches have proved that curcumin is safe and effective through DBPC test (Heger, 2017). Curcumin may not fit medical chemists’ definition of the perfect drug, but many in vitro, in vivo and clinical trials have irrefutably confirmed its medicinal potential (Li et al., 2015; Beloqui et al., 2016; Yang et al., 2018; Yue et al., 2019; Wei et al., 2021). We searched ClinicalTrials.gov to identify current clinical trials evaluating curcumin treatment for IBD. A total of 10 trials were included. Three of them have been completed and five are in phase 3. Curcumin has less adverse reactions and high safety during use. As a potential chemotherapeutic drug, it shows a good application prospect in both basic experimental researches and clinical trials of IBD over the decades (Shapira et al., 2018; Sadeghi et al., 2020; Sugimoto et al., 2020; Banerjee et al., 2021).

A study on the effects of inhibition mechanism of curcumin, quercetin, and resveratrol
Journal of Biomolecular Structure and Dynamics | June 2022
Curcumin is the much better inhibitor than quercetin and resveratrol for hGR according to both in vitro and in silico studies. Curcumin, a potential inhibitor of hGR, can be used in drug design to target the glutathione system in cellular injury.

Curcumin as adjuvant treatment in patients with non-alcoholic fatty liver (NAFLD) disease: A systematic review and meta-analysis
Complementary Therapies in Medicine | June 2022
Turmeric (Curcuma longa) has active constituents in its rhizome called curcuminoids, with the most prominent curcuminoid called curcumin. Curcumin is acknowledged as a powerful antioxidant and anti-inflammatory agent. Curcumin is given through an oral capsule and taken daily.  Two trials’ participants received 500 mg curcumin and 5 mg piperine/day as intervention. A review reported that the consumption of curcumin significantly reduced liver enzymes, decreased low-density lipoprotein and total cholesterol among non-alcoholic fatty liver disease (NAFLD) patients. Another review found curcumin showed significant effects on fasting blood sugar, insulin level, and homeostasis model of assessment insulin resistance8 among women with polycystic ovary syndrome. Curcumin is anticipated to function as antiviral drugs to treat the current COVID-19 virus based on in vitro and in vivo studies as it showed high inhibitory activity towards the virus. Computer simulation and molecular docking showed the good ability of this monomer to bind to the COVID virus and host target so that they could block the virus-host binding sites. Curcumin has been shown to improve non-alcoholic fatty liver disease (NAFLD) severity and increase liver steatosis resolution compared to the placebo groups. Besides improving the liver ultrasonographic findings, curcumin also reduced serum liver enzymes, total cholesterol, and BMI. There is no major side effect, and our findings showed no difference in the adverse effect between the two groups. Curcumin was also found to reduce triglycerides if taken more than eight weeks’ duration.  Our meta-analysis shows that curcumin has favorable effect on liver ultrasonographic findings, reduced serum liver enzymes, total cholesterol, and BMI in participants with non-alcoholic fatty liver disease (NAFLD). Therefore, promoting curcumin as an adjuvant treatment on non-alcoholic fatty liver disease (NAFLD) patients might be justified.

Profiling of curcumin-treated T47D human breast cancer cells by a system-based approach
Gene Reports | June 2022
This study investigated the regulatory mechanism of curcumin in breast cancer cells. Curcumin triggers cell death-related pathways and regulates the metabolism of lipids and apoptotic processes in T47D cells. Curcumin signature had significant prognostic power. Regulatory network analyses found specific proteins, microRNAs and transcription factors as the hub nodes, which corresponded to the effects of curcumin treatment. This work provides a picture of the cytotoxicity mechanism of curcumin and potential therapeutic targets for treatment optimization of breast cancer.

The efficacy of curcumin-piperine co-supplementation on clinical symptoms, duration, severity, and inflammatory factors in COVID-19 outpatients: a randomized double-blind, placebo-controlled trial
Trials | June 2022
Curcumin as an anti-inflammatory agent can have a positive effect on the control of COVID-19 complications. This study aimed to assess the efficacy of curcumin-piperine supplementation on clinical symptoms, duration, severity, and inflammatory factors in patients with COVID-19. Forty-six outpatients with COVID-19 disease were randomly allocated to receive two capsules of curcumin-piperine; each capsule contained 500 mg curcumin plus 5 mg piperine or placebo for 14 days. The present study results showed that curcumin-piperine co-supplementation in outpatients with COVID-19 could significantly reduce weakness.

Curcumin attenuates vascular calcification via the exosomal miR-92b-3p/KLF4 axis
Experimental Biology and Medicine | June 2022
Curcumin is a natural polyphenolic compound that has hypolipidemic, anti-inflammatory, and antioxidant effects on the cardiovascular system. Exosomes are known to have extensive miRNAs for intercellular regulation. Our study suggests that curcumin  attenuates vascular calcification.

Role of Curcumin in the Management of Schizophrenia: A Narrative Review
Indian Journal of Psychological Medicine | June 2022
Curcumin is a polyphenolic molecule derived from Curcuma longa. In traditional medicine, turmeric is commonly used as an anti-inflammatory and antiseptic agent. Its antioxidant property and low toxicity potential are utilized in physical disorders like rheumatioid arthritis, cardiovascular disorders, asthma, and neuropsychiatric disorders like Alzheimer’s dementia and Parkinsonism. There are no available reports of toxicity in humans following long-standing use of curcumin. An exploratory proof-of-concept study examined the effects of curcumin combined with piperine (from black pepper extract–used to improve the bioavailability of curcumin) as an add-on to the ongoing antipsychotic treatment. Fifteen chronic schizophrenia patients were randomized to receive 1 g vs 4 g of add-on curcumin and piperine compounds. At the end of 16 weeks, both groups showed significant improvements in total scores and general psychopathology subscale of the Positive and Negative Syndrome Scale (PANSS). Both the doses were tolerated well without much adverse effects. The role of curcumin in the management of depression and bipolar disorder has been proposed recently. Curcumin as an add-on to antidepressant drugs has been convincingly shown to reduce depressive symptoms, compared to placebo add-on. A recent meta-analysis supported the utility of adjunctive curcumin in the management of depression and anxiety disorders. Notably, curcumin was tolerable and safe in all those randomized human clinical trials.  Preclinical studies support curcumin’s role in ameliorating the metabolic side effects of antipsychotics such as olanzapine 28 and clozapine. Also, pretreatment with curcumin prevented the development of tardive extrapyramidal syndromes. In both haloperidol and clozapine exposed rats, pretreatment with curcumin successfully prevented the development to tardive orofacial movements. Curcumin’s antioxidant, free radical scavenging, and antiapoptotic properties are postulated to underlie this preventive mechanism. Preclinical studies also reported curcumin’s beneficial effects in preventing and reducing extrapyramidal and metabolic side effects. Preclinical and clinical trials reported curcumin’s potential role in the management of schizophrenia.

Comparative Study of the Anticoagulant Activity of Zingiber Officinale and Curcuma longa Rhizomes Extracts in Blood Samples of Normal Individuals
Pakistan Journal of Medical & Health Sciences | June 2022
The in vitro anticoagulant effect demonstrated that ginger and curcumin extracts had equal anticoagulant activity, but curcumin has a higher anticoagulant impact with considerable PT prolongation.

Curcumin and Related Compounds in Cancer Cells: New Avenues for Old Molecules
Frontiers in Pharmacology | June 2022
Curcumin and related compounds are bioactive compounds mainly derived from natural sources and known for years for their pleiotropic effects. These compounds show anti-viral, anti-fungal, anti-microbial and anti-tumor effects (Chiao et al., 1995; Beauregard et al., 2015; Balaha et al., 2021), mainly ascribable to anti-inflammatory and antioxidant activities. Curcumin and derivatives have been proposed as potential therapeutic agents in selected cancer types such as prostate, colon, breast and thyroid cancer (Schwertheim et al., 2017; Mbese et al., 2019) and their anticancer effects have been tested in vitro and in vivo in combination with chemotherapeutic agents and radiotherapy (Yu et al., 2021). Curcumin has shown to amplify the anticancer effects of drugs (e.g., doxorubicin, cisplatin, gefitinib) and radiotherapy (Tan and Norhaizan, 2019; Ashrafizadeh et al., 2020). For instance, curcumin displays a synergistic effect with some chemotherapeutic agents such as 5-fluorouracil and oxaliplatin (Farhood et al., 2019) while protecting normal tissues from cell death, and therefore without side effects.

Effect of Interval Training and Curcumin on BAX, Bcl-2, and Caspase-3 Enzyme Activity in Rats
Gene, Cell and Tissue | June 2022
Curcumin is a polyphenol used as a painkiller, anti-inflammatory agent, and a source of powerful antioxidants. Numerous studies have confirmed the biological effects of curcumin and introduced it into various pathological conditions. It contains many anti-diabetic, anti-tumor, anti-inflammatory, and antioxidant agents. Curcumin activates the caspase-3 enzyme and releases cytochrome c from the mitochondria to the cytosol. Also, curcumin can improve athletic performance and delay exercise fatigue. Studies have shown that curcumin synergizes with 5-fluorouracil and enhances apoptosis in cancer cells in xenograft mice. If curcumin enters cancer cells, it activates programmed cell death pathways.  High-intensity interval training did not reduce BAX protein, but the training and curcumin supplementation increased Bcl-2 protein expression and neutralized the BAX effect. Curcumin supplementation combined with intense interval training resulted in synergy and reduced cell programming mortality. Therefore, curcumin supplementation and intermittent exercise can reduce cell apoptosis and programmed cell death.

Curcumin Blocks High Glucose-Induced Podocyte Injury via RIPK3-Dependent Pathway
Frontiers in Cell and Developmental Biology | June 2022
Curcumin, a natural hydrophobic polyphenol compound responsible for the yellow color in Curcuma longa, has gathered attention from various research fields due to its natural antioxidant, anticancer, anti-inflammatory, antiangiogenic, and antiapoptotic effects (Gururaj et al., 2002; Majithiya and Balaraman, 2005; Koeberle et al., 2009; Perrone et al., 2015; Zhang et al., 2020). The effect of curcumin on high glucose-induced podocyte injury has been discussed in few studies, mainly focusing on curcumin’s antioxidant and anti-inflammatory properties (Kanitkar et al., 2008; Meng et al., 2013; Den Hartogh et al., 2019). Curcumin has recently been reported to have a protective effect on hepatocyte or neuronal cells prone to necroptosis (Dai et al., 2013; Lu et al., 2016). Our study showed that curcumin had protective effects against oxidative stress, inflammatory response, and fibrosis in high glucose-induced podocyte injury, eventually improving podocyte function. These renoprotective effects of curcumin might be associated with its ability to inhibit high glucose-induced RIPK3 expression by inhibiting oxidative stress. Our observations suggest that curcumin might be a potential therapeutic agent to minimize the progression of podocytopathy caused by diabetes as an inhibitor of RIPK3. Results indicate that curcumin treatment can protect against high glucose-induced podocyte injuries by suppressing the abnormal expression of ROS and RIPK3. Thus, curcumin might be a potential therapeutic agent for diabetic nephropathy as an inhibitor of RIPK3.

Curcumin activates NLRC4, AIM2, and IFI16 inflammasomes and induces pyroptosis by up-regulated ISG3 transcript factor in acute myeloid leukemia cell lines
Cancer Biology & Therapy | June 2022
Curcumin, an active ingredient derived from turmeric, has been recognized for its medicinal properties, including antioxidant, anti‐inflammation, radical‐scavenging, anti-solid and -blood tumor, and so on. The anticancer effects of curcumin mainly result from multiple biochemical mechanisms that are involved in the regulation of programmed cell death, such as apoptosis, autophagy. Recent studies have found that curcumin can induce pyroptosis of solid tumor cells. Prior studies have shown that curcumin exert anti-cancer effects by induction of apoptosis and autophagy. We have discovered that curcumin can induce leukemia cell death by increasing apoptosis and pyroptosis and that activated AIM2, IFI16, and NLRC4 inflammasomes play a key role in this process. In addition, the anti-leukemia effect of curcumin is affected by the expression of GSDMD. Thus, pyroptosis may be a potential new strategy for treating leukemia, and GSDMD is a biomarker to evaluate curcumin sensitivity in the leukemia therapy.

Effect of Curcumin on Apoptosis of Acute T-Lymphoblastic Leukemia Cells
CNKI | June 2022
Curcumin can enhance the apoptosis of T-cell acute lymphoblastic leukemia (T-ALL) cells induced by Mcl-1 small molecule inhibitor UMI-77 by reducing the mitochondrial membrane potential, the mechanism may be related to the inhibition of Notch1 signaling pathway.

Curcumin inhibits the cancer‑associated fibroblast‑derived chemoresistance of gastric cancer
International Journal of Oncology | June 2022
Curcumin abrogated the CAF‑mediated activation of the JAK/STAT3 signaling pathway in GC cells. In vivo data revealed the synergistic effects of curcumin with 5‑FU treatment in xenograft GC tumors. These data strongly suggest that the suppression of the JAK/STAT3 signaling pathway counteracts the CAF‑induced chemoresistance of GC cells. It is suggested that curcumin may be a suitable natural product which may be used to overcome chemoresistance by inhibiting the CAF‑induced activation of the JAK/STAT3 signaling pathway in GC.

The effect of curcumin supplementation on delayed-onset muscle soreness, inflammation, muscle strength, and joint flexibility: A systematic review
Phytotherapy Research | May 2022
Curcumin supplementation significantly reduced serum creatine kinase activity, muscle soreness, and TNF-α concentration. Also, curcumin supplementation elicited significant improvements in maximal voluntary contraction (MVC) and range of motion (ROM). Curcumin supplementation may improve some aspects of delayed-onset muscle soreness (DOMS), including muscle damage, muscle soreness, inflammation, muscle strength, and joint flexibility.

Antiproliferative Effects of Curcumin Different Types of Breast Cancer
Journal of Cancer Prevention | May 2022
Breast cancer is one of the most frequently diagnosed malignancy among women. Turmeric is isolated from Curcuma longa. Curcumin is main curcuminoid of the turmeric which is a member of Zingiberaceae. In this current study antiproliferative effects of curcumin were investigated in luminal A breast cancer cell line MCF-7 and triple negative breast cancer cell line MDA-MB-231. Curcumin, which has antiproliferative effects on breast cancer cells, is thought to be effective in cancer treatment.

Effect of Curcumin on Hippocampal Neurons, Learning, and Spatial Memory in a Model of Global Cerebral Ischemia
Red Crescent Medical Journal | May 2022
Curcumin administration reduced spatial memory impairment in the treatment group compared to the ischemia group. These results suggest that pretreatment with curcumin can improve memory and learning disorders and hippocampal neuron damage following ischemia.

Role of curcumin in ameliorating hypertension and associated conditions: a mechanistic insight
Molecular and Cellular Biochemistry | May 2022
Since ancient times, curcumin has been in use as food spices and folk remedy to treat cough, cold, cuts and wounds, and skin diseases. Preclinical and clinical studies have indicated that curcumin acts a promising therapeutic agent in the management of a wide array of health issues, viz., hyperlipidemia, metabolic syndrome, anxiety, arthritis, cancer and inflammatory diseases. Owing to its enormous potential, recent research has been focused on the synthesis of curcumin and its analogues for the management of metabolic disorders. In the current scenario, hypertension is considered as a key risk factor due to its involvement in various pathogeneses. Mechanistically, curcumin and its analogues have been reported to elicit anti-hypertensive effect through diverse signalling pathways.

The effects of curcumin as dietary supplement for patients with COVID-19: A systematic review of randomized clinical trials.
Drug Discoveries & Therapeutics | May 2022
Accumulating evidence has been reported regarding the effect of curcumin as a dietary antiviral on patients with COVID-19. Our review revealed that curcumin might have a positive effect on relieving COVID-19 related inflammatory response due to its powerful immune-modulatory effects on cytokines production, T-cell responses, and gene expression. These findings suggest that curcumin confers clinical benefits in patients with COVID-19.

Molecular Mechanism of Curcumin and Its Analogs as Multifunctional Compounds against Pancreatic Cancer
Nutrition and Cancer | May 2022
Curcumin is a natural chemical substance obtained from plants with a wide range of pharmacological activities. Research evidence suggests that curcumin can influence PC development through multiple molecular mechanisms.  This review aims to summarize the mechanisms of action of curcumin in preclinical and clinical studies on PC and research progress in enhancing its bioavailability.

An Overview of Parkinson's Disease: Curcumin as a Possible Alternative Treatment
Cureus | May 2022
Curcumin, turmeric's active ingredient, has antioxidant, anti-apoptotic, and anti-inflammatory properties that protect tissues from the harmful effects of reactive oxygen species (ROS).  Curcumin's protective properties start with its ability to cross the blood-brain barrier due to its lipophilic nature. Curcumin has various protective properties in the brain, including protection against toxic metals and ROS. Toxic metal ions can interfere improperly with tissues in the brain, causing neurological damage. Curcumin, as a flavonoid, has antioxidant properties that are potentially stronger than typical antioxidants such as vitamins C and E. Curcumin also protects against A53T α-synuclein aggregation and monoamine oxidase B, becoming a compound of interest in treating neurodegenerative disorders such as Parkinson's disease. Curcumin has been found to protect nigrostriatal dopaminergic neurons from damage in animal models. Curcumin had protective effects on alpha7-nicotinic acetylcholine receptors after administration of 6-hydroxydopamine (6-OHDA) in rats with a curcumin dose of 200 mg/kg. Curcumin restored nigrostriatal dopamine neurons to 87.3% and 84.8%. Curcumin's ability to donate an H ion from the beta-diketone moiety is thought to be responsible for its anti-ROS properties. Curcumin protects mitochondria and neurons from the damaging effects of ROS by donating an H ion. Curcumin's powerful antioxidant capabilities, including chelation of harmful metals and lowering ROS, may help reduce inflammation and apoptosis. Because neurons are terminal tissues, reducing ROS may improve their longevity and the efficacy of pharmaceutical therapies. These findings imply that curcumin could be used in conjunction with standard Parkinson's disease medication to improve treatment and results. 

Antitumor Properties of Curcumin in Breast Cancer Based on Preclinical Studies: A Systematic Review
Cancers | May 2022
Studies have shown that curcumin administered at different concentrations inhibited proliferation, decreased viability, and induced apoptosis in human and animal breast cancer cells.  This review assesses the antitumor effects of curcumin on breast cancer reported in preclinical in vitro and in vivo animal models. We used five databases to search for preclinical studies published up to May 2021. The assessments included the effects of curcumin on the proliferation, viability, and apoptosis of breast cancer cell lineages and on tumor volume. In total, 60 articles met the inclusion criteria. Curcumin administered at different concentrations and via different routes of administration inhibited proliferation, decreased viability, and induced apoptosis in human and animal breast cancer cells.

Docking Analysis of Some Bioactive Compounds from Traditional Plants against SARS-CoV-2
Molecules | May 2022
Curcumin and its analogues are the main phytonutrients of turmeric (Curcuma longa L.) which is  widely used around the world as culinary spices, traditional medicine as well as a popular dietary supplement ingredient due to its wide range of health benefits including anti-inflammation, anti-cancer, cardiovascular regulation, respiratory, and immune system benefits. In addition, the suppression of multiple cytokines by curcumin suggested that it may be a useful approach in treating curcumin, and demothoxycurcumin exhibited high binding affinity on SARS-CoV-2 S- protein, PLpro, and RdRp. Binding of these proteins interfere with the viral entry, replication, and immune response evasion. Therefore, these compounds may have a great potential for inhibiting the virus.

Curcumin and Thymoquinone Combination Attenuates Breast Cancer Cell Lines’ Progression
Integrative Cancer Therapies | May 2022
Curcumin, the active ingredient of Curcuma longa, is the most studied compound described as a potential anticancer agent. Curcumin  targets multiple signaling/molecular pathways including, Rb, p53, mitogen-activated protein kinase, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), and nuclear factor kappa B cells (NF-κB). Previous studies have demonstrated that curcumin can inhibit cancer cell proliferation. Recently, curcumin was reported to suppress breast cancer cell proliferation and migration through autophagy-dependent AKT degradation and increased natural killer cells activity. Curcumin, TQ, and their combination induced significant apoptosis of both cells and hindered their progression. Several reports have shown the anticancer effect of either curcumin  or TQ against MCF7 and MDA-MB-231 cell lines.  One interesting finding is curcumin , TQ, and their combination had synergistic effects. Curcumin  decreased proliferation and colony formation activities in MCF7 and MDA-MB-231 cell lines. This study supports evidence from previous observations of Effenberger-Neidnicht and Schobert,31 Attoub et al,32 Masuelli et al,33 Zhou et al,34 and El-Far et al16 who reported significant increases in caspase-3 expression, protein levels, or activities in either MCF7 or MDA-MB-231 cell lines treated with curcumin. These results suggest the promising anticancer benefit of the curcumin and TQ combination against breast cancer.

