why 200 capsules per bottle and 500 mG OF Curcumin 95% per capsule?

HAS THE SAFETY OF CURCUMIN 95% BEEN ESTABLISHED?

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

What is the suggested usage and dosage for curcumin 95%?

"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 do other "curcumin" suppliers use deceptive marketing and misleading advertisements?

November 2024

Curcumin on Human Health: A Comprehensive Systematic Review and Meta-Analysis of 103 Randomized Controlled Trials
Phytotherapy Research | November 2024
Curcumin supplementation can modify fasting blood sugar and some glycemic indices, lipid parameters, as well as inflammatory and oxidative parameters. This updated summary of the accumulated evidence may help inform clinicians and future guidelines regarding medical and scientific interest in curcumin. In total, 103 RCTs on 42 outcomes were included, incorporating a total population of 7216 participants. The credibility of the evidence was rated as high for fasting blood sugar (FBS), C-reactive protein (CRP), high-density lipoprotein (HDL), and weight. The remaining outcomes presented moderate (waist circumference [WC], hip circumference [HC], body mass index [BMI], insulin, Homeostatic Model Assessment for Insulin Resistance [HOMA-IR], quantitative insulin-sensitivity check index [QUICKI], leptin, gamma-glutamyl transferase [GGT], glutathione [GSH], and superoxide dismutase.

Epigenetic influence of curcumin on histone signatures in breast cancer
bioRxiv | November 2024
Curcumin has been shown to suppress breast cancer through the regulation of a multitude of cellular signaling pathways such as cell proliferation, apoptosis, cell-cycle arrest, reactive oxidative stress (ROS), and microRNAs with molecular targets ranging from NF-κB, cyclinD1, P13K, Raf-1, NRF2 and p53. In addition to these mechanisms, curcumin has also been found to influence histone modifications, modulating histone acetylation and methylation in cancer cell lines. For example, in one study on triple-negative breast cancer (TNBC), curcumin was shown to inhibit oncogenic EZH2 by reducing H3K27me3 at the promoter for tumor suppressive DLC1, inducing apoptosis in tumor cells. This is the first study to analyze and profile upwards of 50 histone codes in relation to curcumin in breast cancer and link novel histone PTMs with curcumin treatment. In this study we also found possible connections between curcumin’s epigenetic targets in breast cancer and neurological disorders, suggesting potential common epigenetic pathways utilized by these diseases. Overall, our study elucidated possible new therapeutic targets for curcumin as an epigenetic modulator for breast cancer and other diseases.Curcumin, a natural plant-derived compound, has been shown to have an anticancer effect via its influence on epigenetic regulation.

Curcuma-Based Nutritional Supplements and Risk of Age-Related Macular Degeneration
JAMA Ophthalmology | November 2024
Among patients without a history of Age-Related Macular Degeneration aged 50 years or older, curcumin supplement use was associated with lower rates of developing nonexudative Age-Related Macular Degeneration, advanced nonexudative Age-Related Macular Degeneration or GA, exudative Age-Related Macular Degeneration, blindness, or requiring intravitreal anti-VEGF therapy when compared with matched patients not taking curcumin supplements. Results were consistent among subsets of patients 60 and 70 years or older, respectively. Among patients with early nonexudative Age-Related Macular Degeneration, subsequent instances of curcumin supplement prescription records were associated with lower rates of developing advanced nonexudative Age-Related Macular Degeneration or GA when compared with matched patients with early nonexudative Age-Related Macular Degeneration without a curcumin supplement prescription record. Conclusion and Relevance Results of this cohort study suggest that a reduced risk of developing Age-Related Macular Degeneration or progression to later stages of Age-Related Macular Degeneration was associated with subsequent use of curcumin supplements.

The Best Supplements To Take for Longevity
Health | November 2024
Curcumin is a natural plant compound most notably found in turmeric. It has antioxidant, anti-inflammatory, anti-bacterial, and immune system-boosting properties. Researchers believe curcumin affects the proteins that play a role in the cellular aging processes, including oxidative stress, inflammation, cellular signaling, DNA repair, and apoptosis (death of cells). Curcumin can be taken as a supplement on its own or as a turmeric supplement. Studies have shown that turmeric doses up to 8,000 milligrams daily for up to eight months and curcumin doses up to 8,000 milligrams daily for up to three months are safe.