Curcumin Inhibits the Growth and Metastasis of Melanoma via miR-222-3p/SOX10/Notch Axis
Disease Markers | May 2022
Due to its antiinflammatory and antioxidant properties, curcumin has been also reported to have significant health benefits, including improved brain function and anticancer/anti-therosclerotic properties. A previous study has been indicated that curcumin could inhibit breast cancer cells proliferation and invasion via repressing the NF-κB inducing genes. It has been suggested that curcumin could influence the G0/G1 phase arrest by MTA1- (metastasis-associated protein 1-) induced inactivation of Wnt/β-catenin pathway in the lung cancer cell. In gastric cancer, curcumin could induce MMP proteins dissipation and cytochrome C into the cytosol in SGC-7901 cell lines, resulting in the downregulation of migration ability and apoptosis escaping. In colon cancer HCT116 and HT29 cells, curcumin could inhibit the level and activity of hexokinase II (HKII) by a concentration-dependent manner, inducing cell apoptosis. There is also an increasing number of studies showing that curcumin can also induce apoptosis and inhibit proliferation of melanoma cancer cells. In summary, these results indicated that curcumin was a key role in impeding the proliferation, migration, and invasion ability of melanoma cells. Curcumin could inhibit the proliferation, migration, and invasion of melanoma cells. Furthermore, curcumin repress the expression of SOX10, Notch1, and HES-1, and increase the expression of miR-222-3p. In addition, inhibition of miR-222-3p expression reversed the inhibitory effect of curcumin the growth of melanoma cells. Curcumin enhances the miR-222-3p level to reduce SOX10 expression, and ultimately inactivates the Notch pathway in repressing melanoma proliferation, migration, and invasion. According to the above, curcumin represents a potential therapeutic agent for the treatment of melanoma.

Curcumin inhibits spike protein of new SARS-CoV-2 variant of concern (VOC) Omicron
Computers in Biology and Medicine | May 2022
Curcumin, among seven phytochemicals, was found to have the most substantial inhibitory potential with Omicron S protein. Further, it was found that curcumin could disrupt the Omicron S-hACE2 complex. The molecular dynamic simulation demonstrated that Curcumin could form a stable structure with Omicron S in the physiological environment. Conclusion To conclude, Curcumin can be considered as a potential therapeutic agent against the highly infectious Omicron variant of SARS-CoV-2.

Curcumin supplementation may improve metabolic, inflammatory, and obesity markers in women with rheumatoid arthritis.
Clinical Edge Journal Scan | May 2022
Curcumin consumption for 8 weeks as a part of an integrated approach could help modulate metabolic factors, inflammation, and adiposity in women with rheumatoid arthritis. Major finding: After 8 weeks, insulin resistance, erythrocyte sedimentation rate, serum levels of high-sensitivity C-reactive protein, and triglycerides improved significantly in the curcumin supplementation vs. placebo group. Moreover, curcumin supplementation significantly decreased mean weight, body mass index, and waist circumference vs. no significant changes observed in placebo group.

Curcumin can improve Parkinson's disease via activating BDNF/PI3k/Akt signaling pathways
Food and Chemical Toxicology | May 2022
Curcumin, as one of the natural polyphenols, is significant in stimulating PI3k/Akt/glycogen synthase kinase 3 (GSK3) and BDNF/tyrosine kinase receptor B (TrkB)/PI3k/Akt signaling pathways, has great potential in neurodegenerative diseases and other different pathological settings. Curcumin can delay the progression of Parkinson's disease by protecting nerve cells.

The potential of curcumin for treating spinal cord injury: a meta-analysis study
Nutritional Neuroscience | May 2022
Curcumin had a strong significance in improving functional recovery after spinal cord injury. When curcumin was administered daily, it had a stronger effect than single-dose treatment or weekly administration. Curcumin also significantly reduced the expression of GFAP (Glial fibrillary acidic protein) marker compared to untreated groups.  These findings suggest that daily administration of curcumin can be an effective approach to improving functional recovery after spinal cord injury.

Therapeutic role of curcumin in adult neurogenesis for management of psychiatric and neurological disorders: a scientometric study to an in-depth review
Critical Reviews in Food Science and Nutrition | May 2022
Curcumin is a primary constituent of curcuminoid that exerts several positive pharmacological effects on aberrant neurogenesis. We explore the mechanisms by which curcumin regulates adult neurogenesis and in turn affects psychiatric diseases, i.e., depression and neurological disorders among them traumatic brain injury (TBI), stroke, Alzheimer’s disease (AD), Gulf War Illness (GWI) and Fragile X syndrome (FXS). This review aims to elucidate the therapeutic effects and mechanisms of curcumin on adult neurogenesis in various psychiatric and neurological disorders. Specifically, we discuss the regulatory role of curcumin in different activities of neural stem cells (NSCs), including proliferation, differentiation, and migration of NSCs. This is geared toward providing novel application prospects of curcumin in treating psychiatric and neurological disorders by regulating adult neurogenesis.

The Impact of Curcumin on the Inflammatory Profile of SW982 Cells in a Rheumatoid Arthritis Model
Journal of Immunology Research | May 2022
Curcumin, a natural polyphenol extracted from Curcuma longa, possesses plenty of proven properties, beneficial in ameliorating autoimmunological diseases, such as rheumatoid arthritis. Due to its structure, curcumin is a free radical scavenger, reducing redox-related inflammatory signaling. Profitable attributes of curcumin have been shown to lay a heavy impact on the functionality of rheumatoid arthritis by reducing their survivability and hence the number of overproliferating cells, decreasing expression of IL-1β, TNF-α, and COX-2 proteins and diminishing production of tissue destroying metalloproteinases. Presented anti-inflammatory properties, safety, and low cost of usage make curcumin a great candidate for potential therapies, which are already tested in trials conducted on patients with Rheumatoid arthritis. Aside from proving the overall anti-inflammatory properties of curcumin, results of conducted experiments showed some of the molecular basics of its action. Conducted investigations indicate the promising role of curcumin in decreasing the inflammation, enhancing its position as the potential compound in potential rreumatoid arthritis therapies.

Therapeutic Effects of Curcumin on Osteoarthritis and Its Protection of Chondrocytes
Alternative Therapies in Health and Medicine | May 2022
The curcumin  group show higher improvements in safety, joint mobility, and inhibition of inflammation. In-vitro experiments showed that curcumin  inhibited the apoptosis rate of chondrocytes and the levels of inflammatory factors, while the Wnt/β-catenin inhibitor did the opposite. Curcumin can effectively decrease the pathological results of OA, with a remarkable safety profile; its mechanism may be the activation of the Wnt/β-catenin signaling pathway to inhibit the inflammatory reaction and apoptosis in chondrocytes.

Curcumin treats endometriosis in mice by the HIF signaling pathway
American Journal of Translational Research | May 2022
Curcumin has become a hot topic in medical research because of its various pharmacological activities, such as anti-inflammatory and antioxidant. Curcumin has therapeutic effects on a variety of human diseases, including cancer, cardiovascular disease, diabetes, arthritis, neurologic disorders, Crohn’s disease, and cardiovascular disease. The modulation of curcumin for tumors has received the most attention from researchers; approximately 37% of curcumin studies are related to tumors. Curcumin can modulate multiple cellular signaling pathways simultaneously to alleviate or prevent different types of cancer, including multiple myeloma, colorectal, pancreatic, breast, prostate, and lung cancers, because it can modulate growth factors, enzymes, transcription factors, kinases, inflammatory cytokines, and apoptotic proteins. Previous studies focused on the antioxidant stress capacity of curcumin, which reduced ROS directly by enhancing the intracellular levels of reduced glutathione and counteracted antioxidants by increasing the activity of antioxidant enzymes and activating the Nrf2-Keap1 pathway. Our study demonstrated for the first time that curcumin can treat endometriosis and improve disease hypoxia through the HIF-1α pathway. Consistent with previous studies, curcumin exhibited therapeutic effect on endometriosis by inhibiting oxidative stress, thus alleviating inflammation. The real situation may be that curcumin inhibits oxidative stress on the one hand and improves hypoxia on the other hand. The number of lesions, volume, and degree of adhesions were significantly reduced in the curcumin group compared to the negative control group and the control group. Curcumin played a role in the treatment of endometriosis by modulating the HIF signaling pathway, improving the local hypoxia of the lesion, and reducing the inflammatory state of endometriosis.

Curcumin: A therapeutic strategy for targeting the Helicobacter pylori-related diseases
Microbial Pathogenesis | May 2022
Curcumin exhibits anti-inflammatory, anti-carcinogenic, anti-oxidant properties and is widely used as a natural product-derived medicine or nutraceutical. Furthermore, curcumin has been reported to have anti-bacterial activity. Therefore, curcumin might be an effective herbal-based medicine for preventing, managing, or treating H. pylori infection. This review discusses the anti-inflammatory, anti-cancer, and anti-bacterial properties of curcumin as it pertains to gastric cancer and H. pylori-associated diseases.

Curcumin Selectively Induces Colon Cancer Cell Apoptosis and S Cell Cycle Arrest by Regulates Rb/E2F/p53 Pathway
Journal of Molecular Structure | May 2022
Curcumin has anti-inflammatory and anti-tumor activity.  Curcumin induces cells apoptosis through p53-mediated mechanism. Curcumin destabilizes cell cycle distributions by Rb/CDK/E2F signaling pathway. Curcumin inhibits tumor growth in vivo. Our data showed that curcumin preferentially and, in a dose, dependent way inhibited colon cancer cells proliferation, but was not toxic to normal colon mucosa epithelial cells. Curcumin induced apoptosis through a p53-mediated mechanism. Curcumin may be a potential strategy for the treatment of colon cancer.

The effect of curcumin on the risk of mortality in patients with COVID-19: A systematic review and meta-analysis of randomized trials
Phytotherapy Research | April 2022
Curcumin is a natural polyphenolic compound with multiple benefits, including antiviral, anti-inflammatory, anticoagulant, antiplatelet, and cytoprotective, which have been demonstrated to be advantageous in reducing the progression of several inflammatory illnesses (Rattis, Ramos, & Celes, 2021). The aforementioned effects have made curcumin one of the potential treatment options for patients with COVID-19. Since the pathophysiology of COVID-19 is known to involve life-threatening inflammatory reactions, cytokine storms, and coagulopathy, curcumin can be advantageous due to its anti-inflammatory effects via the inhibition of inflammasome formation (Yin et al., 2018). In addition, curcumin also demonstrates antiviral effects via its ability to bind to the viral primary protease (Mpro) enzyme of SARS-CoV-2, which is required for viral replication. Curcumin also prevents viral attachment and passage into the host cell with great potency (Dourado et al., 2021). The ability of curcumin in inhibiting the virus-receptor interaction is in two ways, according to modeling studies: it inhibits both the spike protein and the ACE2 receptor (Manoharan et al., 2020). Previously in this journal, the findings of the randomized trial reported by Hassaniazad et al. (2021) suggest that curcumin can accelerate the recovery of acute inflammatory phase in patients with COVID-19 by modulating inflammatory immune responses.

Curcumin as a Potential Therapeutic Agent in Certain Cancer Types
Cureus | April 2022
Curcumin has no noticeable toxicity and, in combination with existing chemotherapeutic agents, is a superior treatment option for certain cancer types. The potential applications of curcumin include the prevention and treatment of cancer, anti-inflammatory/antioxidant, and antiangiogenic activities. These beneficial effects of curcumin are exerted by modulating signaling molecules, including cytokines, chemokines, transcription factors, adhesion molecules, microRNAs, tumor suppressor genes, etc.. Several studies have shown the antitumor activity of curcumin on breast cancer, prostate cancer, brain cancer, lung cancer, and pancreatic cancer. Curcumin is a potent anti-oxidative, anti-inflammatory, and anti-tumor agent, and it is extracted from rhizomes of Curcuma species. Curcumin, as a cancer treatment agent, is recognized to affect multiple targets in different stages of cancer, including angiogenesis, proliferation, metastasis, and apoptosis. The molecular mechanism of action of curcumin has been studied comprehensively. It exerts this effect by interfering with several cell-signaling pathways as well as inducing and inhibiting the production of various growth factors, enzymes, or cytokines. Its therapeutic effects for the breast, lung, prostate, intestinal, liver, and hematological malignancies have been proven in the pre-clinical as well as in vivo studies.

Effects of Curcumin on Inflammatory Response During Exercise-Induced Muscle Damage
Biointerface Research in Applied Chemistry | April 2022
The results of this study explain that curcumin was able to provide anti- inflammatory effects by reducing pro-inflammatory cytokines such as IL-6, IL-8, TNF-α. Curcumin can also reduce muscle pain intensity, decrease CK activity, and increase ROM. The curcumin dose showed to reduce various inflammatory responses due to EIMD. Therefore, it is recommended that curcumin be used in individuals who carry out physical activities, leading to muscle damage and inflammation. Curcumin's anti-inflammatory benefits have been well known. Curcumin works by altering COX-2 pathway signaling, resulting in decreased pro-inflammatory cytokine and prostaglandin production. Curcumin is able to provide anti-inflammatory effects by reducing pro-inflammatory cytokines such as IL-6, IL-8, TNF-a. Curcumin can also reduce muscle pain intensity, decrease CK activity, and increase ROM. We recommend that curcumin be used in individuals who engage in physical activity that results in muscle damage and inflammation.

Specific Metabolic Response of Patient-derived Organoids to Curcumin of Colorectal Cancer
Journal of Chromatography | April 2022
Curcumin has been found to be effective in suppressing various phases of colorectal cancer development. Our research provided a reference for further revealing the role of curcumin in human-derived colorectal cancer-like solid tumors.

Quality of Evidence Supporting the Role of Curcuma Longa Extract/Curcumin for the Treatment of Osteoarthritis: An Overview of Systematic Reviews
Evidence-Based Complementary and Alternative Medicine | April 2022
Recently, curcuma longa extract, an anti-inflammatory and antioxidant preparation) has been used in traditional Chinese medicine and Ayurveda to treat arthritis and has thus become an attractive treatment option for improving the joint condition of OA patients. Often used as an alternative medicine or dietary supplement, turmeric is typically an extract that is standardized to 80–95% curcuminoids, among which curcumin is the most active ingredient in turmeric and is “generally regarded as safe” by the US FDA. In addition, the curcumin alone has anti-inflammatory properties similar to NSAIDs. Well known for its good anti-inflammatory effect, curcuma longa extract has a potential effect on osteoarthritis, and a large number of researchers have completed several systematic reviews/meta-analyses in this research area. According to the available published evidence, curcumin may be effective and safe for the treatment of osteoarthritis.

Curcumin for attention-deficit–hyperactivity disorder (ADHD) a systematic review and preliminary behavioral investigation
Naunyn-Schmiedeberg's Archives of Pharmacology | April 2022
Curcumin has protective actions in neuropsychiatric disorders, acting as a neuroprotective agent. As a first approach, the study aimed at a systematic review of the potential effects of curcumin on cognitive performance for attention-deficit–hyperactivity disorder (ADHD). The results of the Y-Maze Test demonstrated that curcumin improved spatial memory.

Protective Effects of Curcumin-Regulated Intestinal Epithelial Autophagy on Inflammatory Bowel Disease in Mice
Gastroenterology Research and Practice | April 2022
This study was aimed at exploring the ameliorating effect of curcumin on inflammatory bowel disease (IBD) in mice induced by 3% dextran sodium sulfate (DSS) by regulating intestinal epithelial cell autophagy. Compared with that of the DSS group, the diet of mice in the curcumin group was improved, the decline of body weight was slowed down, the hair glossiness was restored, the blood in the stool gradually decreased or occulted, the DAI score was decreased, the colon tissue was significantly improved, the expressions of LC3-II/LC3-I and Beclin1 were significantly increased, and the p62 was significantly decreased. Therefore, curcumin can increase the expression level of autophagy protein in IBD mice, which may be one of the molecular mechanisms for the treatment of IBD intestinal inflammation.

Anticancer Properties of Curcumin Against Colorectal Cancer: A Review
Frontiers in Oncology | April 2022
Several studies show that curcumin belongs to a class of plant-derived chemicals that can help prevent colorectal cancer. Several possible pathways have been proven in both in vitro and in vivo animal studies. Furthermore, treatment improvements in animals with inflammatory and hereditary colorectal cancer have been discovered. The Curcuma longa roots (dried) plant are used to produce curcumin. It has been discovered to have anti-carcinogenic properties. Curcumin has the ability to target colon cancer cells specifically, while allowing normal cells to remain alone; cancerous cells die as a result of an elevation in the expression of a protein known as GADD45a (Gene activated during DNA damage). Studies in humans have shown the ability of curcumin to tilt the ratio of pathogenic microbes and beneficial microbes. Curcumin, in fact, may lower intestinal inflammation via regulating gut flora. Curcumin was showed to reduce NF-κB activation in colonic epithelial cells and increase the growth of CD4+ Foxp3+ regulatory T cells in the colonic mucosa in an experimental DSS-colitis model. Another study revealed the effect of curcumin consumed in diet could cause an increase in the species of Clostridium, Enterobacter (have the potential to enhance mucosal Treg cells by producing butyrate) and reducing the levels of Blautia and Ruminococcus species (which has been linked with individuals that has colorectal cancer) that is present in abundance

The Curcumin Supplementation with Piperine Can Influence the Acute Elevation of Exercise-Induced Cytokines: Double-Blind Crossover Study
Biology | April 2022
The most important findings of this study were the administration of curcumin associated with piperine can inhibit the elevation of plasmatic levels of some cytokines such as IL-2, TNF-α, IFN, IL-6, and IL-10. This result shows the capacity of curcumin to modulate an inflammatory response acutely induced by exercise. Supplementation with 500 mg of curcumin associated with 20 mg of piperine for seven days was able to inhibit the inflammatory response after an experimental protocol of running on a treadmill until voluntary fatigue.

The Golden Spice Curcumin in Cancer: A Perspective on Finalized Clinical Trials During the Last 10 Years
Journal of Cancer Research and Therapeutics | April 2022
Curcumin is the main curcuminoid in turmeric and has been found to possess various beneficial properties, including anti-inflammatory, antioxidant, neuroprotective,, chemopreventive, and chemotherapeutic, activities, which make this phytocompound famous. Curcumin affects multiple signaling pathways involved in cell proliferation, survival, cell death, angiogenesis, invasion, migration, and metastasis. Cancer preventive and anticancer therapeutic actions of curcumin against different types of cancers, such as breast, liver, melanoma, lung, and endometrium, are available in the literature. Based on clinical trials in cancer patients, it was concluded that even 8 g of curcumin was safe and well tolerated. As a therapeutic agent, curcumin has been subjected to clinical trials for various diseases, such as psoriasis, multiple myeloma, chronic uveitis, pancreatitis, pancreatic, colorectal, and biliary tract cancers, familial adenomatous polyposis, inflammatory bowel disorder, Alzheimer's disease, and diabetes mellitus. Various clinical trials investigated curcumin's bioavailability, its effect on various cancer types, and the efficacy of turmeric and curcumin in mitigating the side effects of cancer chemotherapy and radiotherapy. We have presented 21 clinical trials, 16 of the 21 clinical trials were associated with the effectiveness of curcumin on various types of cancer, and the other 5  clinical trials were related to the evaluation of the curcumin's efficacy in relieving the side effects of cancer chemotherapy and radiotherapy. The emerging data from clinical trials confirm that curcumin has considerable potential to treat cancer patients. It is expected that findings from ongoing and future clinical trials may help the clinical application of curcumin in managing different types of cancer.

A Comprehensive Review on the Therapeutic Potential of Curcuma longa Linn. in Relation to its Major Active Constituent Curcumin
Frontiers in Pharmacology | April 2022
Curcumin has a variety of beneficial effects on humans, according to science. Curcumin’s efficacy, safety, and pharmacokinetics have all been examined extensively in clinical studies over the last 50 years (Gupta et al., 2013; Subramani et al., 2018). Cancer, CVD, arthritis, atherosclerosis, diabetes, gastric illness, IBD, psoriasis, acquired immunodeficiency syndrome, and other inflammatory disorders are all examples of pleiotropic activities. Several studies in this review discovered the anti-inflammatory effects of curcumin, including decreased white blood cell, neutrophil, and eosinophil numbers, as well as protective effects on serum levels of inflammatory mediators like phospholipase A2 and total protein in various inflammatory disorders. Curcumin has anticancer properties by interfering with many cellular systems and inhibiting/inducing the production of multiple cytokines, enzymes, or IκKβ, TNF-α, STAT3, COX-2, PKD1, NF-κB, epidermal growth factor, and MAPK, among others. Under oxidative stress conditions,  curcumin decreased MDA and NO levels while increasing thiol, SOD, and catalase levels. Curcumin also influenced the lifespan of organisms by regulating important signaling pathways such as the mTOR, PKA, and FOXO signaling pathways. In conditions where the immune system was disturbed, treatment with C. longa and curcumin enhanced IgE, IL-4, TGF-β, IL-17, IFN-γ, and the Th1/Th2 ratio. The pharmacological effects of curcumin on respiratory, allergy, and immunologic problems suggest that curcumin may have a possible therapeutic effect on these illnesses. Curcumin delay the onset of diabetes, improve β-cell functioning, prevent β-cell death, and reduce insulin resistance in animal models.Traditional medicine has exploited dried curcumin powder to treat illnesses in history. C. longa is said to have antitoxic, anticancer, antibacterial, anti-inflammatory, and antioxidant effects (Ghotaslou et al., 2017). Rhizome powder is supposed to flavor various cuisines and treat numerous disorders, including inflammation, flatulence, jaundice, menstrual troubles, hematuria, and hemorrhage. It is also a useful ointment to treat several skin disorders. Curcumin or diferuloylmethane and numerous volatile oils. C. longa of India is particularly popular when compared with those from other countries due to its high curcumin concentration, which is the most essential and active biological ingredient responsible for its therapeutic potential (Verma et al., 2018). Curcumin shows antioxidant features close to vitamins C and E in both aqueous and fat-soluble extracts.

Effects of turmeric (Curcuma longa) and its constituent (curcumin) on the metabolic syndrome: An updated review
Journal of Integrative Medicine | April 2022
Based on studies, turmeric and its bioactive component, curcumin, due to their anti-inflammatory and antioxidant properties, have antidiabetic effects through increasing insulin release, antihyperlipidemic effects by increasing fatty acid uptake, anti-obesity effects by decreasing lipogenesis, and antihypertensive effects by increasing nitric oxide. According to several in vivo, in vitro and human studies, it can be concluded that turmeric or curcumin has important values as a complementary therapy in Metabolic syndrome. In vitro and in vivo studies have proved that curcumin has anticancer, anti-inflammatory, antioxidant and anti-fat properties. Some studies have shown that curcumin has protective effects against many chronic diseases, for example, autoimmune disorders and pulmonary diseases. It has cardioprotective effects due to its lipid-lowering properties. In the last few years, much consideration has been paid to the benefits of curcumin. It can inhibit the development of atherosclerosis and also significantly reduce the serum levels of triglyceride (TG) and low-density lipoprotein-cholesterol (LDL-C). Also, curcumin can increase insulin sensitivity through the inhibition of protein tyrosine phosphatase 1B. It has antioxidant effects in the artery and also can decrease the levels of reactive oxygen species (ROS) in the basilar artery wall. It remarkably delayed the onset of stroke. Curcumin in diabetic conditions decreased the levels of fast blood sugar, uric acid, serum urea and creatinine. Curcumin significantly alleviated the severity of liver fibrosis. Curcumin treatment lowered the increased blood pressure. It also plays a significant role in obesity and significantly decreases adiposity. One of curcumin and turmeric anti-diabetic mechanisms is decreasing the phosphorylation level of insulin and inhibiting the activation of the NF-κB. Curcumin and turmeric can treat hypertension by suppressing downregulation of eNOS.

Evaluation of the Anti-Cancer Effect of Curcumin on MCF-7 Cells in 3D Culture Conditions to Increase the Efficacy of Breast Cancer Treatment
Journal of Applied Biotechnology Reports | April 2022
Curcumin reduces the production of cellular NO and increases the production of catalase and glutathione, which confirms the results of the NO test. In addition, the release of cytochrome c from Mitochondria from cells treated with different concentrations of curcumin compared to control cells are significant. The evaluation of the toxicity effect of curcumin at concentrations of 20, 40, and 80 μM using comet assay showed that this substance induces apoptosis in MCF-7 cells in a dose-dependent manner. The findings of this study showed that the anti-cancer effect of curcumin on MCF-7 cells under 3D culture conditions could increase the effectiveness of treatment. The cancer cell survival rate actually depended on curcumin concentration.

Curcumin Alleviates DSS-Induced Anxiety-Like Behaviors via the Microbial-Brain-Gut Axis
Oxidative Medicine and Cellular Longevity | April 2022
Curcumin is a yellow polyphenol extracted from the rhizome of the ginger plant, which has been shown to have effects against both depression and anxiety. Research has indicated that curcumin affects the gut microbiome and exerts antianxiety and neuroprotective effects through the microbiota-gut-brain axis. The results suggested that curcumin can effectively relieve anxiety-like behaviors caused by DSS in mice. Further, curcumin treatment can alleviate disturbances in the gut microbiota and systemic disorders of lipid metabolism caused by DSS. Finally, through FMT, we verified that curcumin increased phosphatidylcholine in the prefrontal cortex of the mice and alleviated DSS-induced anxiety-like behaviors by modulating specific gut microbiota. We also revealed that Muribaculaceae may be a key part of the gut microbiota for curcumin to alleviate DSS-induced anxiety-like behaviors through the MGB axis. Curcumin is also believed to hold medicinal properties against many diseases, including gastrointestinal, cardiovascular, and mental diseases. High concentrations of curcumin have been detected in the gastrointestinal tract after oral administration. Supplementation of curcumin significantly enriched beneficial bacteria such as Butyricicoccus, a butyrate producing genus in the intestinal tract, and reduced Ruminococcus, and Mucispirillum, which were implicated in the development of obesity and diabetes. These findings were the basis to suggest that curcumin directly affects the gut microbiome despite its low systemic bioavailability. Curcumin can relieve inflammation and digestive tract symptoms caused by IBD.

Curcumin induces cortico-hippocampal neuronal reshaping and memory improvements in aged mice
Journal of Chemical Neuroanatomy | April 2022
Traditional medicine has long benefitted from naturally occurring molecules such as curcumin (diferuloymethane). Curcumin is extracted from the plant Curcuma longa and is known for its synaptic and antioxidant-related benefits. In this study, we tested the hypothesis that chronic curcumin treatment reduces cognitive and cellular effects of aging. Curcumin-treated mice showed improved learning and memory using the Morris Water Maze and novel object recognition task. In addition, using the Golgi-Cox stain, curcumin treatment increased spine density in all evaluated regions and increased dendritic arborization in the prefrontal cortex (PFC) layer 3 and CA3 subregion of the hippocampus. Moreover, chronic curcumin exposure increased synaptophysin and actin expression and reduced glial fibrillary acidic protein expression, a marker of astrocytes, in the hippocampus (CA1 and CA3 subregions), while simultaneously reducing the ROS-related molecule, metallothionein 3 expression in the PFC and hippocampus. Collectively, these novel findings suggest that curcumin reduces  cognitive, neuronal and astrocytic signs of aging in mice. Curcumin is the main metabolite found in Curcuma longa with potential benefits in aging. Curcumin-treated mice showed improved learning and memory in aged mice.  Curcumin treatment increased dendritic arborization in the PFC and hippocampus.  Curcumin exposure reduced astrocytic expression in the hippocampus.

Curcumin as a Potential Therapeutic Agent in Certain Cancer Types
Cureus Journal of Medical Science | March 2022
Several anticancer compounds have been extracted from plant sources such as Curcuma longa. Among these, curcumin (diferuloylmethane) has no noticeable toxicity and, in combination with existing chemotherapeutic agents, is a superior treatment option for certain cancer types. Curcumin is an important component of the curcuminoids family and is isolated from the rhizome of Curcuma longa L. (turmeric). The potential applications of curcumin include the prevention and treatment of cancer, anti-inflammatory/antioxidant, and antiangiogenic activities. These beneficial effects of curcumin are exerted by modulating signaling molecules, including cytokines, chemokines, transcription factors, adhesion molecules, microRNAs, tumor suppressor genes, etc. Several studies have shown the antitumor activity of curcumin on breast cancer, prostate cancer, brain cancer, lung cancer, and pancreatic cancer. Curcumin is a potent anti-oxidative, anti-inflammatory, and anti-tumor agent, and it is extracted from rhizomes of Curcuma species. Curcumin, as a cancer treatment agent, is recognized to affect multiple targets in different stages of cancer, including angiogenesis, proliferation, metastasis, and apoptosis. The molecular mechanism of action of curcumin has been studied comprehensively. It exerts this effect by interfering with several cell-signaling pathways as well as inducing and inhibiting the production of various growth factors, enzymes, or cytokines. Structural and chemical modifications have been tried to enhance the selectivity, bioavailability, and efficacy of curcumin for cancer. Its therapeutic effects for the breast, lung, prostate, intestinal, liver, and hematological malignancies have been proven in the pre-clinical as well as in vivo studies.

An Update on the Exploratory Use of Curcumin in Neuropsychiatric Disorders
Antioxidants | March 2022
Curcumin, the active compound of turmeric, is a polyphenol that has also been largely used as a remedy for different pathologies in Asia for several decades due to its healthy and biopharmacological properties, and its lack of adverse effects, even at high doses. Moreover, curcumin has been reported to have anti-inflammatory, antioxidant, neuroprotective, and even anti-aging and antineoplasic properties. Curcumin may exert its anti-inflammatory and antioxidant (anti-IOS) effects by influencing the synthesis of some IOS regulators, such as heme-oxygenase-1 (HO1), glutathione (GSH), catalase (CAT), and superoxide dismutase. These properties cause curcumin to have an impact on those diseases in which IOS regulation does not work correctly and are related to the disease appearance. Thus, curcumin may exert a beneficial effect on the immune system, reducing B lymphocyte proliferation by inhibiting B lymphocyte stimulator (BLYS). Curcumin can also reduce the neutrophil recruitment to areas affected by inflammation, and can also increase the phagocytic activity of macrophages. Furthermore, curcumin has proven to be an effective modulator of the endocrine system, enhancing the uptake or regulating some hormones, such as insulin. All these properties have boosted the interest of researchers in this compound in recent decades.  Recently, curcumin has also been used in different psychiatric disorders due to the likely involvement of IOS processes in their onset and evolution. In this sense, the above-described role of curcumin as an anti-IOS drug made this compound a good candidate to halt or palliate the course of these diseases. Anti-inflammatory, antioxidant, and neuroprotective properties of curcumin, along with many multi-target beneficial effects, such as the modulation of monoamine synthesis, have exponentially promoted the investigation of its properties during this last decade. Two-hundred and ninty-six articles containing research on curcumin were published in the PubMed database in 2005. In 2010, this number increased to 714 and, in 2020, to 2130. A total of 65 preclinical studies and 14 clinical trials were reported. Most of these studies were conducted on depression, approximately 88% were preclinical studies and 64% were clinical studies. In all disorders, curcumin was well tolerated, with no harmful side effects. This was not surprising, as curcumin has been used for the last centuries as an additive spice in East Asian cuisine. Moreover, curcumin was shown to be beneficial in palliating or reversing symptoms associated with psychiatry in all the studies analyzed and completed. In clinical trials, curcumin proved to be effective in alleviating both positive and negative symptoms of schizophrenia when administered together with regular antipsychotic medication. The clinical relevance of these results could be of great importance, due to the adverse events that can be caused by the extensive and chronic use of antipsychotics. In this sense, curcumin could exert its beneficial effect in schizophrenia through an inhibition of PLA2 enzyme. In depression, we found the vast majority of studies, in both preclinical and clinical domains, showed some beneficial effect of curcumin in reducing symptoms associated with depression. In addition to the recognized role of curcumin as an anti-inflammatory and antioxidant agent, positive improvement of depressive deficits could be exerted through modulation of the indolamine 2,3-dioxygenase (IDO) enzyme. Therefore, the overall effect of curcumin in this disorder seems to be mainly positive.  Overall, curcumin, due to its anti-inflammatory and antioxidant properties, has been shown to be effective in the vast majority of the studies presented.

Curcumin-Rich Curry Consumption and Neurocognitive Function from 4.5-Year Follow-Up of Community-Dwelling Older Adults
Nutrients | March 2022
Curcumin is a polyphenolic compound isolated from the roots of Curcuma longa, from which turmeric is prepared and used widely as a coloring agent, food additive and traditional Indian and Chinese medicine. For decades, curcumin and related bioactive curcuminoids (demethoxycurcumin and bisdemethoxycurcumin) have been the center of interest of scientific studies worldwide into their therapeutic potentials. Numerous laboratory studies have documented its antioxidant, anti-inflammatory, antimicrobial, antiviral, antineoplastic and antiaging activities. Curcumin is actively being investigated for its potential neuroprotective benefits. In vitro and in vivo studies show that curcumin crosses the blood–brain barrier and can bind to β amyloid (Aβ) and tau-inhibiting Aβ aggregation and modulate tau processing. Animal studies show that curcumin decreases Aβ deposition and plaque load in the brain of transgenic mouse models of AD. Experimental studies have also demonstrated that curcumin possesses beneficial antiplatelet, antidiabetic and cardioprotective activities ameliorating cardiac hypertrophy and chronic heart failure. On top of the known anti-inflammatory activities of curcumin attenuating neuroinflammation, this experimental evidence strongly suggests that curcumin has the potential to prevent accelerated cognitive decline in humans. Several animal studies have shown that curcumin improves cognitive function. Randomized controlled trials in humans are limited but suggest that curcumin could be safely and effectively used to slow cognitive decline. We found in this observational cohort study that the consumption of curcumin-rich curry in food was associated with the maintenance of higher levels of cognitive functioning over time among community-dwelling middle-aged and older Asian adults in Singapore. To our knowledge, this is the first longitudinal study demonstrating the cognitive benefits of curcumin from natural dietary food sources in humans. Curcumin exposure from dietary ingestion appears to offer neuroprotection especially through its beneficial metabolic, antiplatelet and cardioprotective properties.  There is evidence that the combination of piperine in black pepper with curcumin in turmeric increases the bioavailability of curcumin by 2000% and inhibits the intestinal and hepatic glucuronidation of curcumin. In this study, real-world observations of the potential cognitive benefits of curcumin in humans were provided in a large population-based cohort of community-dwelling older adults with follow-up over three to five years. The consumption of dietary curcumin was associated with the maintenance over time of higher functioning on attention, short-term working memory, visual spatial constructional ability, language and executive function among community-dwelling older adults. This suggests that, notwithstanding its known anti-amyloid, anti-tau, antioxidant and anti-inflammatory activities, curcumin exposure from dietary ingestion appears to offer neuroprotection especially through its beneficial metabolic, antiplatelet and cardioprotective properties. The results from the stratified analysis support this by showing that among participants with pre-existing metabolic and cardiovascular disease, curry consumption was associated with enhanced performance on attention, working memory and language executive function. In vitro and high-dose animal studies show that curcumin modulates molecular pathways that restore glucose homeostasis, lipid metabolism, endothelial function and insulin signaling and may thus offer potential cardiovascular protective effect. These observations suggest that population health in terms of healthy cognitive ageing and potential reduction of risks of dementia could be enhanced by increased consumption of curcumin in a turmeric-rich diet.  

Potential Role of Curcumin for the Treatment of Major Depressive Disorder
CNS Drugs | March 2022
Curcumin is the major biologically active polyphenolic constituent in the turmeric plant (Curcuma longa) that has been shown to have antioxidant, anti-inflammatory, neuroprotective, anticancer, antimicrobial, and cardioprotective effects. Interest in curcumin as a treatment for mental health conditions has increased and there is an expanding body of preclinical and clinical research examining its antidepressant and anxiolytic effects. Cell culture and animal studies have demonstrated that curcuminoids, and in particular curcumin, have extensive biological activity, including antioxidant, anti-inflammatory, neuroprotective, anticancer, antimicrobial, and cardioprotective effects. Turmeric has traditionally been used in Indian folk medicine to treat eye infections, skin wounds, respiratory conditions and digestive complaints, and to reduce general inflammation. More recently, interest in curcumin as a treatment for depression has increased and there is an expanding body of research confirming antidepressant and anxiolytic effects from its administration. There is an increasing body of research supporting the efficacy of curcumin as a treatment for depression.  Positive antidepressant effects were reported in six of seven trials, with the only non-significant finding identified by Bergman et al., where curcumin was used as an adjunct to pharmaceutical antidepressants and administered for the shortest treatment period of all the trials (5 weeks). Positive anxiolytic effects from curcumin administration were also identified in four trials. Interestingly, in this meta-analysis, an even larger treatment effect was identified when examining the effects of curcumin on anxiety symptoms (Hedge’s g = 2.62). In a meta-analysis conducted in 2016, it was concluded from subgroup analyses that curcumin had the highest antidepressant effects when administered to middle-aged adults, for longer treatment periods, and at higher doses.

 Investigation of the Effect of Curcumin on Protein Targets in NAFLD Using Bioinformatic Analysis
Nutrients | March 2022
Curcumin is a bioactive polyphenolic compound, isolated from Curcuma longa Linn, which is endowed with diverse pharmacological activities. Curcumin improves steatosis, inflammation, and fibrosis progression.  Curcumin may improve, or inhibit, progression of non-alcoholic fatty liver disease (NAFLD)through activation/inhibition of non-alcoholic fatty liver disease (NAFLD)-related genes. Numerous in-vitro and in-vivo investigations have indicated that curcumin exerts a positive effect at each stage of non-alcoholic fatty liver disease (NAFLD), improving both inflammation and the extent of fat deposition. Curcumin was also shown to inhibit the progression from non-alcoholic fatty liver disease (NAFLD) to fibrosis and decrease the risk of liver cancer. Emerging from these studies, therefore, are data supporting the significant clinical effect of curcumin on non-alcoholic fatty liver disease (NAFLD). Curcumin exerts its anti-diabetic, cardioprotective, hepatoprotective, neuroprotective, and antitumor effects via NFE2L2 signaling pathways. Curcumin activates NFE2L2 signaling pathways in four ways. In a high-fat and high-fructose diet (HFHFr) mouse model, NFE2L2 was downregulated, while curcumin administration could reverse the abnormal serum biochemical parameters of hepatic steatosis. Another animal study using carbon tetrachloride (CCL4) induced liver damage showed that curcumin’s protective role in reducing inflammation and oxidative stress was mediated through NFE2L2/HO-1 pathways. An in-vitro study showed that curcumin, through activation of NFE2L2, can promote lipocyte activation in stellate cells (HSCs) and repress hepatic fibrosis. In this study, we identified 14 genes in non-alcoholic fatty liver disease (NAFLD) that are likely to be the target of curcumin and observed that curcumin induces or inhibits them. According to our results, this activity of curcumin was in line with improving non-alcoholic fatty liver disease (NAFLD) based on literature. We believe that the ongoing clinical trials investigating the effect of curcumin on fatty liver could yield positive results in the future, enhancing the therapeutic status of curcumin in this metabolic disorder.

 Molecular Targets of Curcumin and Its Therapeutic Potential for Ovarian Cancer
Nutrition and Cancer | March 2022
Curcumin is a natural product found in the rhizome extract of Curcuma longa and has been extensively used over the last decades for its unique biological and medicinal properties, which include: having antioxidant, analgesic, anti-inflammation, and anti-tumor activities. Curcumin exerts its anticancer properties against ovarian cancer via multiple mechanisms: interfering with cellular interactions necessary for metastasis and recurrence of OC cells, increasing pro-apoptotic proteins as well as inducing or suppressing generation of different molecules such as cytokines, transcription factors, enzymes, protein kinases, and growth factors. Moreover, curcumin down-regulates various signaling pathways such as PI3K/Akt, Wnt/β-catenin, JAK/STAT3, and MEK/ERK1/2 axes, which at least in part have a role in inhibiting further tumor proliferation, growth, and angiogenesis. In this review, we overview the potential of incorporating curcumin into the treatment of ovarian cancer.

Curcumin in Combination with Aerobic Exercise Improves Follicular Dysfunction
Oxidative Medicine and Cellular Longevity | March 2022
Curcumin is a natural medicine containing phenol and quinone groups extracted from turmeric in the ginger family. It is well known as a safe dietary supplement worldwide. In several randomized, double-blinded, clinical trial, patients with PCOS received curcumin (in doses of 500-1500 mg 3 times daily for 1-3 months) or placebo. It is suggested that curcumin can effectively improve blood glucose, insulin resistance, and hyperandrogenemia in PCOS. Moreover, curcumin reportedly exerts numerous biological effects to manage human diseases, including cancer and neurodegenerative and metabolic disorders. Both curcumin gavage and aerobic exercise improved ovarian function.  Curcumin and aerobic exercise (irisin) can alleviate hyperandrogenism-induced ER stress and suppress the IRE1α-XBP1 pathway, which prevented ovarian GC apoptosis in PCOS-like rats, leading to the improvement in the ovarian microenvironment and promotion of follicular development.

Curcumin Suppresses Lead-Induced Inflammation and Memory Loss in Mouse Model and In Silico Molecular Docking
Foods | March 2022
Curcumin is a polyphenol primarily extracted from turmeric, and has drawn much attention in the field of natural drug discovery due to its excellent therapeutic effects, such as its antioxidant, anti-inflammation, anti-microbial, anti-arthritic, and anti-depressant activities. In addition, curcumin can modulate cognitive dysfunction and astrocyte proliferation. Research revealed that curcumin can suppress memory impairment and can attenuate cognitive deficits. In mercury chloride-treated offspring mice, curcumin treatment improved memory and learning activity, antioxidant profile, and increased AChE, serotonin, and dopamine. Curcumin also downregulated the AChE gene expressions.  Curcumin is known to have a potent antioxidant activity due to its capacity for chain-breaking, as well as the hydrogen-donating phenolic groups in its structure. Much research has also revealed the neuroprotective effects of curcumin, which operate via exerting antioxidant effects and reducing oxidative damage. Curcumin exhibits great promise as a therapeutic agent for a variety of cancers, as well as for psoriasis, and Alzheimer’s disease. It has been reported that curcumin suppresses aluminum- and Pb-induced oxidative neurotoxicity, alterations in NMDA receptors that lead to decreased antioxidant enzyme activity, and AChE dysfunctions. Thus, the present study has indicated that curcumin, a potent antioxidant compound, ameliorated lipid peroxidation and oxidative stress parameters in mice exposed to Pb, along with protecting against cholinergic dysfunction. Curcumin co-treatment effectively suppresses Pb-induced brain inflammation. Thus, Curcumin may completely bind with AchE to increase enzymatic activity, which is predicted to have dose-dependent neuroprotective effects, at least in part via exerting antioxidant and anti-inflammatory effects, and reversing the Pb-induced alterations in transmitters and enzymes.

Cardioprotective effects of exercise and curcumin supplementation against myocardial ischemia–reperfusion injury
Sport Sciences for Health | March 2022
Exercise and curcumin individually provided cardioprotective effects against ischemia–reperfusion-induced injury which appears to be associated with an attenuation in mRNA expression of β-amyloid peptide precursor in addition to processing enzymes and an increase in mRNA expression of neprilysin.