The effects of curcumin supplementation on inflammatory markers in systemic lupus erythematosus patients: a randomized placebo-controlled trial
European Journal of Nutrition | November 2024
Curcumin supplementation caused a significant reduction in anti-ds DNA and IL-6 levels at the end of the trial in comparison with baseline. Analysis of covariance which was adjusted for confounding variables also revealed that anti-ds DNA and IL-6 levels decreased significantly in curcumin group compared to placebo group by the end of the intervention period. No significant changes were observed in levels of other variables during the study (p > 0.05). Conclusion Curcumin, as an effective and safe adjuvant therapy, ameliorated the autoimmune activity and inflammation in systemic lupus erythematosus patients via reducing anti-ds DNA and IL-6 levels.

Advances in relieving exercise fatigue for curcumin: Molecular targets, bioavailability, and potential mechanism
Journal of Food Science | November 2024
Curcumin, the main naturally occurring bioactive polyphenol in turmeric, has anti-inflammatory and antioxidant properties. There is growing evidence that curcumin can scavenge free radicals, inhibit inflammation, reduce the accumulation of metabolites, and regulate energy metabolism (Fernandez- Lazaro et al., 2020; Hu et al., 2023; Xu et al., 2018). Curcumin regulates gut microbiota through metabolic pathways, providing a new perspective for alleviating fatigue. , curcumin has been shown to interact with a variety of molecular targets (inflammatory cytokines, transcription factors, growth factors, receptors, cell cycle proteins, apoptosis-related proteins, adhesion molecules, and enzymes) through covalent, non-covalent hydropho- bic, and hydrogen bond interactions, providing a number of possible molecular mechanisms (Patel et al., 2020; She- hzad et al., 2017). The anti-inflammatory and antioxidant properties of curcumin are related to its molecular structure and abundant molecular targets. There was evidence that curcumin scavenged free radicals by inducing the acti- vation of the nuclear factor erythroid-2-related factor-2 (Nrf2) signaling pathway (He et al., 2012). Research has shown that curcumin exerts anti-inflammatory effects by binding to pro-inflammatory molecules such as monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α, interleukin-12, IL-8, and IL-6 (Derosa et al., 2016; It can reduce oxidative stress, inhibit inflammation, regulate energy metabolism, and decrease metabolite accumulation by modulating the NF- κB, Nrf2, and AMPK pathways. Therefore, curcumin has the potential to play a variety of positive roles, reduce exercise fatigue, improve exercise performance, and help post-exercise recovery. This review summarized the effects of curcumin on fatigue-related indicators of running and swimming in animals, eccentric muscle movements in humans, running, swimming, and cycling, and Taekwondo training in profes- sional athletes. It was shown that curcumin supplementation can relieve fatigue to a certain extent under different doses, intake times, exercise types, and exercise groups. This confirmed the effectiveness and comprehensiveness of curcumin in alleviating exercise-induced fatigue through the signaling pathway network. Recent studies have also revealed bidirectional interactions between curcumin and the gut microbiota, highlighting the possibility that curcumin alleviates exercise fatigue by improving the icrobial composition and strengthening the intestinal barrier.

Curcumin and Cognitive Function: A Systematic Review of the Effects of Curcumin on Adults With and Without Neurocognitive Disorders
California Institute of Behavioral Neurosciences and Psychology | October 2024
Studies found curcumin significantly improves working memory in the following adult groups: non-demented, metabolically impaired, cognitively impaired, mood impaired, and chemotherapy impaired. Curcumin significantly improved, p <0.01, cognitive performance, verbal memory, and cerebrovascular reactivity, as reflected in changes in blood flow to the brain, which can be measured with various imaging techniques in adults with obesity and prediabetes, indicating benefits for metabolic and cognitive health. Curcumin showed significant improvements, p <0.05, in cognitive and locomotive function as well as a reduction in biomarkers with improved MMSE scores by 15% for adults with pre-existing cognitive impairment and dementia, highlighting its potential for palliative neuroprotection. Curcumin significantly enhanced, p <0.05, cognitive performance scores by 18% and attenuated serum inflammatory biomarkers in adults with major depressive disorder, suggesting curcumin as an adjuvant treatment for depression. Curcumin significantly improved, p <0.05, cognitive function tests with a good safety profile in adults with CICI, supporting the use of curcumin in managing the cognitive side effects of chemotherapy. This systematic review found that curcumin supplementation causes a statistically significant improvement in cognitive performance as well as serum biomarkers for adults age 18 and older with the following characteristics: non-demented healthy adults, adults at risk of or experiencing metabolic disorders, adults with pre-existing cognitive decline, adults with mood disorders, and adults with cognitive chemotherapy side effects. This evidence supports the use of curcumin as a preventive, adjunctive, or alternative therapy for neurocognitive disorders.