Curcumin Inhibits Papillary Thyroid Cancer Cell Proliferation
Analytical Cellular Pathology | March 2022
Curcumin is a polyphenolic compound and a member of the Zingiberaceae (ginger) family derived from turmeric plants. It has been extensively used in Chinese medicine to treat various diseases, including inflammation and cancer. Curcumin was found to participate in the process of pancreatic cancer, colorectal cancer, and hepatocellular cancer by regulating specific lncRNAs and miRNAs. In addition, curcumin can suppress PTC cell metastasis. Curcumin was shown to enhance the anticancer activity of cisplatin in PTC cells and cancer stem-like cells by regulating the JAK/STAT3 signaling. In conclusion, the present study provides evidence that curcumin promotes apoptosis and inhibits proliferation and the Warburg effect by inhibiting LINC00691 in B-CPAP cells. Moreover, the specific molecular mechanism might be mediated through the Akt signaling pathway. This study provides a theoretical basis for the treatment of PTC with curcumin.

Curcumin as an Enhancer of Therapeutic Efficiency of Chemotherapy Drugs in Breast Cancer
International Journal of Molecular Sciences | February 2022
Collectively, curcumin in combination with chemotherapy drugs may improve their clinical application in breast cancer therapy, and it is of considerable value to develop as an adjunct for combination chemotherapy with current drugs to treat breast cancer.  Curcumin is an ideal chemopreventive and chemotherapy agent owning to its multitargeting function on various regulatory molecules, key signaling pathways, and pharmacological safety. This review aimed to elucidate the potential role of curcumin in enhancing the efficacy of doxorubicin, paclitaxel, 5-fluorouracil, and cisplatin via combinational therapy. Additionally, the molecular mechanisms underlying the chemosensitizing activity of these combinations have been addressed. Overall, based on the promising therapeutic potential of curcumin in combination with conventional chemotherapy drugs, curcumin is of considerable value to develop as an adjunct for combination chemotherapy with current drugs to treat breast cancer.

Effects of curcumin supplementation on metabolic parameters, inflammatory factors and obesity values in women with rheumatoid arthritis: A randomized, double-blind, placebo-controlled clinical trial
Phytotherapy Research | February 2022
Curcumin supplementation significantly decreased homeostatic model assessment for insulin resistance (HOMA-IR), erythrocyte sedimentation rate, serum levels of high-sensitivity C-reactive protein and triglycerides, weight, body mass index, and waist circumference of patients compared with the placebo at the end of the study (p < .05 for all). HOMA-IR and triglyceride levels significantly increased within the placebo group.

Curcumin induces autophagic cell death in human thyroid cancer cells
Toxicology in Vitro | February 2022
Curcumin acts as an autophagy inducer on many cancer cells. In the present study, curcumin significantly inhibited the growth of thyroid cancer cells. Autophagy was markedly induced by curcumin treatment as evidenced by an increase in LC3-II conversion, beclin-1 accumulation, p62 degradation as well as the increased formation of acidic vesicular organelles (AVOs). 3-MA, an autophagy inhibitor, partially rescued thyroid cancer cells from curcumin-induced cell death. Additionally, curcumin was found to exert selective cytotoxicity on thyroid cancer cells but not normal epithelial cells and acted as an autophagy inducer through activation of MAPK while inhibition of mTOR pathways.

Effect of Curcumin in Experimental Pulmonary Tuberculosis: Antimycobacterial Activity in the Lungs and Anti-Inflammatory Effect in the Brain
International Journal of Molecular Sciences | February 2022
Curcumin is a natural product with antioxidant, anti-inflammatory and antibacterial activities. Curcumin is a polyphenolic compound obtained from the rhizomes of Curcuma longa, a rhizomatous native plant from South and Southeast Asia that belongs to the family Zingiberaceae. Research has revealed that curcumin has pleiotropic properties, including anti-inflammatory, antioxidant, chemopreventive, chemotherapeutic activity, neuroprotective properties, and antibacterial activity. The pleiotropic actions of curcumin are derived from its complex chemistry and its ability to influence multiple signaling pathways. Curcumin controls the inflammatory response by downregulating the activity of the enzymes cyclooxygenase-2 (COX-2), lipoxygenase, and inducible nitric oxide synthase (iNOS). In addition, curcumin suppresses the activation of nuclear factor kappa B (NF-κB) activation; inhibits the production of the inflammatory cytokines TNF-α, interleukin (IL)-1, -2, -6, -8, and -12, monocyte chemoattractant protein (MCP) and migration inhibitory protein; and down-regulates mitogen-activated and Janus kinases. In addition, curcumin protects the brain from damage through the upregulated expression of the transcription factor, the nuclear factor erythroid 2-related to factor 2 (Nrf2) expression, and the hippocampal levels of brain-derived neurotrophic factor (BDNF). Indeed, there is evidence that curcumin has a beneficial effect on humans suffering from depression and anxiety, linked to curcumin anti-inflammatory effects, dopamine release, antioxidant activity, and neurotrophic factor regulation. Curcumin also resulted in a dose-dependent increase in hippocampal BDNF in a model of depression. These data coincide with our results, where we observed a significant increase in BDNF levels in the hippocampus of animals with TB treated with curcumin,  related to the beneficial effect of curcumin on memory and the decrease in depression-like behavior in this model. Curcumin protected from injury in a model of an ischemic brain through the Akt/Nrf2 pathway. Curcumin has a neuroprotective effect in a model of traumatic brain injury (TBI) associated with activating the Nrf2 pathway. These data suggest that treatment with curcumin has a beneficial effect on various neuroinflammatory and neurodegenerative diseases, including those related to pulmonary TB. This investigation revealed the efficacy of curcumin administration as a novel treatment for controlling neuroinflammation in chronic infectious diseases such as pulmonary TB. In addition, it is worth noting that curcumin had a therapeutic effect on lung disease, indicating that curcumin might be used as a coadjuvant treatment in TB chemotherapy.

Curcumin Ameliorates Cardiac Fibrosis
Frontiers in Pharmacology | February 2022
The therapeutic potential of curcumin has been widely investigated, including its utilization in various of cardiovascular diseases. Curcumin’s health benefits has been well-established, including anti-tumor, anti-viral, anti-oxidative stress, anti-inflammatory, anti-microbial, hypoglycemic etc. Therapeutically, curcumin exhibits promising potential in preclinical as well as clinical studies and is currently in human trials for a variety of conditions, including metabolic syndrome, nonalcoholic fatty liver disease, atherosclerosis, liver cirrhosis, depression, psoriasis, and Alzheimer’s disease (Kocaadam and Şanlier, 2017). The immunomodulatory functions of curcumin arise due to its interactions with cellular and molecular components during inflammatory reactions. Dietary exposure to 40 mg/kg curcumin for 5 weeks showed enhanced IgG levels in rats, suggesting an improvement in immune function after curcumin intervention (South et al., 1997). Curcumin has also been shown to regulate macrophage polarization by increasing the M2 phenotype marker CD163 together with the anti-inflammatory cytokine IL-10 and decreasing the M1 phenotype marker CD86 along with the pro-inflammatory cytokines TNF-α and IL-6 (Li et al., 2017). Curcumin significantly ameliorated the inflammation process subsequent to myocardial infarction, reflected by decreased expression of CD68+ and CD3+ cells, accompanied by dramatically improved cardiac function compared with the placebo group. In addition, cardiac fibrosis is inhibited by curcumin administration. Mechanistically, we discovered that curcumin significantly downregulated pro-inflammatory cytokines in macrophages. Curcumin improves cardiac function and reduces cardiac fibrosis after myocardial infarction. Curcumin has roles in various cardiovascular diseases, including ischemic heart, pressure overload heart, and metabolic disorder-related cardiac diseases. It is well-established that curcumin can directly exerts cardio-protective effect by targeting cardiomyocyte through various of signaling pathway, like disrupts the p300/GATA4 complex and represses agonist-and p300-induced hypertrophic responses in cardiomyocytes (Morimoto et al., 2008)or activates the autophagy by upregulating AMPK and JNK1 to alleviate the apoptosis of cardiomyocytes under ischemic stimulation (Yao et al., 2018).  In summary, our study revealed that the administration of curcumin significantly ameliorated inflammation in the acute phase, as reflected by the promotion of macrophage apoptosis, accompanied by decreased pro-inflammatory cytokine secretion, including IL-6, IL1b, and TNF-α.  These findings suggest that curcumin has potential as a potent therapeutic target in treating adverse remodeling in ischemic heart disease.

Curcumin sensitizes response to cytarabine in acute myeloid leukemia by regulating intestinal microbiota
Cancer Chemotherapy and Pharmacology | February 2022
Curcumin is a natural phenolic compound extracted from curcuma longa, which exerts a wide range of biological effects, such as anti-tumor, anti-inflammatory, anti-oxidation and anti-fibrosis. Moreover, Curcumin was also reported to affect energy metabolism to increase energy expenditure as well as improve insulin sensitivity in obese mice]. Energy metabolism also plays crucial roles in response to chemotherapy. Several studies have reported that targeting energy metabolism could sensitize resistant cells to chemotherapy, such as oxidative phosphorylation inhibitor redirected metabolism toward glycolysis to sensitize resistant cells to cytarabine (Ara-C) in AML.  Curcumin could affect intestinal microbiota to prevent renal failure. Conversely, intestinal microbiota could also enhance the effect of Curcumin in ameliorating HFD-induced obesity by enhancing Ucp1-dependent thermogenesis through regulating bile acids metabolism, suggesting the interaction between intestinal microbiota and Curcumin in curing diseases. Curcumin resulted in strengthening intestinal intact, leading to reduced transfer of bacteria (or their metabolites) to the blood, causing SQLE inhibition. In conclusion, we demonstrated that Curcumin sensitizes response to Ara-C by regulating microbiota and strengthening intestinal intact is promising in chemoresistant therapy.

Curcumin supplementation in the rhesus monkey: effects on cognitive decline and neuroinflammation
Boston University Theses & Dissertations | February 2022
Curcumin, the active ingredient in turmeric, is a polyphenol nutraceutical with potent anti-inflammatory and antioxidative effects. Several ongoing research studies are underway to explore this potential anti-aging compound. Curcumin treatment improved performance on object reversal testing, with treated monkeys making fewer perseverative type errors. We demonstrated that curcumin treatment did affect morphological features of microglia specifically within the while matter. Within the white matter, curcumin treatment was associated with a significant increase in microglial ramification, evidenced by greater process length, number of nodes and convex-hull area and volume. Increased microglial ramification suggests greater likelihood of microglial surveillance within the white matter associated with curcumin treatment. While our findings show the benefit of curcumin supplementation on cognitive performance and its effects on microglial morphology, further study is needed to understand the precise changes that curcumin supplementation may have on inflammation.

Protective Effects of Curcumin in Cardiovascular Diseases—Impact on Oxidative Stress and Mitochondria
Cells | February 2022
In this review, we will highlight the impact of curcumin on age-related cardiovascular dysfunction, adipose tissue, and obesity, as well as its protective effects in atherosclerosis and myocardial infarction. Curcumin can positively affect different risk factors for CVDs and the outcome in the diseases themselves which has been shown in a number of animal models. More importantly, it is effective against cardiovascular diseases and has shown a promising impact on cardiovascular diseases in clinical studies. Already more than 20 years ago, it was shown that piperine, an alkaloid responsible for the pungency of black pepper, dramatically increases the serum levels of curcumin in rats and humans.

A New Perspective on the Treatment of Alzheimer’s Disease and Sleep Deprivation-Related Consequences: Can Curcumin Help?
Oxidative Medicine and Cellular Longevity | February 2022
Curcumin, a natural compound isolated from C. longa, has multiple applications in treatment of various diseases such as cardiovascular diseases, liver disease, obesity, cancer, inflammatory diseases, and aging. Besides these applications and activities, curcumin has been reported to be effective in many neurodegenerative diseases. Studies have shown that curcumin can lead to many improvements in the pathological process of Alzheimer’s disease. Its mechanisms of action can be classified as (I) sustaining homeostasis of the inflammatory system, (II) increasing the clearance of toxic substances from the brain, (III) scavenging free radicals and inducing antioxidant elements, and (IV) binding and limiting aggregation of misfolded proteins. In addition to the effects of curcumin on neurodegenerative diseases, especially Alzheimer’s disease, it has been reported that curcumin can be beneficial in the management of sleep deprivation (SD) and SD-induced neurological consequences as well. The effects of curcumin on the medial prefrontal cortex (mPFC), the protective potential on the dendritic trees from shortening and shedding induced by chronic SD, and the effects of SD-induced memory impairments have been demonstrated by in vivo studies.

Curcumin protects rats against gentamicin-induced nephrotoxicity by amelioration of oxidative stress, endoplasmic reticulum stress and apoptosis
Pharmaceutical Biology | February 2022
Curcumin is a major yellow phenolic pigment of turmeric that is extracted from rhizome of Curcuma longa L. (Zingiberaceae), a spice widely cultivated in tropical countries in south and southeast Asia, such as China, India and Thailand (Wanninger et al. 2015). Numerous studies have shown that curcumin has excellent antioxidant and anti-inflammatory properties. It has the ability to inhibit free radical generation, scavenge ROS and induce an antioxidant response. Moreover, curcumin has also exerted renoprotective effects in several experimental models, including diabetic nephropathy, chronic renal failure, ischaemia and reperfusion; it also combats nephrotoxicity protecting against renal injury from oxidative stress (Trujillo et al. 2013). Interestingly, curcumin  treatment helps protect against acute myocarditis by inhibition of cardiac oxidative and ER stress-mediated apoptosis (Mito et al. 2011).  Curcumin eliminates the hydroxyl radical, superoxide radical, singlet oxygen, nitrogen dioxide and NO (Ruby et al. 1995; Sreejayan and Rao 1997) and has been shown to inhibit hydrogen peroxide induced oxidative injury in a renal cell line (Farombi and Ekor 2006) and prevented reduced activity of antioxidant enzymes including glutathione peroxidase and SOD in rat remnant kidney (Tapia et al. 2012). These results demonstrated that curcumin inhibited oxidative stress and restoration of the antioxidant enzymes leading to improved renal function and rescued kidney damage in GM-induced nephrotoxicity.  These results were in line with the previous report demonstrating that curcumin ameliorated high glucose-induced neural tube defects by suppressing ER stress, caspase activation and apoptosis (Afrin et al. 2015). Moreover, curcumin treatment also prevented cell death induced by H2O2 (Wang et al. 2016). It might be suggested that curcumin attenuated ER stress-induced apoptosis in GM-induced nephrotoxicity, probably associated with the antioxidative activity. The GM-induced nephrotoxicity was contributed by the increasing of oxidative stress, ER stress activation which eventually resulted in the apoptosis cell death. These events were restored by the pre-treatment of curcumin based on its activities to reverse several hallmarks of nephrotoxicity. These findings emphasized the potential therapeutic use of curcumin to be developed as an alternative treatment for nephrotoxicity.

Neuroprotective effects of curcumin on the cerebellum in a rotenone-induced Parkinson’s Disease Model
CNS Neuroscience & Therapeutics | February 2022
Curcumin has a lipophilic property, can pass through cell membranes, and exerts intracellular effects. Curcumin crosses the blood brain barrier  and is also detected in cerebrospinal fluid. The strong antioxidant properties of curcumin scavenge reactive oxygen species and inhibit lipid peroxidation. In one study, administration of curcumin improved behavioral alterations, oxidative damage, and mitochondrial enzyme dysfunction induced by the administration of rotenone in mice. Curcumin also restored electrical activity in the hippocampus altered by rotenone. Curcumin is a strong antioxidant that minimizes oxidative stress in vivo and in vitro. Curcumin exerts various beneficial effects in treating and preventing neurodegenerative diseases, such as stroke and Alzheimer's disease. Additionally, several studies demonstrated curcumin's ability to inhibit key Parkinson's disease-associated features, including ROS formation, apoptosis, cytokine production, oxidative damage, and cognitive impairment in cell lines and experimental animals.  Moreover, Khuwaja et al. demonstrated that curcumin helps stop Parkinsonism and has therapeutic potential. Based on the results of this study, rotenone causes Purkinje cell death and astrogliosis by increasing oxidative stress in the cerebellar cortex. Administration of curcumin prevented these effects. Furthermore, cholinergic neurotransmission alterations induced by rotenone were suppressed by curcumin, thus confirming the behavioral and histological findings. This shows that curcumin attenuated the neurotoxic effects and degenerative histological changes in the cerebellar cortex and alleviated oxidative stress in a Parkinson's disease  rat model. Thus, curcumin could have a role in therapeutic strategies for cerebellar affection related to Parkinson's disease.

Supplements immunologist takes every day to strengthen immune system
CNBC | February 2022
Curcumin is the main active ingredient in turmeric root and has been shown to bestow multiple health benefits. In fact, there are more than 120 human clinical trials showing the effectiveness of curcumin in treating diseases ranging from autoimmunity to Alzheimer’s disease. The magic of curcumin is how it decreases inflammation at multiple levels in the body, not only helping with symptom relief from pain and arthritis but also blocking inflammatory cytokines driving autoimmune disease, heart disease and diabetes. It also improves the health of our gut bacteria, which adds to our overall immune health. Because curcumin is not absorbed well and one would have to eat copious amounts of turmeric root to have significant benefits, I recommend supplementing with 1,000 milligrams per day with food.

Curcumin alleviates hepatic steatosis by improving mitochondrial function in postnatal overfed rats and fatty L02 cells through the SIRT3 pathway
Food & Function | February 2022
It was concluded that postnatal overfeeding damaged mitochondrial biogenesis and antioxidant response, and increased hepatic lipids and the severity of high-fat-induced NAFLD, while curcumin alleviated hepatic steatosis, at least partially, by enhancing mitochondrial function through SIRT3.

Therapeutic Applications of Curcumin in Diabetes: A Review and Perspective
BioMed Research International | February 2022
The curcumin molecule exhibits a multitargeting ability in various pathological conditions, which allows translation into a therapeutic or nutraceutical agent. Curcumin can support balance for oxidative and inflammatory conditions, metabolic syndrome, arthritis, anxiety, and hyperlipidemia. Curcumin has antioxidant, antiamyloid, antimicrobial, antineoplastic, immune-modulating, and neuroprotective effect. Curcumin also showed antidepressant activity through modulating the release of serotonin and dopamine. Diabetics are not able to metabolize well glucose due to defects in insulin secretion and/or action, and curcumin is capable to exert a therapeutic effect playing a critical role on β-cell functions. Several studies have been shown the high therapeutic properties of curcumin in hyperglycemia, diabetic wound healing, diabetic neuropathy, diabetic cardiomyopathy, and diabetic retinopathy and cataract.

Curcumin supplementation in pediatric patients: A systematic review of current clinical evidence
UWA Medical School | February 2022
This systematic review was designed to determine the clinical efficacy and safety of curcumin supplementation for pediatric patients based on clinical trials in children. We systematically searched electronic databases including PubMed, EMBASE, Web of Science, and Scopus for all studies that investigated curcumin administration in the pediatric population without any time frame limitation. Finally, we identified 16 studies for this review. Clinical efficacy and safety of curcumin were assessed in children with inflammatory and immune disorders (including asthma, inflammatory bowel disease (IBD), and juvenile idiopathic arthritis (JIA)), metabolic disorders, autosomal dominant polycystic kidney disease (ADPKD), cystic fibrosis (CF), tetralogy of Fallot (TOF), and infectious diseases. Curcumin was administered in a wide range of doses (45 mg-4,000 mg daily) and durations (2-48 weeks). Overall, curcumin was well tolerated in all studies and improved the severity of inflammatory and immune disorders and metabolic diseases. However, more studies are needed to clarify the role of curcumin supplementation among children with ADPKD, CF, TOF, and infectious diseases.

Effect of curcumin on body mass index and glycemic indices in females with PCOS: a systematic review and meta-analysis of randomized controlled trial
Nutrition & Food Science | February 2022
Random-effects meta-analysis showed significant effects of curcumin on fasting blood sugar (FBS) (−3.62 mg/dl, 95% CI [−5.65, −1.58], p-value < 0.001, I2 = 0.0%), insulin level (−1.67 µU/mL, 95% CI [−3.06, −0.28], p-value = 0.018, I2 = 0.0%) and homeostasis model of assessment insulin resistance (HOMA-IR) (−0.42, 95% CI [−0.76, −0.09], p-value < 0.01, I2 = 0.0%).

A Plethora of Actions of Curcumin - A Magical Agent for Treatment of Wide Range of Diseases Varying from Neuroinflammatory Disease (Alzheimer's disease, Parkinson's disease) IBD to DM and CVD, NAFLD, NASH Along with Various Cancers
Acta Scientific | February 2022
Curcumin has been evaluated for its biological actions: Neuroinflammation; Alzheimer’s disease (AD); parkinson’s disease (PD); antioxidant actions; other anti-inflammatory actions; cardio protection; hepatoprotection in liver fibrosia; non alcoholic fatty liver disease (NAFLD); non alcoholic steatohepatitis (NASH); Anti cancer actions. We observed a total of over 3000 articles and  selected 53 articles for this review with the journals constraints of up to 50 references.  Here we have reviewed in detail the mechanism of action of Curcumin in various above mentioned diseases along with transcription factors involved. Recently even in COVID its use has got documented. In case of cancers, usually it is a good coagent with other chemotherapeutic drugs, might hamper human papilloma virus (HPV) infection as well as avoid cancer cervix generation. In case of NASH, or liver cirrhosis its use with beta blockers might aid in conversion back towards normalcy. Curcumin's pleiotropic actions include inflammatory diseases like cancer, CVD, arthritis, atherosclerosis, DM, gastric disease, inflammatory bowel disease (IBD), psoriasis, HIV etc.  Curcumin is accepted to be a molecule having the capacity to avoid/slowdown the pathological events resulting in age – associated dementia, cognitive decrease, or depression. Additionally, various evaluations have pointed that Curcumin is a potential anticancer treatment in case of human papilloma virus (HPV) infection, in addition to primary as well as malignant squamous cell cancer.

Curcumin Alleviates Dextran Sulfate Sodium-induced Colitis in Mice Through Regulating Gut Microbiota
Molecular Nutrition & Food Research | February 2022
Results showed that oral administration with curcumin relieved macroscopic pathological manifestations, e.g. colon length and histological change. Moreover, it enhanced intestinal barrier via increasing expression of tight junction proteins, e.g. occludin, ZO-1, claudin-3; alleviated DSS-induced intestinal apoptosis via suppressing caspase-3 pathway; mitigated intestinal inflammation via inhibiting the MAPK/NFκB/STAT3 pathway. We also noticed that curcumin is beneficial for modulating abundance of some specific bacteria, including Akkermansia, Coprococcus, Roseburia, and Turicibacter, as well as families such as F16, Enterococcaceae, and Aerococcaceae. Most of the altered bacteria by curcumin are highly correlated with colitis-associated parameters. Curcumin shows therapeutic potential against colitis. It may be served as alternative medicine or adjuvant therapy in the treatment of colitis.

Effectiveness of Curcumin on Outcomes of Hospitalized COVID-19 Patients: A Systematic Review of Clinical Trials
Nutrients | January 2022
The natural spice curcumin has received recent attention in treating diseases involving perturbations of the immune system and inflammation responses, such as COVID-19. Curcumin and other curcuminoids are the main bioactive ingredients of turmeric (Curcuma longa). They have been used for millennia in the traditional medicines of multiple cultures due to their anti-inflammatory, antioxidant, antibacterial, antiviral, antidiabetic, and neuroprotective properties. Curcuminoids have received approval from the USA Food and Drug Administration (FDA), and these compounds have good tolerability and safety. Furthermore, they have already been tested with some successes in clinical trials targeting various diseases. Curcumin treatment—as an adjunct therapy—helps restore the balance between the pro-inflammatory and anti-inflammatory pathways and, at the same time, reduces the persistence of common COVID-19 symptoms and decreases mortality. Together, these findings support curcumin formulations as adjunctive therapy to reduce the hyper-inflammatory effect in COVID-19 patients and improve patient outcomes. Curcumin treatment led to the amelioration of cytokine storm manifestation by reducing pro-inflammatory factors and stimulating anti-inflammatory pathways. Thus, these findings suggest that curcumin treatment may alleviate COVID-19 symptoms by restoration of the pro-inflammatory and anti-inflammatory balance. Furthermore, the study by Pawar et al. showed that curcumin-piperine supplementation led to fewer thromboembolic episodes following recovery from COVID-19 infections.

Cancer Chemoprevention: A Strategic Approach Using Phytochemicals
Frontiers in Pharmacology | January 2022
Curcumin (diferuloylmethane), a polyphenol isolated from Curcuma longa is the most studied phytochemical as a chemopreventive. Curcumin displays a wide variety of pharmacological functions such as anti-inflammatory agent, anti-mutagenic agent, antineoplastic agent, hepatoprotective agent, nutraceutical, anti-microbial agent, anti-oxidant agent, and immunomodulator. It has been shown to have significant roles in prevention, treatment and chemo sensitization of cancer cells (Pavan et al., 2016). Studies have established the anti-proliferative, anti-angiogenic, anti-metastatic, and pro-apoptotic properties of curcumin (Anto et al., 2002; Puliyappadamba et al., 2010; Bava et al., 2011; Vinod et al., 2013). We have reported that curcumin exhibits potential chemopreventive effect against nicotine-induced survival signalling in lung cancer cells. We found that it down-regulates multiple survival signals induced by nicotine in lung cancer cells irrespective of their p53 status (Puliyappadamba et al., 2010). Another study conducted in our laboratory revealed its chemopreventive efficacy against the lung carcinogenesis induced by B (a)P, a potential environmental carcinogen found in cigarette smoke and deep-fried food, in Swiss albino mice (Puliyappadamba et al., 2015). Curcumin treatment has a significant impact on improving the general health of colorectal cancer patients by enhancing expression of p53 molecules in tumour cells and also by promoting the apoptosis of tumour cells (He et al., 2011; Pricci et al., 2020). Curcumin intake causes the down-regulation of NF-kB, COX-2 and phosphorylated STAT3 in peripheral blood mononuclear cells from patients with pancreatic cancer (Dhillon et al., 2008). It has been reported that, daily curcumin intake leads to a significant and dose-dependent reduction in spontaneous ovarian cancer incidence and tumor growth in Hen ovarian cancer model indicating a significant role of curcumin as a chemopreventive strategy for ovarian cancer (Sahin et al., 2018). The administration of curcumin to paediatric patients with relapsed brain tumours undergoing chemotherapy increased their response compared with the controls (Wolff et al., 2012).

Inflammaging and Brain: Curcumin and Its Beneficial Potential as Regulator of Microglia Activation
Molecules | January 2022
Curcumin is a natural compound with a polyphenolic structure. This turmeric extract derives from the rhizome of the Curcuma longa, a member of Zingiberaceae, and shows a wide range of biological and pharmacological activities including antioxidant, anti-inflammatory, antimicrobial, immunomodulatory, and anti-tumor activity. Curcumin is a widely studied polyphenol isolated from Curcuma longa with a variety of pharmacologic properties. It is well-known for its healing properties and has been extensively used in Asian medicine to treat a variety of illness conditions. The number of studies that suggest beneficial effects of curcumin on brain pathologies and age-related diseases is increasing. Curcumin is able to inhibit the formation of reactive-oxygen species and other pro-inflammatory mediators that are believed to play a pivotal role in many age-related diseases. Curcumin has been recently proposed as a potential useful remedy against neurodegenerative disorders and brain ageing. In light of this, our current review aims to discuss the potential positive effects of Curcumin on the possibility to control inflammaging emphasizing the possible modulation of inflammaging processes in neurodegenerative diseases. Curcumin as dietary phenolic compound should be considered as a pharmacological support for longevity, especially in neurodegenerative and neuroinflammatory diseases, due to its activity via declining oxidative stress, modulating signal transduction and gene expression. Curcumin, in fact, is effective as an immune enhancer in modulating systemic inflammation and brain pathologies through multiple communication mechanisms and, for this reason, is hopefully a particularly promising natural agent in counteracting the damages of aging and neurodegenerative diseases. In this respect, the possible interventions by curcumin on microglia suggest the possibility of this natural product to mediate regulation of microglia phenotypes and its functions and also to control redox imbalance and neuroinflammation, thus suggesting a possible use of curcumin as therapeutic agent in preventing and managing major chronic inflammatory disorders typical of the inflammaging process, including brain diseases such as Alzheimer’s disease, Parkinson’s disease, and Multiple Sclerosis. Hence, once again, attention is paid to the modulatory potential of curcumin in its ability to mediate the anti-inflammatory effects and consequently to positively influence immunity and brain aging. Therefore, the use of curcumin as an anti-inflammatory agent with inhibitory effects on microglial transformation could be a valid and promising approach for the treatment of neurodegenerative disorders. Multiple lines of evidence show that the involvement of microglial cells in brain neuroinflammation process typical of aging may be a target for pharmacological interventions. The anti-inflammatory activity of curcumin in microglia is ascribable to the ability of this molecule to inhibit many pro-inflammatory mediators by impeding inflammatory cascades and heightening endogenous anti-inflammatory mediators where curcumin may act as an immunomodulator. In line with what emerges from this review, there is evidence that the combination of standard protocols or new therapies with the use of curcumin-based formulations could be a desirable approach in the containment and treatment of the inflammaging process, including that related to the brain.

The Multifaceted Actions of Curcumin in Obesity
Natural Products and Human Diseases | January 2022
Crcumin, the active ingredient in turmeric, has attracted considerable research interest in tracking down the possible effects in protection against obesity and obesity-related comorbidities. According to the existing literature, curcumin may regulate lipid metabolism and suppress chronic inflammation interacting with white adipose tissue, which plays a central role in the complications associated with obesity. Curcumin also inhibits the differentiation of adipocyte and improves antioxidant properties. In the present review, we sought to deliberate the possible effects of curcumin in downregulating obesity and curtailing the adverse health effects of obesity.

Curcumin and Weight Loss: Does It Work?
International Journal of Molecular Sciences | January 2022
Curcumin is a polyphenolic compound that represents the most important curcuminoid isolated from the rhizome of the plants. It is believed that curcumin possess subtle effects through multiple mechanisms and biochemical targets, collectively leading to substantial health benefits. This indicates that this compound has potential for preventing (and, in the future, treating) obesity. Curcumin has many properties, including antioxidant. The role of antioxidants during the occurrence of oxidative stress is important, which in turn may contribute to the prevention or delay of the development of many diseases (including civilizational) and their possible complications. Therefore, naturally derived antioxidants such as curcumin are of high clinical value. The anti-inflammatory effect of curcumin is equally significant. Curcumin inhibits and regulates tissue production and secretions of pro-inflammatory cytokine, such as interleukins or tumor necrosis factor alpha (TNF-α). Curcumin is a potential anti-cancer agent because of its multidirectional properties with regard to the signaling/molecular pathways. Curcumin possesses the ability to modulate the core pathways involved in cancer cell proliferation, apoptosis, cell cycle arrest, paraptosis, autophagy, oxidative stress and tumor cell motility. Curcumin and Curcuma longa extract inhibit the growth of microorganisms, both G(+) and G(-) bacteria, which often cause human infectious diseases. Curcumin is known to have an antiviral effect; it also has been suggested as a potential treatment option for patients with COVID-19. Curcumin has an anti-diabetic effect through, for example, enhancing glucose uptake and improving pancreatic beta cell function. In addition, curcumin contributes to the reduction of the gluconeogenesis process and to the increase of glucokinase activity. Curcumin was able to restore oxidative stress and DNA methyltransferase functions against diabetic retinopathy. Moreover, curcumin has shown anti-lipidemic effects. There are animal model studies on the use of curcumin in pregnancy. Due to the anti-inflammatory activity of this compound, the possibility of using this compound in the treatment of complications of pregnancy has been suggested, including Gestational Diabetes Mellitus, PreTerm Birth, Preeclampsia and exposure to toxic agents and pathogens. Other activities of curcumin worth mentioning include immune modulation, cardiovascular protection, anti-pulmonary fibrosis, anti-chronic obstructive pulmonary disease and anti-dementia activity. There is a growing scientific interest in curcumin’s therapeutic potential. Indeed, more and more clinical trials based on curcumin administration have been published or are underway. Curcumin is a promising natural bioactive compound which possesses numerous pharmacological activities. It shows multiple mechanism of action and can affect cellular biochemical and physiological regulation. In pharmacies, there are more and more preparations containing curcumin recommended for the prevention of obesity.

Curcumin alleviates restraint stress-induced learning and memory deficit and activity
Behavioral Neuroscience | January 2022
Several investigations have reported that curcumin has a protective effect against stress disturbance. The present study is designed to investigate the effects of curcumin on learning and memory, activity, biochemical, morphology changes, and apoptosis in the hippocampus and prefrontal cortex of restraint stress rats. Curcumin inhibited and reversed the changes of stress induced in the prefrontal cortex and hippocampus of the rats. These findings provided evidence for the protective effect of curcumin therapy on biochemical, morphology, and behavioral changes induced by restraint stress.

Curcumin improves atherosclerosis by inhibiting the epigenetic repression of lncRNA MIAT to miR-124
Vascular | January 2022
Curcumin has protective effect on atherosclerosis. Curcumin suppressed inflammation in atherosclerosis mouse model and ox-LDL-induced cell model. Curcumin relieved ox-LDL-induced cell inflammation. MIAT/miR-124 axis mediated the effect of curcumin on atherosclerosis and altered cell apoptosis and proliferation, both in vivo and in vitro. These data further support the application of curcumin in control of atherosclerosis advancement.

Effect of curcumin supplementation on muscle damage, antioxidant status and inflammatory factors after successive simulated taekwondo competitions
Science & Sports | January 2022
Creatine kinase (CK), lactate dehydrogenase (LDH) and Malondialdehyde (MDA) increased significantly after the competition in placebo group compared to Curcumin supplemented group. Total antioxidant capacity (TAC), significantly increased in Curcumin supplemented compared to placebo group after the competition. Based on the results of this study, Curcumin supplementation has positive effects on reducing muscle damage and oxidative stress.

Curcumin Induces Immunogenic Cell Death In Murine Colorectal Carcinoma
Pharmacological Research | January 2022
Curcumin, a compound found in the rhizome of Curcuma longa, is known to impair the function in cancer cells. This event triggers apoptosis in curcumin-treated cells and can be an important mechanism of the pharmacological effects attributed to curcumin. The present work suggests that curcumin is an inducer of  immunogenic cell death. This observation brings more insights into the mechanism of action of curcumin. It has already been shown that the efficacy of certain cancer therapies, such as anthracycline-based chemotherapy, photodynamic therapy, and radiotherapy, also rely on their ability to reinstate cancer immunosurveillance. Circumventing the immune evasion strategies deployed by cancers and reeducating the host immune system to detect and clear tumor cells can be used as strategies to treat cancer. Thus, the use of curcumin not only to directly kill cancer cells, but also to help inducing an immune response against tumor antigens is an alternative that can be explored in future studies.

Dietary curcumin restores insulin homeostasis in diet-induced obese aged mice
Aging | January 2022
Curcumin is a bioactive polyphenolic compound extracted from the herb Curcuma longa.  Curcumin treatment maintains insulin homeostasis during aging and dietary challenge that is mediated by hepatic IDE. It has antioxidant, anti-inflammatory, and anti-diabetic properties which should mitigate age-associated diseases.  Curcumin supplementation suppresses body weight gain and fat accumulation in aged mice. Its basic mechanism of action as an anti-diabetic therapeutic agent was largely unknown however we previously demonstrated that curcumin supplementation increases insulin sensitivity in hepatocytes by upregulating hepatic IDE expression and preserved islet integrity in a diet-induced obese (DIO) mouse model. Curcumin changes hepatic gene expression profiling and supplementation preserves pancreatic islet integrity in aged mice. Furthermore, we enumerated various cellular and molecular events in the insulin signaling pathway regulated by curcumin.  Dietary curcumin alters gene expression associated with insulin signaling and senescence pathways in the aged mice. In this study, we sought to determine if curcumin supplementation during a nutrient stressor known to cause insulin resistance in aged mice might be beneficial to preserving hepatocytes in an insulin-sensitive phenotype while protecting β -cells from the need to compensate for insulin resistance. In summary, our study illustrates that curcumin supplementation in aged individuals is likely to play a role in mitigating reduced hepatic insulin sensitivity due to aging per se and dietary challenges. It seems convincing that curcumin positively regulates insulin sensitivity in hepatocytes because of the upregulation of IDE that is reflected in reduced demand for increased insulin secretion and synthesis. Thus, curcumin is a potent, natural therapeutic agent which acts in a multifaceted manner to protect aging-induced metabolic disorders.

Nrf2-Related Therapeutic Effects of Curcumin in Different Disorders
Biomolecules | January 2022
Curcumin is a natural polyphenol with antioxidant, antibacterial, anti-cancer, and anti-inflammation effects. This substance has been shown to affect the activity of Nrf2 signaling, a pathway that is activated in response to stress and decreases levels of reactive oxygen species and electrophilic substances. Nrf2-related effects of curcumin have been investigated in different contexts, including gastrointestinal disorders, ischemia-reperfusion injury, diabetes mellitus, nervous system diseases, renal diseases, pulmonary diseases, cardiovascular diseases as well as cancers. In the current review, we discuss the Nrf2-mediated therapeutic effects of curcumin in these conditions. The data reviewed in the current manuscript indicates curcumin as a potential activator of Nrf2 and a therapeutic substance for the protection of cells in several pathological conditions.

Curcumin alters distinct molecular pathways in breast cancer subtypes
Cancer Reports | January 2022
Curcumin is well known for its anticancer properties. Its cytotoxic activity has been documented in several cancer cell lines, including breast cancer. The pleiotropic activity of curcumin as an antioxidant, an antiangiogenic, antiproliferative, and pro-apoptotic, is due to its diverse targets, such as signaling pathways, protein/enzyme, or noncoding gene. Curcumin, a polyphenol extracted from turmeric, is well known for its multifaceted properties like anti-inflammatory, antioxidant, anti-bacterial, anti-malarial, and anticancer. Clinical and preclinical studies have validated the role of curcumin in varied human chronic diseases, including cancer. The therapeutic potential of curcumin can be attributed to its capability to regulate both epigenome and transcriptome. In conclusion, curcumin regulates miRNA and mRNA in a cell type specific manner. Curcumin altered different pathways in breast cancer cell lines such as cell cycle, migration, invasion, and so forth. The integrative analysis led to the detection of miRNAs and mRNAs pairs, which can be used as biomarkers, associated with carcinogenesis, diagnosis and treatment response in breast cancer.

Curcumin exerts a protective effect against obesity and liver injury induced by an atherogenic diet
Functional Foods in Health and Disease | January 2022
Background: Curcumin is a natural yellow polyphenol extracted from the turmeric rhizome (Curcuma longa). Curcumin is known for its potential therapeutic properties as an analgesic, anti-inflammatory, antioxidant, antimicrobial, hepatoprotective, and anti-mutagenic, although some of these biological activities remain unproven. Epidemiological studies have shown a positive relationship between high-fat diets and diet-related chronic diseases. We hypothesized that some adverse effects of consuming atherogenic or high-fat diets can be ameliorated by curcumin supplementation. This study provides supporting evidence to confirm the beneficial effects of curcumin from the point of view of functional food science.

Age-related alterations to working memory and to pyramidal neurons in the prefrontal cortex of rhesus monkeys begin in early middle-age and are partially ameliorated by dietary curcumin.
Neurobiology of Aging | January 2022
Curcumin-treated subjects exhibit better working memory ability and less neuronal excitability. Middle-aged subjects given curcumin exhibited better workng memory performance and less neuronal excitability compared to control subjects. These findings suggest that the appropriate time frame for intervention for age-related cognitive changes is early middle age, and points to the efficacy of curcumin in delaying working memory decline.

Curcumin inhibits the invasion and metastasis of triple negative breast cancer
Journal of Ethnopharmacology | January 2022
Modern pharmacological studies have found that curcumin has many kinds of pharmacological activities of anti-inflammatory, anti-tumor, anti-angiogenesis, anti-metastasis and anti-multidrug resistance. Curcumin has good anti-inflammatory (Lei et al., 2014), anti-oxidation (Santosh et al., 2007), and reducing the levels of ROS(Sethi et al., 2008). It can also inhibit the activation of multiple pathways such as NF-κB (Cho et al., 2007) and IL-1α, IL-6 and other gene expression (Momeni and Eskandari, 2017). A recent study showed that curcumin inhibited the expression of HIF-1 by degrading ARNT in cancer stem-like cells, thereby improving the hypoxia environment and promoting the early apoptosis of breast cancer cells (Sarighieh et al.,2020). Curcumin could significantly reduce cancer proliferation and the expression level of PLAC8 in MCF-7/TAM cells through proteasome and PLAC8/MAPK signaling pathways which showed that curcumin might be a potential adjuvant therapeutic agent for the treatment of tamoxifen-resistant patients (Mao et al.,2021). Moreover, curcumin, as the main ingredient of curry, has no obvious toxic and side effects according to toxicological studies, so it has great potential in the treatment of breast cancer (Lewis and Veltmaat, 2004). Our previous study found that curcumin inhibited the proliferation of breast cancer cells MDA-MB-231 and MCF-7 in vitro and growth of xenograft in vivo. In this study, we found that Gli1 overexpression in MDA-MB-231 adherent cells could promote cell proliferation, invasion and migration, which were inhibited after curcumin and GANT61 treatment. Moreover, curcumin inhibited the formation of mammospheres, and down-regulated the expression of PTCH1,Gli1, Gli2 in Hh pathway in adherent cells, and the expression of E-cadherin, vimentin of EMT genes and Gli1,Gli2, SMO of Hh pathway in MDA-MB-231 mammospheres. In addition, further studies demonstrated that curcumin could inhibit the entry of Gli1 into the nucleus. These data suggested curcumin may inhibit invasion and metastasis of TN breast cancer cells by targeting Gli1. Curcumin can inhibit the proliferation and metastasis of TN breast cancercells, EMT and characteristics of breast cancer stem cells.

Protective Effects of Curcumin in the Reproductive System
Natural Products and Human Diseases | January 2022
The well-known antioxidant natural product curcumin may have properties which could diminish toxic effects. Curcumin has also shown some promise in the cryoprotection of sperm samples through its antioxidant potential.

Curcumin supplementation in pediatric patients: A systematic review of current clinical evidence
Phytotherapy Research | January 2022
Clinical efficacy and safety of curcumin were assessed in children with inflammatory and immune disorders (including asthma, inflammatory bowel disease (IBD), and juvenile idiopathic arthritis (JIA)), metabolic disorders, autosomal dominant polycystic kidney disease (ADPKD), cystic fibrosis (CF), tetralogy of Fallot (TOF), and infectious diseases. Curcumin was administered in a wide range of doses (45 mg–4,000 mg daily) and durations (2–48 weeks). Overall, curcumin was well tolerated in all studies and improved the severity of inflammatory and immune disorders and metabolic diseases. However, more studies are needed to clarify the role of curcumin supplementation among children with ADPKD, CF, TOF, and infectious diseases.