Curcumin Inhibits TORC1 and Prolongs the Lifespan of Cells with Mitochondrial Dysfunction
Cells | October 2024
Curcumin stands out as a particularly potent candidate for anti-aging interventions. Curcumin is a polyphenolic compound extracted from the rhizome of Curcuma longa (turmeric), a spice that has been used for centuries in traditional medicine. Extensive research has demonstrated curcumin’s wide-ranging therapeutic potential, including its ability to mitigate the effects of aging and increase lifespan. Curcumin possesses the remarkable capacity to forestall cellular aging, and consequently, extend the PoMiCL of yeast. Our outcomes are consistent with an amount of prior research that has underscored the beneficial effects of curcumin in the context of cellular longevity. Furthermore, our insights into curcumin’s influence on cellular lifespan complement analogous investigations conducted using different genetic backgrounds and distinct cell survival assays. Collectively, these results compellingly advocate for the potential utility of curcumin as a modulator of cellular aging and lifespan extension across diverse eukaryotic species. 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. Mitochondrial dysfunction is a key factor associated with age-related diseases, including cardiovascular diseases, neurodegenerative disorders, sarcopenia, and age-related macular degeneration. We revealed that curcumin not only extends the lifespan of the wildtype but also rescues the shortened lifespan of mitochondrial-defective postmitotic cells during chronological aging in yeast. This finding suggests that curcumin may have therapeutic potential in mitigating the effects of mitochondrial dysfunction, a common hallmark of aging. Our investigation into the mechanisms underlying curcumin’s anti-aging properties revealed that curcumin inhibits TORC1 activity. Curcumin’s ability to inhibit TORC1 activity is crucial for its anti-aging effects, especially in cells with mitochondrial dysfunction. Curcumin enhances mitochondrial function by increasing ATP levels. Curcumin derived from natural sources may have the potential to promote healthy aging and extend lifespan. Second, curcumin’s ability to rescue postmitotic cells with mitochondrial dysfunction highlights its relevance for age-related diseases associated with impaired mitochondrial function. Third, the hormetic response observed with curcumin treatment underscores the importance of dosage and further emphasizes the need for careful consideration when designing interventions. In summary, our study provides valuable insights into the intricate relationship between curcumin, postmitotic cellular aging, TORC1 activity, and mitochondrial function.

Curcumin blunts epithelial-mesenchymal transition to alleviate invasion and metastasis of prostate cancer through the JARID1D demethylation
Cancer Cell International | October 2024
Curcumin, fundamentally a polyphenolic compound, is derived as a powder from the rhizome of the perennial herb, Curcuma longa. Previous studies have shown that curcumin, as a multi-target drug, has anti-inflammatory, antioxidant, anti-infective, anti-fibrotic, and anti-atherosclerotic properties, which could significantly inhibit the occurrence and metastasis of various malignant tumors. In addition, mounting evidence indicates that curcumin can act as an epigenetic regulator to exert anti-tumor effects, improve the expression of histone deacetylases, DNA methyltransferases, and inhibit the invasion and migration of tumors. The results demonstrated that the invasion and metastasis of prostate cancer induced by the knockdown of JARID1D were significantly inhibited by curcumin. Curcumin inhibits the metastatic potential of CRPC cells by regulating AR and EMT-related genes through methylation of JARID1D. These results underscore the therapeutic potential of curcumin in the treatment of invasive prostate cancer. Curcumin, a promising anti-cancer agent, has garnered significant interest for its ability to modulate multiple signaling pathways, thereby inhibiting the proliferation, migration, and invasion of prostate cancer cells. Our investigation revealed that curcumin effectively suppressed the growth of 22RV1 cells at an IC50 of 12.65 µM and enhanced both the expression and demethylation activity of JARID1D at a 14 µM dose. This suggests a capacity of curcumin to upregulate JARID1D expression through demethylation, concurrent with its growth inhibitory effect on prostate cancer cells.  Curcumin can affect the progression of PCa through the PI3K and Wnt signaling pathways [33, 34], but it is more related to the growth and proliferation of prostate cancer cells. In JARID1D mediated invasion and metastasis of PCa, the PI3K and Wnt signaling pathways do not play a dominant role. Both previous report and our study confirm that curcumin may has a DNA demethylation effect on tumor cells. Further experiments demonstrated that curcumin could significantly inhibit the proliferation of PCa cells with different phenotypes Treatment with curcumin significantly inhibited PCa metastasis caused by JARID1D knockdown and decreased the expression of N-cadherin, Vimentin and MMP2, but stimulated the expression of JARID1D, AR and E-cadherin. These results highlight curcumin’s potential to impede prostate cancer invasion and metastasis, particularly when JARID1D is compromised, through the regulation of AR/EMT pathways. In summary, although curcumin has shown certain anti-cancer effects in vitro and animal models, further investigation is required to understand its long-term impact and bioavailability in humans. Furthermore, the administration strategy of curcumin combined with JARID1D agonist may be more beneficial to inhibit prostate cancer metastasis. Our study revealed that the epigenetic modifier JARID1D could restrict the progression of prostate cancer, and curcumin could stimulate the expression level of JARID1D and regulate the transcriptional regulation of AR through demethylation. Taken together, these findings provide the evidence that curcumin has therapeutic potential for invasive PCa, and targeting JARID1D may be a viable therapeutic strategy, particularly in metastatic prevention.

Curcumin suppresses cell viability in breast cancer cell line by affecting the expression of miR-15a-5p
Turkish Journal of Biochemistry | September 2024
The turmeric plant (Curcumin longa) is used to extract curcumin, a hydrophobic and polyphenolic substance with potent anti-cancer effects. There has been an increased interest in research into curcumin’s effect on non-coding RNAs (ncRNA) in cancer. Some essential cell processes, including proliferation, differentiation, and migration, can be altered as a result of epigenetic modifications. ncRNA dysregulation, known to play a key epigenetic regulatory function in the genome, has been associated with a variety of diseases, including cancer. Integrating curcumin and tumor suppressor miRNAs in therapy for cancer may boost bioavailability and lead to greater success in the battle against it. Anti-cancer effects of curcumin have been reported in the literature. The discovery that it can produce this effect by changing the expressions of protein-coding and non-coding RNA molecules has paved the way for new research. In the literature on miR-15a-5p, the effect of which we want to examine in breast cancer in our study, it is stated that curcumin-mediated expression of miR-15a-5p in leukemia cells can be increased, and thus, the expression of the WT1 oncogene can be controlled. Curcumin provides hope in the battle against cancers as research continues to uncover new therapies. Curcumin research is ongoing globally because of its antioxidant and antiviral effects in addition to anti-cancer capabilities. Due to these properties, its importance has been emphasized in the literature not only for cancer but also for many neurodegenerative and metabolic diseases. Curcumin was taken into a clinical phase I trial (NCT03980509) and phase II study (NCT03072992) combined with paclitaxel in BRCA. These clinical phase studies mainly focused on the effects of curcumin on disease recurrence and metastasis. A clinical Phase III trial of curcumin on prostate cancer patients (NCT03769766) is still ongoing. In addition to the idea of using curcumin in combination with various chemotherapeutics, it has been suggested that utilizing it in combination with miRNAs in cancer could strengthen its anti-cancer role. With the discovery of curcumin’s ability to modify miRNA expression, an alternative field for research in cancer-targeted treatment has emerged. In light of the outcomes of our study, we would like to suggest that curcumin’s anti-cancer properties could be strengthened through miR-15a-5p, and a combination of curcumin/miR-15a-5p studies in breast cancer could be more beneficial for cancer therapy.