Curcumin Relieves Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior
Behavioral Neurology | January 2022
Curcumin, the major active component extracted from the Chinese medicine Curcuma longa, has been reported to possess neuroprotective effects. Ccurcumin’s potential antidepressant-like effects have been highlighted in many preclinical trials conducted on rats and mice models of depression. Curcumin might be effective as adjunctive treatment in depressive disorders, indicating the promising efficacy of curcumin depression. More and more studies have discussed the potential mechanism of curcumin's antidepressant-like effects. Our previous study found that curcumin could restore changes in proinflammatory cytokines and the indolamine-2, 3-dioxygenase- (IDO-) kynurenine pathway in the hippocampus of CUMS rats, which might ultimately contribute to its antidepressant-like effect. Another study conducted by our teammates Liao et al. suggested that the possible antidepressant-like effects of curcumin are associated with oxidative stress and with changes in the activation of erythroid-2-related factor 2 (Nrf2) in the brain. Moreover, Liao et al. found that curcumin could reverse the decreased expression of BDNF. Other studies have also indicated curcumin’s ability to increase BDNF levels. These studies point strongly to an association between the antidepressant-like effects of curcumin and the regulation of BDNF levels. Curcumin successfully attenuated the abnormal behaviors induced by CUMS and effectively prevented CUMS-induced reduction of PGC-1α, ERRα, FNDC5, and BDNF expressions. Curcumin also enhanced PGC-1α and ERRα translocation from cytoplasm to nucleus. Furthermore, we found that curcumin supplementation effectively promoted neurocyte proliferation and suppressed neuronal apoptosis induced by CUMS. Of note, the PGC-1α inhibitor SR18292 remarkably reversed the beneficial effects of curcumin on depressed rats, indicating an important role of PGC-1α in the antidepressant-like effects of curcumin. Collectively, our data evaluating the neuroprotective action of curcumin in the CUMS rats highlights the involvement of the PGC-1α/FNDC5/BDNF pathway in the antidepressant-like effects of curcumin.

Role of Curcumin in Retinal Diseases—A review
Clinical and Experimental Ophthalmology  | January 2022
Curcumin showed its pleiotropic effects in retinal diseases like diabetic retinopathy by increasing anti-oxidant enzymes, upregulating HO-1, nrf2 and reducing or inhibiting inflammatory mediators, growth factors and by inhibiting proliferation and migration of retinal endothelial cells in a dose-dependent manner in HRPC, HREC and ARPE-19 cells. In age-related macular degeneration, curcumin acts by reducing ROS and inhibiting apoptosis inducing proteins and cellular inflammatory genes and upregulating HO-1, thioredoxin and NQO1. In retinitis pigmentosa, curcumin has been shown to delay structural defects of P23H gene in P23H-rhodopsin transgenic rats. In proliferative vitreoretinopathy, curcumin inhibited the action of EGF in a dose- and time-dependent manner. In retinal ischemia reperfusion injury, curcumin downregulates IL-17, IL-23, NFKB, STAT-3, MCP-1 and JNK. In retinoblastoma, curcumin inhibits proliferation, migration and apoptosis of RBY79 and SO-RB50. Curcumin has already proven its efficacy in inhibiting viral replication, coagulation and cytokine storm in COVID era. Curcumin is a curcuminoid obtained from turmeric (curcuma longa) that belongs to the Zingiberaceae family. They belong to the group of phytocompounds that are biologically active molecules obtained from plants with positive effects on health. Curcumin is a bis-α,β-unsaturated β-diketone with the chemical name 1,7-bis-(4-hydroxy-3-methoxyphenyl)1,6-heptadiene-3,5-dione and commonly called diferuloylmethane, E100 (European code of food additives) or Natural Yellow 3. Its chemical formula is C21H20O6 and molecular weight is 368.38 gm/mol. It has two aromatic ring systems containing o-methoxy phenolic groups that are linked with a seven-carbon linker consisting of α, β-unsaturated β-diketone moiety. It also exists in two tautomeric forms, keto-enol and diketo tautomers. It is present in keto-enol form in polar organic solvents, which is the predominant form of tautomer. Cheng et al. studied the pharmacokinetics, toxicology and biologically effective dose of curcumin in humans with high risk or premalignant lesions. An initial dose of 500 mg once a day in empty stomach in 25 patients and the dose was increased to 1000, 2000, 4000, 8000 and 12,000 if there was no toxicity ≥ grade 2 in at least 3 successive patients. No toxicity was seen in doses up to 8000 mg. Curcumin showed no toxicity up to 8000 mg when taken for 3 months. 

Archived studies and news on curcumin and turmeric
1984 - 2021

 
How may Curcumin effect aging and longevity as an antiaging agent?
Effect of Curcumin on Vascular Aging | Growing evidence indicates curcumin as a promising antiaging agent. The effects of curcumin feeding have been largely investigated in animal models, unanimously reporting a suppression of intermediated oxidative stress and inflammation. By chelating nitrogen dioxide (NO2), curcumin administration in mice significantly attenuates nitric oxide- (NO-) associated vascular endothelial dysfunction and generation of advanced glycation end-products (AGEs), leading determinants of age-related large elastic artery stiffening. As an additional mechanism, curcumin fixes lysosomal membranes and reduces the function of lysosomal acid hydrolases, thus preventing the aberrant deposition of different connective tissue components in aging endothelium. curcumin mitigated hypertrophy in the aging heart via suppression of p300, the global transcription activator. Beneficial effects of curcumin on vascular aging also concern the development of age-related macular degeneration (AMD), one of the most important causes of blindness in elderly. Curcumin remarkably increases the viability of retinal pigment epithelial cells (RPECs) modulating their proliferation apoptosis and OS. Overall, those evidences suggest potential application of curcumin as an innovative approach to AMD, as for other ocular diseases (e.g., ocular dryness, conjunctivitis, uveitis, pterygium, and glaucoma). Even curcumin has been found to prevent the development of cataract in diabetic rats by decreasing AGE accumulation and serum LPO. Curcumin reverses those effects in cultured ECs, whereas in experimental models, prolonged curcumin feeding decreased ROS generation and promoted cerebrovascular endothelium-dependent relaxation, finally leading to improved cerebrovascular function. Neuroprotective effects of curcumin due to UCP2 overexpression suppression especially target hippocampal neurogenesis in the CA1 area, thus affecting spatial learning and memory. Curcumin also prevents detrimental effects of chronic cerebral hypoperfusion by maintaining cholesterol homeostasis. Curcumin also contributes to maintain cholesterol homeostasis, otherwise upset by chronic cerebral ischemia. Indeed, curcumin promotes cholesterol efflux.
Effect of Curcumin on Longevity and Lifespan |  Curcumin was shown to increase the fecundity, reproductive lifespan, and child viability of D. melanogaster. It has been shown that curcumin supplementation of D. melanogaster elevated the developmental duration and longevity of adult Drosophila possibly through epigenetic programming of the pace of life. Curcumin increased longevity was observed in two distinctive strains of D. melanogaste as a result of the delayed expression of aging genes, improved locomotion, and chemoprevention as well. Curcumin was also shown to reduce OS, DNA damage, and number of mutagenic phenotypes induced via high-dose ionizing irradiation. Also, in vivo experiments on curcumin -fed diets (0.5 and 1.0 mg/g of diet) were effective in extending the average lifespan in both females (6.2% and 25.8%, respectively) and males (15.5% and 12.6%, respectively). Also, in C. elegans, curcumin effectively improves lifespan and aging by lowering intracellular ROS and lipofuscin. The effects of curcumin on C. elegans longevity are manifested by body size and pharyngeal pumping rate. This evidence indicates that curcumin would exert its effects independently of the Age-1-DAF-16 pathway but rather through other constituents of the IIS pathway. With regard to cognitive impairment, the in vivo experiment demonstrated that curcumin can improve learning and memory also reducing Aβ plaque formation in the context of Alzheimer disease. D. melanogaster is a promising animal model for research in AD. By increasing amyloid fibril conversion, curcumin reduces the generation of prefibrillar/oligomeric species of Aβ, ultimately protecting against neurotoxicity. The human β-amyloid precursor cleavage enzyme (BACE-1) is another critical enzyme targeted by curcumin in the D. melanogaster model of Alzheimer disease.
Effect of Curcumin on Cell Senescence | The antiaging effect of curcumin does not rely on delayed cellular senescence. As reported by Banji et al., curcumin (40 mg/kg) and piperine (12 mg/kg), especially when combined, counteract D-gal-induced senescence in male Wistar rats by targeting OS and lipofuscin deposition, finally leading to higher hippocampal volume and function with improved spatial memory and serotoninergic signaling. Another study even reported how long-time curcumin therapy may progressively reverse cognitive dysfunction in D-gal-induced senescent mice by delaying the aging process and improving cognitive functions and locomotor activity, as well as restoring the mitochondrial enzyme complex function curcumin. In a recent study, curcumin supplementation rejuvenates senescence-associated changes in thymus among D-gal-induced senescent mice through promotion of proliferating cells, preventing cells from apoptosis, and enhancing the transcription of the autoimmune regulator. Curcumin feeding (50 mg/kg) was also tested in senescence-accelerated mouse prone mice resulting in increased hippocampal SOD activity as well as upregulation of p-calcium/calmodulin-dependent kinase II. Overall, these findings suggest a role of curcumin in improving cognitive difficulties and the expression of hippocampal plasticity-associated proteins. With regard to vascular function, curcumin administration significantly mitigated premature senescence in HUVECs, characterized by a reduction of senescence-related β-galactosidase-positive cells, cell division, levels of senescence-related protein p21 RNA, OS, and apoptosis. Curcumin is also associated with enhanced eNOS phosphorylation and NO generation, in addition to upregulating Sirt1 transcription, translation, and enzymatic activity. In light of these mechanisms, diets containing curcumin  were demonstrated to significantly extend mean lifespan in male C57BL/6 mice and delayed the OS-caused premature senescence. As recently demonstrated, Sirt1 signaling also mediates the anti-inflammatory effects of curcumin in C57BL/6 mice fed with high fat diet in addition to improved myocardial structure and function in streptozocin-induced diabetic mice fed with THC (120 mg/kg/d). Even more recently, it has been hypothesized that the antiaging effect of curcumin may rely on the control of core clock genes. Curcumin treatment in middle aged male Wistar rats restored the phase and daily pulse. Moreover, it has been shown that curcumin mitigated mouse ovarian aging, upgraded embryonic development, promoted oocyte maturation and fertilization via improvement of ovarian hormones, and elevated the amounts of SIRT1 and 3 genes as well as attenuation of aging-associated oxidative stress and cell death. Besides, curcumin can reduce oxidative stress, inflammation status, and lipofuscin deposition in aged rat liver.
 
How may Curcumin work against Neurological and neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, Huntington’s Disease, and cognitive decline or impairment?