Exploring the Renoprotective Potential of Bioactive Nutraceuticals in Chronic Kidney Disease Progression: A Narrative Review
Cureus | September 2024
Curcuminoids, including curcumin, demethoxycurcumin, and bisdemethoxycurcumin, are the active compounds found in turmeric. Curcumin's potential mode of action in CKD is by focusing on its effects on endogenous intestinal alkaline phosphatase (IAP). IAP is an enzyme found in the intestines that plays a crucial role in maintaining gut homeostasis and protecting against inflammation and oxidative stress. Curcumin stimulates the production and activity of IAP, leading to beneficial effects in CKD. The activation of IAP by curcumin is suggested to have multiple protective mechanisms, including the reduction of oxidative stress, inflammation, and fibrosis in the kidneys. By enhancing IAP activity, curcumin may help maintain gut barrier integrity and reduce the translocation of toxins and harmful substances into the bloodstream, positively impacting kidney health in CKD patients.

The Effect of Curcumin on Reducing Atherogenic Risks in Obese Patients with Type 2 Diabetes: A Randomized Controlled Trial
Nutrients | August 2024
Curcumin, derived from turmeric root, exhibits notable anti-inflammatory effects. The curcumin intervention significantly reduced pulse wave velocity and improved cardiometabolic risk profiles. These findings suggest that curcumin treatment may effectively reduce atherogenic risks in type 2 diabetes patients with obesity. Curcumin (Curcuma longa), the principal component of the spice turmeric, has recently garnered interest for its potential benefits in addressing various health conditions, notably metabolic syndrome. Research has highlighted the antihypercholesterolemic properties of curcumin extract, including a reduction in cholesterol and triglyceride (TG) levels and decreased vulnerability to low-density lipoprotein cholesterol (LDL-C). The anti-atherosclerotic and protective effects of curcumin against coronary heart disease have also been recognized. Additionally, curcumin has notable potential in managing metabolic diseases due to its anti-inflammatory, antioxidant, and lipid-modifying properties. It enhances insulin sensitivity and supports weight management. Curcumin also protects liver health and offers cardiovascular benefits by reducing inflammation and oxidative stress. These multifaceted effects make it a promising complementary therapy for conditions like obesity, type 2 diabetes, and cardiovascular diseases. Curcumin, a bioactive compound in turmeric, shows potential for reducing atherogenic risk by mitigating inflammation and improving cardiometabolic factors. These effects are promising for protecting against atherosclerosis and related cardiometabolic risks in type 2 diabetes patients with obesity. By reducing cardiometabolic risk factors, curcumin provides various health benefits, making it a valuable component of a balanced diet and healthy lifestyle.

Effect and mechanism of curcumin on colon cancer cell senescence through early growth response 1 (EGR1)
Translational Cancer Research | August 2024
Curcumin inhibited the transcriptional activity of EGR1, thereby promoting cell senescence and inhibiting tumor progression. Curcumin hampers the activity of TF EGR1, affecting the transcription and translation of target genes TERT and SIRT6, thus promoting cell senescence and inhibiting colon cancer cell proliferation. These findings provide potential insights for targeted therapy of colon cancer. Curcumin exhibits diverse anti-tumor properties, including the inhibition of tumor cell proliferation, metastasis, and invasion, rendering it a promising candidate for the prevention and treatment of multiple cancer. Curcumin, a traditional Chinese medicine derived primarily from the rhizome of turmeric, has been identified by modern pharmacological studies as having multiple benefits for the human body, including its anti-inflammatory, anti-tumor, anti-angiogenesis, anti- metastasis, and anti-multidrug resistance activities. Curcumin, a natural compound derived from the turmeric plant, has garnered attention for its potential anticancer properties. Prior investigations have underscored curcumin’s induction of cell senescence across various cancer types, including colon cancer. Our research extends these findings by delineating the mechanism through which curcumin orchestrates the transcription and expression of key genes such as TERT and SIRT6, mediated by EGR1, thereby contributing to cell senescence.The capacity of curcumin to induce cell senescence bears significant implications for treating colon cancer. Senescence cells lose their proliferative potential, thereby impeding tumor growth. Moreover, curcumin has been reported to curb the metastatic propensity of colon cancer cells by stifling epithelial-mesenchymal transition (EMT), a pivotal process in initiating metastasis. Curcumin dampens EGR1 activity and promotes senescence, consequently hindering tumor progression.In conclusion, curcumin mitigates the activity of the TF EGR1, augments the expression of target genes TERT and SIRT6, and accelerates tumor cell senescence. This positions curcumin a potential candidate for colon cancer therapy, offering an alternative approach to clinical treatment. Its ability to inhibit cell proliferation and metastasis underscores its therapeutic potential in colon cancer. Therefore, strategies targeting EGR1 with curcumin may represent a viable option for untreated colon cancer.