Effect of Curcumin on Alzheimer's Disease |  Evidence has accumulated that curcumin has neuroprotective properties and is a candidate for the treatment of Alzheimer’s disease. In an Alzheimer’s disease transgenic mouse, curcumin decreased oxidative stress and repaired amyloid pathology. Antioxidant and anti-inflammatory features of curcumin helped to minimize the manifestation of Alzheimer’s disease, which is characterized by inflammation and oxidation. Recent studies have indicated that curcumin treatment can promote the decomposition of β-amyloid in brain tissues and prevent the aberrant production and accumulation of β-amyloid, which reduces the hyperphosphorylation of tau protein and effectively prevents the degeneration and injury of brain neurons. Curcumin has protective effects for several risk factors of neurodegeneration and is used in the treatment of Alzheimer's disease as well. In vivo studies show the beneficial effects of curcumin on cognition with a dose-dependent manner that higher dosages is more effective as compared to lower dosages. Based on the preclinical findings, curcumin stabilizes/prevents cognitive decline in Alzheimer's disease. A literature review was conducted to verify studies that evaluated the effects of curcumin supplementation on neurodegenerative / psychological disorders such as Alzheimer's and depression in animal and human models, and their respective mechanisms of action. Scholar google, ScienceDirect and PubMed electronic databases were consulted up to September 2021. In the search, the following descriptor combinations were used in the English-language databases: “BDNF”, “Neurogenesis”, “Curcumin BDNF”, “Curcumin Bioavailability”, “Curcumin Depression”, “Curcumin Depression BDNF”, “Curcumin Depression Inflammation”, “Curcumin Serotonin Depression”, “Depression BDNF”, “Depression Brain Size”, “Depression mechanism”, “Depression Medication”, “Depression Neurogenesis”, “Polyphenol Depression”, “Polyphenol Bioavailability”, “Alzheimer's”, “Alzheimer's BDNF”, “Alzheimer's Curcumin”, “Curcumin Alzheimer's BDNF”, “Alzheimer's Inflammation”, “Alzheimer's Oxidation”, "Curcumin Tau protein", "Alzheimer Metals", "Alzheimer Neurogenesis", "Exercise BDNF", "Calorie restriction BDNF ”,“ Omega 3 BDNF ”. In their review, Pluta and colleagues focus on the role and mechanisms of curcumin in inhibiting ischemia/reperfusion brain injury and potential therapeutic strategies in the treatment of ischemic brain damage of the Alzheimer’s disease phenotype. Comparably, Ferreira and colleagues also delineate neuroprotective characteristics by summarizing what is known about the role of curcumin on transthyretin amyloidosis. According to previous reports, curcumin modulates abnormal transthyretin (TTR) aggregation and inhibits its deposition in the tissue. As the gut–brain axis is linked to neurodegeneration, curcumin exerts neuroprotective effect against neurodegenerative disorders by restoring the intestinal barrier function and a healthy gut microbiome. These findings highlight the importance of neuroprotective effect of curcumin against brain damage by regulating both inflammation and oxidative stress. This is consistent with previous findings where curcumin was shown to reduce significantly the mRNA expression of NF-kB and TLR4 and showed protective effects against glutamate neurotoxicity. Studies have shown that curcumin has a therapeutic effect on Alzheimer’s disease by several molecular mechanisms, including decreasing oxidative damage and constraining the creation of the Aβ fibrils in vitro. The anti-inflammation effects of curcumin as a food additive were evaluated in the APPSw mice (Alzheimer-like model) at several doses. The results have indicated that low-dose curcumin (160 ppm) reduced GFAP, which is an astrocytic marker associated with inflammatory processes. Furthermore, the effect of curcumin on spatial memory (an Alzheimer’s disease symptom) in Alzheimer’s disease rat models has shown that curcumin significantly decreases GFAP mRNA in hippocampal astrocytes, which improves the spatial memory in the Alzheimer’s disease rat model. Ambegaokar et al. reported that the inhibition property of curcumin is dose and time-dependent. For example, curcumin concentrations of 15–30 μM are more effective for short trials (<24 h), while its concentrations of 5–15 μM are better suited for longer periods (4–6 days). These data suggest that curcumin may be more effective in preventing AD in low doses if used for long periods. Accumulating data show that Aβ can increase the expression of COX-2, IL-1, and IL-6, while decreasing the peroxisome proliferator-activated receptor-gamma (PPARγ) in amyloid-beta protein precursor transgenic mice, and curcumin can inhibit this function in amyloid-beta-treated astrocytes. Most of the literature about curcumin indicates that this spice has especially strong properties against AD. For instance, the incidence of Alzheimer’s disease among Indian people (who regularly consume these spices) is very low when compared with the reported incidence in Western countries. Only 0.7% of 70–79 years old people in India are affected by AD; however, about 3.1% of Americans in this age range are also affected. Up to now, the potential anti-amyloid therapeutic methods for Alzheimer’s disease treatment have been focused on the amyloid cascade theory, on which the use of Aβ vaccines and metal-complexing agents is based. Strimpakos et al. reported that curcumin has anti-amyloidogenic properties, thus acting against AD-induced Aβ fibrils in vitro and improving cognitive functioning in vivo. Interestingly, another study analyzing the curcumin-mediated neuroprotective effects on brain aging induced by d-galactose in in vitro and in vivo models revealed an anti-aging effect through regulating neuronal loss, apoptosis in D-galactose induced brain aging, and anti-oxidant enzyme expression. Furthermore, curcumin improved neuronal length and cellular senescence down-regulated expression of p16 and p21 and upregulated expression of antioxidant enzymes, including SOD-1, GPX-1, and catalase. Administration of curcumin ameliorated the cognitive impairment and suppressed apoptosis in the cerebral cortex by downregulating Bax and poly (ADP-ribose) polymerase expression and increasing Bcl-2 expression [86]. In neurodegenerative diseases, such as AD, PD, ALS, microglia play an important role by inducing oxidative stress, redox imbalance and neuroinflammation. The activated microglia are represented by M1 (pro-inflammatory) and M2 (anti-inflammatory) functional phenotypes based on the surface molecules and cytokine expression profiles. Different natural products show therapeutic properties on microglia and consequent prevent neurodegenerative diseases; they act by inhibition of microglia polarization and production of inflammatory mediators. In microglia, curcumin acts on different molecular targets. Curcumin inhibited LPS-induced NF-kB and activator protein-1 (AP-1) DNA bindings in BV2 microglial cells decreasing inflammatory mediators. Peroxisome proliferation-activated receptor-γ (PPARγ) is a transcription factor and nuclear receptor protein that regulates inflammatory responses in microglia, astrocytes and when is activated, PPARγ suppresses the production of proinflammatory cytokines and inflammatory pathways by binding the peroxisome proliferator response element. Curcumin activates PPARγ which reduces NF-κB cytokine production in a mouse model of AD, in rat hippocampal primary cell lines and primary astrocytes. Moreover, our group has found that curcumin suppresses LPS induced inflammatory response in microglia cells by down regulation of PI3K/Akt and JAK/STAT/SOCS signaling pathway. In addition, curcumin induces anti-inflammatory mediators, such as HO-1/NRF-2 consequently reducing oxidative stress and neuroinflammation. Curcumin treatment improved neuron loss and degeneration, while also inhibited cellular senescence and oxidative stress by upregulating antioxidant enzyme expression in RA-induced SY5Y cells. In line with the findings described above, the protective effect of curcumin against cognitive impairment has been demonstrated in diabetes mellitus/chronical cerebral hyperperfusion-induced cognitive deficit model. Moreover, curcumin treatment attenuated the neuronal death and suppressed neuroinflammation induced by microglial activation. These protective effects involved the modulation of triggering receptor expressed on myeloid cells 2 (TREM2)/TLR4/NF-kB pathway. Curcumin treatment reduced nod-like receptor protein 3 (NLRP3) dependent pyroptosis. Since NLRP3-dependent pyroptosis has been reported to be involved in the progression of neurodegenerative diseases, this result suggests that curcumin may be useful as pharmacological strategy for neurodegenerative diseases. Further studies are needed for better understanding of curcumin’s promising effects in preventing the neuronal loss and cognition-decline related to aging. The pleiotropic activities of curcumin provide multiple ways to tackle TTR pathophysiology, through direct interaction of curcumin with TTR, or indirect effects affecting signaling pathways associated with TTR amyloid fibril formation and clearance. Bielak-Zmijewska and coworkers summarize scientific data on curcumin’s ability to postpone progression of age-related diseases in which cellular senescence is directly involved. They furthermore point out that curcumin causes elongation of the lifespan of model organisms and alleviates aging symptoms. In addition, they discuss thoroughly curcumin’s ability to modulate cellular senescence. Common brain disorders, including depression and Alzheimer’s disease, have been linked to diminished levels of an important neurologic growth hormone called brain-derived neurotrophic factor. Reports suggest Curcumin has neuroprotective action in Alzheimer’s disease, major depression, epilepsy, and other neurodegenerative disorders. The hippocampus region of brain is associated with memory and cognition. Studies have shown that hippocampus undergoes structural and biochemical changes with normal aging that results in age-related deterioration in hippocampus-dependent cognition. Curcumin has been found to ameliorate age-related memory deficits in aged mice. In elderly, regular curcumin intake improves cognitive function and ameliorates age-related spatial memory deficits. An Australian study, in the Journal of Psychopharmacology in 2015, found that curcumin improved attention and working memory and reduced mental fatigue in older people who took it for four weeks, compared to a placebo. Several studies have shown that curcumin, the active medicinal compound in turmeric, can increase levels of BDNF in the human brain and therefore delay or even reverse a range of common neurological disorders. One of the main drivers of this process is brain-derived neurotrophic factor (BDNF), which is a type of growth hormone that functions in your brain (20). Many common brain disorders have been linked to decreased levels of this hormone, including depression and Alzheimer's disease. Interestingly, curcumin can increase brain levels of BDNF. By doing this, it may be effective in delaying or even reversing many brain diseases and age-related decreases in brain function. It may also improve memory and make you smarter, which seems logical given its effects on BDNF levels. However, controlled studies in people are needed to confirm this. In addition, scientists are beginning to suspect that the neurologic powers of curcumin don’t just stop there, with research suggesting that this compound may improve memory and increase cognitive capacity. Curcumin, thanks to its wide range of effects, seems to help the brain resist buildup of harmful plaque in brains with Alzheimer's.  A study in the Annals of Indian Academy of Neurology explored curcumin's potential for use in the treatment for Alzheimer's disease. Some of the key points included: Curcumin may help the macrophages, which play an important role in our immune system, clear the amyloid plaques found in Alzheimer's disease. Curcumin has anti-proliferative actions on microglia. Microglia are immune cells of the central nervous system that become active in response to any number of stressors on the body. However, if the microglia have been stimulated to react too often, they become hyper-reactive, which can trigger system-wide inflammation that can be difficult to stop. Curcumin has powerful antioxidant and anti-inflammatory properties. "Overall, curcumin decreases the main chemical for inflammation and the transcription of inflammatory cytokines …The exposure to curcumin also impaired the production of pro-inflammatory cytokines (IL-1, IL-6 and TNF-)." As chronic neuro-inflammation is considered one of the major factors in the development of Alzheimer's, it's possible too that curcumin may help in the treatment of other inflammatory disorders. Researchers found that Curcumin not only reduces oxidative damage and inflammation, but also reduces amyloid accumulation and synaptic marker loss and promotes amyloid phagocytosis and clearance. Curcumin worked to prevent synaptic marker and cognitive deficits caused by amyloid peptide infusion and abeta oligomer toxicity in vitro, and may help the immune system clear the brain of amyloid beta, which forms the plaques found in Alzheimer's disease. Clinical trials are in progress at UCLA with Curcumin for Alzheimer's. In the Alzheimer’s Disease Anti-Inflammatory Prevention Trial, researched showed that reducing inflammation has positive effects on patients with Alzheimer’s. Curcumin significantly lowered several inflammation markers, in addition to reducing plaque on the brain (a sign of Alzheimer’s) by 43 to 50 percent. The effect of curcumin (turmeric) on Alzheimer's disease: An overview Neuroprotective activity has also been shown in curcumin. In Alzheimer’s disease (AD), a peptide called β-amyloid (Aβ peptide) aggregates into oligomers and fibrils and forms deposits known as amyloid (or senile) plaques outside neurons in the hippocampus and cerebral cortex of patients. Another feature of AD is the accumulation of intracellular neurofibrillary tangles formed by phosphorylated Tau protein. Abnormal microglial activation, oxidative stress, and neuronal death are also associated with the progression of the disease. Curcumin has been found to inhibit Aβ fibril formation and extension and to destabilize preformed fibrils in vitro. Metal chelation by curcumin might interfere with metal ion (Cu2+/Zn2+)-induced Aβ aggregation. Curcumin might also affect the trafficking of Aβ peptide precursor (APP) and the generation of Aβ peptides from APP. Abnormally activated microglia and hypertrophic astrocytes around amyloid plaques in AD brains release cytotoxic molecules, such as proinflammatory cytokines and ROS, which enhance Aβ formation and deposition and further damage neurons. Curcumin was found to reduce the inflammatory response triggered by Aβ peptide-induced microglial activation and increase neuronal cell survival. When injected into the carotid artery of a transgenic mouse model of AD, curcumin was found to cross the blood-brain barrier, bind to amyloid plaques, and block the formation of Aβ oligomers and fibrils. In other animal models of AD, dietary curcumin decreased biomarkers of inflammation and oxidative damage, increased Aβ peptide clearance by macrophages, dismantled amyloid plaques in the brain, stimulated neuronal cell growth in the hippocampus, and improved Aβ-induced memory deficits. As a result of promising findings in animal models. a few recent clinical trials have examined the effect of oral curcumin supplementation on cognition in healthy older adults and AD patients. A significant reduction in mental fatigue and higher levels of calmness and contentedness following cognitive test sessions were observed in individuals who consumed curcumin (either acutely or chronically) compared to the placebo group. Additionally, the results of cognitive ability tests suggested that curcumin treatment had limited benefits on cognitive function, as shown by better scores in measures of sustained attention and working memory compared to placebo. The results of a six-month trial in 27 patients with AD found that oral supplementation with up to 4 g/day of curcumin - containing all three major curcuminoids - was safe. Curcumin also helps inhibit plaque that research has linked to neuron damage in the brain and a sign of the disease. There may be good news on the horizon because curcumin has been shown to cross the blood-brain barrier. It’s known that inflammation and oxidative damage play a role in Alzheimer's disease, and curcumin has beneficial effects on both. In addition, a key feature of Alzheimer's disease is a buildup of protein tangles called amyloid plaques. Studies show that curcumin can help clear these plaques. Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by the presence of hyperphosphorylated tau protein in neurofibrillary tangles, selective neuronal loss, progressive memory and cognitive impairment (Campbell and Gowran 2007). The molecular pathogenesis of AD involves extracellular deposition of beta-amyloid (Ab) peptides in the hippocampus and curcumin is known to reduce Alzheimer’s pathology (Serafini et al. 2017) possibly due to its anti-aggregatory properties (Cole, Teter, and Frautschy 2007). In a clinical study, curcumin administration (1 or 4 g, 6 months trial) significantly increased the levels of antioxidant vitamin E without inducing any adverse events in patients with AD (Baum et al. 2008). In preclinical studies, curcumin is known to reduce Aboligomer and fibril formation (Yang et al. 2005; Xiong et al. 2011), inhibit the neurotoxicity of Abin the brain (Jiang et al. 2012; Sun, Zhao, and Hu 2013), suppress Ab-induced inflammation (Lim et al. 2001; Lu et al. 2014) and markedly reduce the levels of IL- 1b(Griffin et al. 2006) and inducible nitric oxide synthase (iNOS) (Begum et al. 2008) in transgenic mouse brain. Several studies demonstrated dose-dependent neuroprotective effect of curcumin against Ab-induced toxicity. Curcumin exhibited anti-aggregatory effect against Ab plaque formation by metal chelation (Huang et al. 2004; Tamagno et al. 2005), anti-oxidant effects (Hamaguchi et al. 2009), cholesterol lowering effects (Fassbender et al. 2001; Refolo et al. 2001), inhibition of presenilin-2 and/or by increasing degrading enzymes such as insulin-degrading enzyme and neprilysin (Wang et al. 2014). Curcumin potentiate heat shock proteins production in response to cellular stress, which protects neuronal cells from Ab neurotoxicity and prevent Ab aggregation and accumulation (Scapagnini et al. 2006; Ohtsuka and Suzuki 2000; Cummings et al. 2001).
Effect of Curcumin on Parkinson’s Disease | Dietary curcumin is an important candidate in the prevention or treatment of Parkinson’s disease.  Curcumin is suggested to be an effective therapeutic and nutraceutical agent for Parkinson’s diseasetreatment. Interestingly, curcumin was found to inhibit the synthesis of MOA-B enzyme (Khatri and Juvekar, 2016), which would lead to an increase in the level and availability of DA in the brain. Neuroprotective effects of curcumin in a 6-hydroxydopmin e animal model of Parkinson’s disease (El Nebrisi et al., 2020) indicated an increase in the survival of striatal TH fibers and SNpc neurons, decreased abnormal turning behavior, and exerted neuroprotective properties. These findings provide evidence that α7-nicotinic acetylcholine receptors could be a potential therapeutic target and curcumin would be the first natural source that is found to modulate nicotinic receptors in Parkinson’s disease. Recent evidence indicates decreased superoxide dismutase 1 (SOD1) expression in reactive astrocytes in the damaged substantia nigra, thus leading to inflammation and oxidative stress that contribute to the degeneration of dopaminergic neurons in Parkinson’s disease. Curcumin, through the preservation of SOD1 expression in reactive striatal astrocytes in hemiparkinsonian mice, has anti-inflammatory properties. Gui et al. showed that curcumin, through the inhibition of CYP2E1 (the cytochrome P450 2E1) expression and its activity in reducing ROS and maleic dialdehyde in astrocytes, leads to protection of the mesencephalic astrocytes against LPS-induced toxicities. These results indicate that curcumin could affect the metabolism of several compounds in the CNS and provide evidence for the therapeutic approach in Parkinson’s disease using curcumin at low concentration. Studies show that the oral administration of curcumin (150 mg/kg/day for a week) in mouse models of Parkinson’s disease reversed GFAP and inducible nitric oxide synthase protein expression and also decreased proinflammatory cytokine in the striatum, suggesting that curcumin can improve motor performance in a mouse model of Parkinson’s disease. In addition, curcumin, through the Bcl-2-mitochondria-ROS-inducible nitric oxide synthase pathway, can protect against MPP+ (1-methyl-4-phenylpyridinium)- and MPTP− (1-methyl-4-phenyl-1,2,3,6-tetrahydro­pyridine)-induced apoptosis in PC12 cells. Curcumin can significantly inhibit NF-κβ translocation and activation in astrocytes. In one  study, chronic curcumin administration (50, 100 or 200 mg/kg, p.o., for 3 weeks) significantly ameliorated behavioral alterations like locomotor activity and motor-coordination in mouse model of Parkinson’s disease. In the similar study, curcumin administration reduced oxidative damage and mitochondrial dysfunction in brain homogenate by reducing AChE activity. Curcumin administration decreased malondialdehyde (MDA) and nitrite while increased superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) levels in the brain homogenate of rotenone induced mouse model of Parkinson’s disease (Khatri and Juvekar 2016). It has been demonstrated that curcumin administration alleviate motor dysfunction and increase tyrosine hydroxylase activity in rotenone induced Parkinson’s disease rat model. Curcumin administration phosphorylates Nrf-2 and Akt thereby attenuated oxidative damage of dopaminergic neuron (Cui, Li, and Zhu 2016). Moreover, dietary curcumin supplementation 0.5% or 2.0% (w/w) attenuated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced neurotoxicity in mice via increasing the expression of glial cell line-derived neurotrophic factor and TGF-b1 in nigrostriatal dopaminergic system and thus slowing the progression of Parkinson’s disease (He et al. 2015b). Curcumin administration increased monoaminergic neurotransmitters such as norepinephrine and dopamine in hippocampal homogenate and alleviated hippocampal damage in 6-hydroxydopamine induced Parkinson’s disease in rat. In addition, curcumin treatment upregulated the expression of BDNF, TrkB and PI3K in the hippocampus (Yang et al. 2014). Curcumin treatment (200 mg/kg, for 1 week) significantly attenuated loss of tyrosine hydroxylase, sustained SOD1 level and diminished activation of microglia and astrocytes in the striatum.
Effect of Curcumin on Cognitive Impairment | Curcumin has been reported to improve neuropsychological functions. curcumin has several inhibitory effects on combining aging and Alzheimer’s disease pathophysiology, such as the suppression of amyloid precursor protein (APP) and Aβ synthesis and the overexpression of ApoE and Nrf2 gene, as well as the prohibition of p-mTOR and p-NF-κB. Curcumin prevents D-gal-induced brain aging and cognitive impairment through increments of antioxidant enzymes and inhibition of apoptosis. Beneficial effects of curcumin on mental abilities and functional capacities are associated with a LPO reduction in brain tissue, especially in the hippocampal area. Curcumin improves the redox state in this area and prevents the decline of hippocampal long-term potentiation by maintaining synapse input specificity. Recently, Olesen et al. described that the dysfunction of synaptic mitochondria of the hippocampus causing memory loss during aging. They showed that curcumin feeding significantly improved integration and activity of the synaptic mitochondrial of the hippocampus, inhibiting mitochondrial swelling and enhancing the production of synapses surrounding the mitochondria in mice.
Effect of Curcumin on Multiple Sclerosis and Amyotrophic Lateral Sclerosis | Curcumin was studied to determine if it could help ALS patients, particularly those with bulbar involvement, survive longer (Ahmadi et al., 2018). Curcumin therapy reduced the development of ALS and oxidative damage in a double-blind therapeutic trial (Chico et al., 2018). Recent studies suggest that curcumin, through reduced MMP-9 enzyme activity and decreased release of IL-6 in the astrocyte population of CNS, might beneficially cause anti-inflammatory responses in neurodegenerative diseases, such as multiple sclerosis. Curcumin represents some potential for treatments of various autoimmune diseases related to Th17 cells including MS. Curcumin, through interfering with protein kinase C activity and Ca2+ entry, can eliminate both PMA and thapsigargin-induced ROS generation by the dose-dependent manner. Curcumin can prevent the production of H2O2 and NO; the free radicals produced by macrophages and astrocytes in vitro. In EAE, curcumin has important roles in lymphocyte proliferation inhibition, reductions of IL-17 production by Th17 cells, and Toll-like receptors 4 and 9 (TLR 4 and 9) downregulations. Xie et al. reported that in EAE mice or rats, curcumin shrinks inflammatory cells, including Th17 cells, and hinders its infiltration and differentiation in the CNS. Curcumin has the promising potential for treating multiple sclerosis. Curcumin delivering to the animal models through intraperitoneal injection or oral administration leads to NF-κβ pathway activation decreasing in rat and mouse microglial cell cultures and also in the rat brain. Furthermore, curcumin can also reduce NF-κβ activation in human cell lines and can neutralize ROS in vitro and can stimulate the Nrf2-ARE pathway similarly in the brain and skeletal muscles of mice and also in isolated rat astrocytes. SOD1-misfolded and -aggregated proteins in the motor neurons have an important role in disease pathogenesis, and its targeting treatment can decrease ALS progression in animal models. As previously shown, curcumin can constrain SOD1 aggregation in vitro. Curcumin through gene expression can also stimulate the clearance of the aggregated protein in PALS and Alzheimer’s disease blood cells. Up to the present time, several studies confirm that regimens’ treatment can cause motor neuron enhancement (although there are several different descriptions for these improvements). Furthermore, a small pilot trial revealed some advantage of curcumin in PALS.
Effect of Curcumin on Huntington’s Disease | Studies using established yeast models showed that curcumin inhibits mHTT aggregation, by acting through endosome-sorting complexes required for transport machinery and also destabilizes preformed aggregates. Curcumin, by downregulation of Vps36, a component of the endosome-sorting complexes required for transport-II complex, prevents recruitment of misfolded protein to the perivascular compartment, thus inhibiting the formation of large aggregates. The amyloid-binding ability and anti-amyloid properties of curcumin, along with its ease of oral administration, make it an attractive therapeutic candidate for several neurodegenerative diseases.
 
How may Curcumin work against diabetes?

Because of its anti-inflammatory property, curcumin represents a promising therapeutic option for Type 2 Diabetes. Curcuminoids have been demonstrated in diabetes mellitus type 2 patients to improve insulin resistance, reduce glucose and insulin levels, enhance adiponectin secretion, and lower levels of leptin, resistin, interleukin (IL-6, IL-1β), and TNF-α (Hajavi et al., 2017).  Curcumin and its three derivatives (dimethoxy curcumin, bisdemethoxycurcumin, and diacetyl curcumin) were reported for their antioxidant capabilities (Faizal et al., 2009). Curcumin’s ability to decrease blood sugar levels in human patients was first reported in 1972. A male patient who had diabetes for 16 years ingested 5 g of curcumin over a period, after which his fasting blood sugar decreased from 140 to 70 mg/dl. Ingestion of curcumin along with insulin synergistically reduced the blood sugar level. Furthermore, when the insulin dosage was decreased to the minimum, the anti-diabetic effect of curcumin was persistent. Interestingly, when the ingestion of curcumin and turmeric was discontinued for a week, random blood sugar levels increased to 140 mg/dl. Therefore, ingestion of a daily 5-g dose of curcumin was resumed, which promptly reduced the fasting blood sugar level to 110 mg/dl. Blood urea in this patient after 3 months of turmeric therapy was 20 to 22, and the patient’s electrocardiogram was normal. Turmeric therapy was not associated with any palpable adverse effects; rather, the beneficial effects of turmeric as a good appetite stimulant and effective laxative were observed. More recently, a randomized, double-blind, placebo-controlled clinical trial assessed the efficacy of curcumin in delaying development of Type 2 Diabetes in the prediabetes population.  After 9 months of treatment, 16.4% of participants in the placebo group were diagnosed with  Type 2 Diabetes, whereas none were diagnosed with  Type 2 Diabetes in the curcumin-treated group (Fig. 6a). In addition, the participants of curcumin-treated group showed a better overall function of β cells, with higher HOMA-β and lower C-peptide levels. The curcumin-treated participants also exhibited a lower level of HOMA-IR and higher adiponectin when compared with the placebo group. The authors of this study concluded that the curcumin may be beneficial in a prediabetes population. Curcumin has been shown to equal in effectiveness to the drug metformin in the management of diabetes, but without negative side effects. In the study curcumin was shown to lower blood glucose levels and reverse insulin resistance by suppressing glucose production in the liver. Among those verging on type 2 diabetes, curcumin capsules seem to help stall the onset of the disease. The study that returned these results found that while a little more than 16% of people taking a placebo wound up with a diabetes diagnosis, no one taking curcumin received one. A clinical trial from Thailand, published in Diabetes Care in 2012, found that people with prediabetes who took curcumin for nine months had improved function of insulin-producing cells in the pancreas, along with a significantly reduced risk of developing type 2 diabetes. Other studies suggest that curcumin can improve insulin sensitivity. Another study found curcumin improved metabolic function and reduced the risk of plaque buildup in the arteries of type-2 diabetes patients. Curcumin also acts as an anti-diabetic and antioxidant in patients with type-1 diabetes. Curcumin acts directly on liver cells to help prevent them from becoming fatty, and studies have concluded that Curcumin may have an anti-diabetic effect by decreasing serum fatty acid through the promotion of fatty acid oxidation and utilization. Curcumin also works directly on pancreatic beta cells to help them produce insulin normally. By helping the liver and the pancreas, Curcumin is taking stress off the two most important organs whose function declines before the onset of type 2 diabetes. Curcumin also influences key hormones, supports major body organs, and regulates inflammatory signaling all in ways that help correct or prevent metabolic problems. Curcumin helps lower inappropriately high levels of leptin (reducing leptin resistance) while boosting the all-important levels of the adiponectin (which lowers insulin resistance). Curcumin also helps activate the fat-burning gene signal PPAR gamma, which also helps to make more new, metabolically-fit fat cells. Curcumin directly reduces major inflammatory events from occurring inside white adipose tissue (tumor necrosis factor alpha, interleukin-6, and monocyte chemotactic protein-1). By lowering such inflammation, the source of overweight-induced disease is targeted. Oxidative stress and inflammation have been implicated in the pathogenesis of type 2 diabetes mellitus and related vascular complications. A large body of preclinical evidence suggests that the antioxidant, anti-inflammatory, and glucose-lowering activities of curcumin and its analogs may be useful in the prevention and/or treatment of type 2 diabetes. In a nine-month, randomized, double-blind, placebo-controlled study in 237 subjects with impaired glucose tolerance (pre-diabetes), no progression to overt diabetes was reported with a daily ingestion of a mixture of curcuminoids (0.5 g), while 16.4% of placebo-treated participants developed diabetes. In addition, curcumin supplementation was shown to reduce insulin resistance and improve measures of pancreatic β-cell function and glucose tolerance. Supplemental curcumin was found to be as effective as lipid-lowering drug atorvastatin (10 mg/day) in reducing circulating markers of oxidative stress (malondialdehyde) and inflammation (endothelin-1, TNFα, IL-6) and in improving endothelial function. Another randomized controlled trial also reported that oral curcumin supplementation (1.5 g/day) for six months improved endothelial function, insulin sensitivity, and metabolic markers associated with atherogenesis (plasma triglycerides, visceral fat, total body fat) in participants with type 2 diabetes. Finally, in a two-month randomized, double-blind, placebo-controlled study in 40 individuals with type 2 diabetic nephropathy (kidney disease), daily curcumin ingestion (66.3 mg) significantly reduced urinary concentrations of proteins and inflammation markers (TGF-β, IL-8), suggesting that curcumin might be helpful with slowing the progression of kidney damage and preventing kidney failure. The research on curcumin suggests it can work as a hypoglycemic agent—lowering and helping control blood glucose (blood sugar) levels in people with type 2 diabetes. This can ultimately prevent those with the disease from developing other serious health complications associated with diabetes, such as neuropathy (damage to the nervous system) and nephropathy (kidney disease). A study published in the journal Biochemistry and Biophysical Research Community explored how curcumin might be valuable in treating diabetes, finding that it activates AMPK (which increases glucose uptake) and suppresses gluconeogenic gene expression (which suppresses glucose production in the liver) in hepatoma cells. Interestingly, they found curcumin to be 500 times to 100,000 times (in the form known as tetrahydrocurcuminoids(THC)) more potent than metformin in activating AMPK and its downstream target acetyl-CoA carboxylase. Diabetic neuropathy is a type of neuronal damage, associated with chronic diabetes, characterized by demyelination and deterioration of nerve fibers, alterations in the micro- vasculature and loss of sensory fibers that leads to pain, foot ulcers, amputations, depression, phobias, anorexia, loss of memory and reduction in complex reasoning skills (Patel and Udayabanu 2013).

Curcumin treatment (50 mg/kg, for 8 weeks) upregulated BDNF in frontal cortex and hippocampus alongside reduced oxidative damage in the hippocampus of diabetic db/db mice (Franco-Robles et al. 2014). Curcumin administration significantly increased Na (þ) -K (þ) -ATP activity, reduced lactate dehydrogenase (LDH) activity and lactic acid content as well as stimulates Ca (þ) -Mg (þ) -ATP activity in brain homogenate of alloxan induced diabetic mice. In addition, curcumin administration ameliorated energy metabolism in the brain homogenate of diabetic mice (Miao, Cheng, and Li 2015). Curcumin administration (60 mg/kg, p.o., for two weeks) downregulated the expression of glucose transporter (GLUT) type 3, muscarinic receptor type 3, a7-nicotinic receptor and AChE in brain- stem and cortex of streptozotocin induced diabetic rats. In addition, it reduced the expression level of insulin receptor and choline acetyltransferase in brainstem. Curcumin treatment upregulated the gene expression of choline acetyltransferase, SOD and insulin receptor in cortex. It is known to upregulate the expression level of muscarinic cholinergic receptor 1 in brainstem and cerebral cortex (Kumar et al. 2013) as well as attenuate cognitive deficits in streptozotocin induced diabetic rats (Kumar et al. 2011). Curcumin treatment (60 mg/kg, p.o., for 15 days) downregulated the expression level of dopaminergic D1 and D2 receptor in the cortex. In addition, curcumin administration significantly upregulated dopaminergic D1 receptor and downregulated D2 receptor in the cerebellum of diabetic rodents. Curcumin treatment upregulated phospholipase C and transcription factor cAMP response element-binding protein expression in the cerebellum and cortex of streptozotocin induced diabetic rats resulting in amelioration of emotional and cognitive performance (Kumar et al. 2010). Curcumin administration (60 mg/kg, p.o., for 16 days) upregulated the glutamate decarboxylase while downregulated Bax, caspase 3 and caspase 8 expressions in the cerebral cortex. In addition, curcumin administration attenuated NMDA and AMPA receptor mediated oxidative stress and excitotoxicity in the cerebral cortex of streptozotocin induced diabetic rats (Jayanarayanan et al. 2013). Curcumin supplemented (0.5%) with animal’s diet decreased b-d-glucuronidase activity (Chougala et al. 2012), nitric oxide level, total oxidant status, MDA level and oxidative stress index. Diabetes mellitus, commonly referred to as diabetes, is a chronic metabolic disorder characterized by hyperglycemia, glycosuria, negative nitrogen balance, polydipsia and sometimes ketonemia. In a randomized, double-blind, placebo-controlled trial, oral curcumin extract supplementation (three capsules per day, each curcumin capsule has curcuminoid content of 250 mg) for nine months ameliorated b-cell function, lowered C-peptide and increased homeostasis model assessment-b, reduced insulin resistance and increased the adiponectin level in type 2 diabetic subjects as compared to placebo group (Chuengsamarn et al. 2012). In another clinical study, curcumin administration lowered the level of HbA1c and fasting blood glucose as well as partially reduced LDL-cholesterol and body mass index in diabetic subjects (Rahimi et al. 2016). A recent meta-analysis revealed that, curcumin or combined curcuminoids supplementation effectively lowered the level of fasting blood glucose in individuals with some degree of dysglycemia. In addition, isolated curcumin supplementation significantly decreased HbA1c as compared to placebo and suggested its beneficial role as adjuvant in the treatment of dysglycemic patients (de Melo, Dos Santos, and Bueno 2018). In animal study, curcumin administration is reported to reduce glucose intolerance through induction of glucagon-like peptide-1 secretion. In addition, curcumin administration is known to reduce insulin resistance by downregulating phosphorylation of IRS-1 serine residue and upregulating phosphorylation of IRS-1 tyrosine in the skeletal muscle of rats fed with high fructose. Curcumin treatment also reduced glucose intolerance, hyperinsulinemia and homeostasis model assessment-insulin resistance (HOMA-IR) level. Curcumin treatment decreased C reactive protein and TNF-levels besides downregulated the protein kinase theta (PKCh) and COX-2 protein expressions. Additionally, curcumin significantly downregulated extracellular kinase 1/2 (ERK 1/2) and p38 protein expressions in skeletal muscle. Further, curcumin treatment ameliorated the activity of GPx and attenuated the activation of inflammatory cascades (Maithilikarpagaselvi et al. 2016). Curcumin treatment significantly reduced systolic blood pressure, LDL-cholesterol, triglycerides, aspartate transaminase (AST), alanine transaminase (ALT), total cholesterol, glycemia, total oxidative status, MDA and nitrative stress. A recent study demonstrated that, curcumin administration (100 mg/kg, p.o., daily for 8 weeks) attenuated splenic damage and improved immunity in streptozotocin-induced diabetic rats via antioxidant, anti-inflammatory and anti-apoptotic mechanisms  (Rashid et al. 2017). Curcumin treatment is known to attenuate diabetes and its associated complications like liver disease, adipocyte dysfunctions, pancreatic beta cell dysfunction, vascular dysfunction, nephropathy, neuropathy, retinopathy etc. (Zhang et al. 2013b). In cell culture studies, curcumin treatment suppressed palmitate-mediated insulin resistance, inhibited the ubiquitin-proteasome system, reduced the endoplasmic reticulum (ER) protein aggregation and activated the autophagy signaling in human umbilical vein endothelial cells (Ye et al. 2017). The suggested anti-diabetic mechanisms of curcumin effects are ameliorating b-cell dysfunction, insulin signaling, glucagon like peptide-1 secretion, and reducing glucose intolerance, hyperglycemia, hyperinsulinemia, HOMA-IR level, hyperlipidemia, islet apoptosis and necrosis etc. Therefore, these finding demonstrate that curcumin supplementation in diabetic population may be beneficial.
 
How may Curcumin work against CANCER?

In recent years, in-depth studies of cancer progression have revealed that curcumin suppresses tumors by interfering with all aspects of tumor progression, which is the action of some of the most promising anticancer drugs. First, at the root of cancer progression, curcumin has been shown to elevate the ubiquitination level of TAZ that increases proteasome-degrading TAZ protein, thereby activating the hippo pathway and negatively regulating cancer stem cell function. Additionally, curcumin significantly impedes the self-healing of circulating cancer stem cells, limiting stem cell metastasis. Curcumin also alters the expression of more than 700 genes linked to carcinoma development, such as those involved in DNA recovery or associated with the cell cycle, cell proliferation, or metastasis in NCI-H460 human lung cancer cells. Researchers revealed that curcumin not only changes the expression of many genes, but also alters signaling pathways. Through further investigation, it was found that those curcumin-altered genes induce cell death and control extracellular matrix receptors, repressing NSCLC cell proliferation and migration. These observations indicate that curcumin governs NSCLC tumor growth and exhibits cytotoxic mechanisms at the genetic level. Curcumin possesses various biological activities, such as anticancer effects on various cancers, such as breast, liver, lung, gastric and prostate cancers. The anticancer effects of curcumin have been extensively studied in different cancers, such as breast, lung, colorectal, head and neck, gastric, bladder, prostate, thyroid, liver, ovarian, oral, pancreatic, cervical, tongue and brain cancers. Because of its multitargeting activities, curcumin has exhibited activities against numerous cancer types in human clinical trials. Probably the first indication of curcumin’s anticancer activities in human participants was shownby Kuttan and co-workers, who conducted a clinical trial involving 62 patients with external cancerous lesions. Curcumin was found to produce remarkable symptomatic relief as evidenced by reductions in smell, itching, lesion size, and pain. Kuttan and his colleague’s work was the first to demonstrate curcumin’s anti-cancer potential in both in vitro and in vivo experimental models (Kuttan et al., 1985). Curcumin activates DNA damage response, laying the foundation for the therapeutic use of these nutraceuticals in prostate cancer chemoprevention (Horie, 2012). The general anti-carcinogenic effect of curcumin involves mechanisms like induction of apoptosis and inhibition of cell-cycle progression in rat aortic smooth muscle cells (Chen and Huang, 1998). The antiproliferative effect is regulated partly through hindrance of protein tyrosine kinase activity and c-myc mRNA expression, while the apoptotic effect may partly be mediated via preventing the functioning of protein tyrosine kinase, protein kinase C, and expressions of c-myc mRNA and bcl-2 mRNA (Chen and Huang, 1998). Curcumin inhibits the transcription factor NF-κB (Figure 6) and various downstream gene products like c-myc, Bcl-2, COX-2, nitric oxide synthase (NOS), Cyclin D1, TNF-α, ILs, and matrix metallopeptidase 9 (MMP-9) and has anti-proliferative activities in a diversity of malignancies. Curcumin, either alone or in combination with other agents, has demonstrated potential against colorectal cancer, pancreatic cancer, breast cancer, prostate cancer, multiple myeloma, lung cancer, oral cancer, and head and neck squamous cell carcinoma. Curcumin was found to exert its anticancer activities in many different types of cancer cells by regulating a variety of signaling pathways.  Curcumin induces cell death in numerous animal and human cell lines, including leukemia, melanoma, and carcinomas of the breast, lung, colon, kidney, ovaries and liver. It appears to function by caspase­dependent and independent (mitochondrial) mechanisms, which are associated with the presence and absence of p53. Curcumin has been studied as a beneficial herb in cancer treatment and been found to affect cancer growth, development and spread at the molecular level. Studies have shown that it can contribute to the death of cancerous cells and reduce angiogenesis (growth of new blood vessels in tumors) and metastasis (spread of cancer). Multiple studies indicate that curcumin can reduce the growth of cancerous cells in the laboratory and inhibit the growth of tumors in test animals. There is also evidence that it may prevent cancer from occurring in the first place, especially cancers of the digestive system like colorectal cancer. Curcumin is capable of inhibiting the growth of cancer cells in skin, oral, intestinal, and colon cancers. Animal models show that not only does curcumin block growth of cancer cells in these models, but it also increases the number of cancer-fighting enzymes in the system.  A 2011 study works to quantify the prohibitive properties of curcumin on cancer cells in head and neck squamous cell carcinomas. This type of cancer is the 6th most commonly-diagnosed cancer in the United States. That study showed curcumin not only works as a treatment for squamous cell carcinomas with incredibly promising results, but it has also been shown to demonstrate powerful anti-cancer properties. Part of the excitement surrounding the potential anti-cancer benefits of curcumin revolves around the safety of use of the compound. It is considered pharmacologically safe, which means there are no known drug interactions or specific reactions among patients, making it extremely well-tolerated. For more evidence that turmeric with curcumin in particular being a powerful anti-cancer compound, we need only look at the rates of cancer in parts of the world where turmeric is consumed in higher quantities. Over the years, cancer research has examined the role curcumin plays in treating this disease. Curcumin is antimutagenic as it potentially helps to prevent new cancers that are caused by chemotherapy or radiation therapy used to treat existing cancers. It effectively inhibits metastasis (uncontrolled spread) of melanoma (skin cancer) cells and may be especially useful in deactivating the carcinogens in cigarette smoke and chewing tobacco. Curcumin generates an anticancer effect by inhibiting nuclear factor kappa B (NF-κB), and also reduces the formation of glycation end products which induce inflammation. Curcumin also mediates anticancer activity by targeting many other enzymes/pathways, maintaining levels of vitamins C and E, preventing peroxidation of lipid, and DNA damage. Curcumin targets transformed cells without altering primary astrocytes. It also promotes apoptosis, and shows a synergistic effect in combination cisplatin and doxorubicin drugs. An active constituent of turmeric suppresses carcinogenesis in multiple human carcinomas, which include ovarian cancers, stomach cancer, colon cancer, breast cancer, head and neck cancer. Curcumin suppresses the carcinogenesis by targeting diverse molecular targets of cellular division and apoptosis. The beneficial effects of curcumin on various transcription factors, oncogenes, and signalling proteins are well known. It also targets various stages of carcinogenesis from the initial stage to tumorigenesis, growth, invasion, and metastasis. Animal studies involving rats and mice as well as in vitro studies utilizing human cell lines have demonstrated curcumin's ability to inhibit carcinogenesis at three stages: Tumor promotion, angiogenesis, and tumor growth. In two studies of colon and prostate cancer, curcumin inhibited cell proliferation and tumor growth. The anticarcinogenic effects of turmeric and curcumin are due to direct antioxidant and free-radical scavenging effects and their ability to indirectly increase glutathione levels, thereby aiding in hepatic detoxification of mutagens and carcinogens and in inhibiting nitrosamine formation. A number of laboratory studies on cancer cells have shown that curcumin does have anticancer effects. These studies have found that curcumin can significantly inhibit the growth, development and movement of cancer throughout the body. It seems to be able to kill cancer cells and prevent more from growing. It has the best effects on breast cancer, bowel cancer, stomach cancer and skin cancer cells. An American study that combined curcumin with chemotherapy to treat bowel cancer cells in a laboratory showed that the combined treatment killed more cancer cells than the chemotherapy alone. Another American study seemed to show that curcumin helped to stop the spread of breast cancer cells to other parts of the body. Doctors think that curcumin stays in the digestive system and is absorbed by the cells in the bowel. Several studies have shown that curcumin taken as capsules does get absorbed by the gut and is present in the blood. One of the mechanisms by which it does this is reducing the growth of new blood vessels in tumors (otherwise known as angiogenesis) and can also directly contribute to the death of cancerous cells. Scientists discovered that turmeric is effective in killing cancer cells and also preventing their growth. According to the American Cancer Society, tests indicate that curcumin "interferes with several important molecular pathways involved in cancer development, growth and spread" and has boosted the effects of chemotherapy in animals. Curcumin has the potential for treatment of cancers including colon, breast, prostate, lung, skin and bowel. Curcumin shows a strong ability to kill cancer cells as well as inhibit their growth, boost antioxidant levels and balance the immune system. It seems to work on improving mitochondrial function at a cellular level. Even against drug-resistant strains of leukemia, curcumin caused cell death of cancer cells. Curcumin has been shown to substitute chemotherapy for colorectal cancers, and in multidrug resistant cancers. The ability of curcumin to regulate a variety of signaling pathways involved in cell growth, apoptosis, invasion, metastasis, and angiogenesis in preclinical studies elicited scientific interest in its potential as an anticancer agent in tumor therapy. Curcumin is one of the most powerful and promising chemopreventive and anticancer agents, and epidemiological evidence demonstrates that people who incorporate high doses of this spice in their diets have a lower incidence of cancer. Curcumin's epigenetic modulation has been studied by the US National Cancer Institute (NCI) and academic investigators around the world. Because of low toxicity and great efficacy in multiple in vitro and in vivo cancer models, Curcumin was selected for further development, put through extensive toxicology testing and has successively made it through the first stages (Phase I) of clinical testing abroad and is currently in clinical trials at several sites in the U.S. A phase I clinical trial looked at giving curcumin to 25 patients with pre cancerous changes in different organs. This study seemed to show that curcumin could stop the precancerous changes becoming cancer. Numerous mechanisms have been described for the anticancer activity of Curcumin. Curcumin inhibits the NF-ŒB and STAT3 signaling pathways, which play key-roles in the development and progression of cancer. It inhibits a highly expressed transcription factor Sp-1 and its downstream genes, including ephrin type-B receptor 2 precursor, HDAC4, calmodulin and ADEM10 which serve as an important mechanism to prevent metastasis. Curcumin enhances the expression of several extracellular matrix components and inhibits the phosphorylation of focal adhesion kinase (FAK) and CD24 expression, thus prevents cancer formation, migration and invasion (Vallianou et al. 2015; Shi et al. 2001; Zhou et al. 2013). In addition, the potential mechanism of the anti-invasive effect of curcumin includes downregulation of Akt, EGFR, cyclin D1, cMET and upregulation of DNAJ/heat shock protein (HSP) 40 chaperone. Recent studies revealed that ER stress and autophagy might involve in apoptosis process. Mechanistically, autophagy inhibition could increase curcumin induced apoptosis by inducing ER stress (Vallianou et al. 2015). Further, the anticancer effects induced by phytoconstituent curcumin in malignant cells are mediated via the modulation of multiple signaling pathways and its effectors. Curcumin induced anti-carcinogenic effects includes down-regulation of the insulin-like growth factor type-1 receptor (IGF-1R), EGFR/avian erythroblastosis oncogene B1 (erbB1), erbB2/human epidermal growth factor receptor 2 (HER2), Wnt/b-catenin and sonic hedgehog/glioma associated oncogene (SHH/GLIs), and their respective downstream signaling effectors. Curcumin modulates intra-cellular signal transduction elements such as p21, p27, inhibitor of growth family member 4 (ING4), cyclin D1, c- Myc, VEGF, ICAM-1, MMPS, uPA, COX-2, CXCR-4, Bax, Bad, Bak, Noxa, p53, modulator of apoptosis, caspases etc. resulting in reversal of cancer incidence, progression and relapse (Figure 4) (Jordan et al. 2016; Mimeault and Batra 2011; Kasi et al. 2016). A2012 study indicates that rates of colorectal cancer in India are among the lowest in the developed world. Another study from 2016 shows that Indian women are less likely to be diagnosed with breast cancer, as well. Part of the reason for the lowered cancer rates in India has been attributed to diet, with turmeric and curcumin being major dietary contributors in that part of the world. Combining curcumin with anticancer drugs like gemcitabine in pancreatic cancer, docetaxel in breast cancer, and imatinib in chronic myeloid leukemia may be safe and well tolerated. A recent single-arm, phase II trial combining three cycles of docetaxel/prednisone and curcumin (6 g/day) was carried out in 26 patients with castration-resistant prostate cancer. The level of prostate-specific antigen (PSA) was decreased in most patients and was normalized in 36% of them, and the co-administration of curcumin with drugs showed no toxicity beyond adverse effects already related to docetaxel monotherapy. Many registered phase I/II clinical trials designed to investigate the effectiveness of curcumin alone or with first-line treatment in patients with breast, prostate, pancreatic, lung, or colorectal cancer are under way. Research into preventing cancer: A phase I clinical trial looked at giving curcumin to 25 patients with pre-cancerous changes in different organs. This study showed how curcumin could stop the precancerous changes becoming cancer. A number of laboratory studies on cancer cells have shown that curcumin does have anticancer effects. It kills cancer cells and prevent more from growing. It has the best effects on breast cancer, bowel cancer, stomach cancer and skin cancer cells. A study that combined curcumin with chemotherapy to treat bowel cancer cells in a laboratory showed that the combined treatment killed more cancer cells than the chemotherapy alone. An American study in mice showed that curcumin helped to stop the spread of breast cancer cells to other parts of the body. Doctors think that curcumin stays in the digestive system and is absorbed by the cells in the bowel. Several studies have shown that curcumin taken as capsules does get absorbed by the gut and is present in the blood. A number of activities of curcumin, which are exerted in a chemopreventive and a directly therapeutic manner, indicate that it may be a potential anticancer remedy. Researchers at M.D. Anderson Cancer Center in Houston, TX state that Curcumin has “enormous” potential to prevent and treat cancer. Curcumin was able to suppress tumor formation, growth, and even metastasis according to their review. Currently, there are clinical trials being conducted on the effects of Curcumin on patients with bowel cancer. According to the American Cancer Society, tests have shown that curcumin can kill cancer cells in laboratory dishes, and also slow the growth of the surviving cells. Furthermore, it has been found to reduce the development of several forms of cancer in lab animals, while also shrinking various animal tumors. A review - Anticancer Potential of Curcumin: Preclinical and Clinical Studies - in Anticancer Research concluded that, "…it is quite apparent that curcumin has tremendous potential for prevention and therapy of various cancers." Another study on the role of curcumin in cancer therapy found that,  curcumin is a potent anti-inflammatory agent with strong therapeutic potential against a variety of cancers. Curcumin has been shown to suppress transformation, proliferation and metastasis of tumors, and called for additional and larger controlled studies to determine its full potential. Inhibition of proliferation of tumor cells, induction of apoptosis (a mode of cell death), inhibition of transformation of cells from normal to tumor, inhibition of invasion and metastasis and suppression of inflammation have been linked with the activity of curcumin. Resistance to chemo and radiotherapy is the major reason for cancer relapse. This arises due to the presence of a subpopulation of cancer cells, having self-renewal capabilities called Cancer Stem Cells (CSCs). Studies have confirmed that curcumin could inhibit the breast cancer stem cell population by downregulating the expression of stem cell genes Oct4, Sox2 and Nanog and also the Epithelial-Mesenchymal Transition (EMT) as observed by the down-regulation of mRNA levels of Vimentin, Fibronectin and β-catenin and up-regulation of mRNA levels of E-cadherin (Hu et al., 2019). A combination of sub-optimal dose of 5-FU and curcumin elicits synergistic antitumor potential in murine models as evaluated by a reduction in the tumor-related parameters. Mechanistically, curcumin down-regulates 5-FU induced up-regulation of Thymidylate Synthase (TS), which is responsible for 5-FU chemoresistance (Vinod et al., 2013; Haritha et al., 2021). Another study reported that cervical cancer cells can be sensitized by curcumin to paclitaxel-induced apoptosis through down-regulation of NF-κB, Akt and Bcl2 (Bava et al., 2011). The chemopreventive agent curcumin also act as a potent radiosensitizer in human cervical tumor cells. Curcumin pre-treatment increased reactive oxygen species production and overactivation of the mitogen-activated protein kinase pathway in HeLa and SiHa cells when treated with Ionising Radiation (Javvadi et al., 2008).  Mechanism of action of curcumin mainly involves down-regulation of transcription factor NF-κB by inhibition of Notch signalling, which is involved in cell proliferation, apoptosis, maintenance of stem cell and their renewal. This results in a reduction in expression of NF-κB regulated genes, which includes Bcl-2, cyclin D1 and VEGF (O’riordan et al., 2005). Curcumin is a strong inhibitor of Protein Kinase C (PKC) and several oncogenes such as c-jun, c-fos, c-myc, NIK, MAPKs, ERK, ELK, PI3K, Akt and CDKs. Curcumin also inhibits of the Notch-1 downstream target Hes-1 in esophageal cancer cells. Hes-1 is an important notch signalling target and mediator (Subramaniam et al., 2012). The curcumin analog, 2-pyridylcyclohexanone has also been shown to decreases basal STAT3 phosphorylation and promotes apoptosis in esophageal cancer cell, ESCC cells (Wang et al., 2018). Curcumin quenches free radicals, induces antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase), and up-regulates antioxidative protein markers, Nrf2 and HO-1 that led to the suppression of cellular oxidative stress. In cancer cells, curcumin aggressively increases ROS that results in DNA damage and subsequently cancer cell death (Ak and Gülçin 2008). Curcumin was found to suppress inflammatory cytokines such as IL-6, IL-8, granulocyte macrophage colony stimulatin