Curcumin Induces Autophagy-mediated Ferroptosis by Targeting the PI3K/AKT/mTOR Signaling Pathway in Gastric Cancer
Gastroenterology | August 2024
The polyphenol compound curcumin shows prominent anti-tumor effects in multiple cancer types, including gastric cancer. Curcumin attenuated cell viability but stimulated cell death in gastric cancer cells. Curcumin enhanced autophagy in gastric cancer cells, as demonstrated by the increased levels of ATG5, ATG7, Beclin 1, and LC3B. Besides, curcumin upregulated iron, MDA, GSH, and ACSL4 levels while downregulated lipid ROS, SLC7A11, and GPX4 levels, suggesting its stimulation on ferroptosis in gastric cancer cells. Curcumin decreased p-PI3K, p-AKT, and p-mTOR levels in cells. Importantly, the ferroptosis inhibitor ferrostatin-1 overturned the impacts of curcumin on gastric cancercell viability, death, and ferroptosis. Curcumin suppresses gastric cancer development by inducing autophagy-mediated ferroptosis by inactivating the PI3K/AKT/mTOR signaling. Curcumin has been confirmed to possess anti-oxidant, anticancer, anti-inflammatory, anti-analgesic, lipid-modifier, and anti-microbial effects. Curcumin has previously been reported to suppress tumorigenesis in many types of human cancers by facilitating ferroptosis. In summary, our research confirms that curcumin sup- pressed cell growth but promotes cell death in gastric cancer cells by stimulating ferroptosis. Mechanistically, curcumin induces autophagy and inactivates the PI3K/AKT/mTOR pathway in gastric cancer cells. Hence, curcumin might suppress gastric cancer development by inducing autophagy-mediated ferroptosis by restraining the PI3K/AKT/mTOR signaling. Our observations might expand our knowledge of the effects of curcumin on ferroptosis in gastric cancer and provide a novel direction for the potential use of curcumin in gastric cancer treatment.

Curcumin for COVID-19: 27 studies from 240 scientists and 14,886 patients in 11 countries
C19early.org | August 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.

Evaluation of the effectiveness of curcumin and piperine co-supplementation on inflammatory factors, cardiac biomarkers, atrial fibrillation, and clinical outcomes after coronary artery bypass graft surgery
Clinical Nutrition ESPEN | August 2024
Supplementation with curcumin-piperine had a promising effect on serum CRP and TAC. It also had a favorable impact on CK-MB among patients who underwent CABG surgery.

The Bright Side of Curcumin: A Narrative Review of Its Therapeutic Potential in Cancer Management
Cancers | July 2024
Curcumin, a polyphenolic compound derived from Curcuma longa, exhibits significant therapeutic potential in cancer management. Curcumin demonstrates strong antioxidant and anti-inflammatory properties, contributing to its ability to neutralize free radicals and inhibit inflammatory mediators. Its anticancer effects are mediated by inducing apoptosis, inhibiting cell proliferation, and interfering with tumor growth pathways in various colon, pancreatic, and breast cancers. Curcumin has been used for health maintenance and disease management, dating back to ancient Indian and Chinese medicine over 4000 years ago. In these traditional practices, turmeric, containing curcumin, was used to treat various conditions such as respiratory disorders, liver diseases, anorexia, rheumatism, and diabetic wounds. Curcumin, as highlighted in the literature, holds immense promise in health. Its antioxidant properties enable it to neutralize free radicals and protect cells from oxidative damage, while its anti-inflammatory action inhibits the expression of inflammatory mediators and reduces inflammation at the cellular level. Curcumin has demonstrated neuroprotective effects and potential benefits in treating neurodegenerative diseases. Recent studies have underscored the role of curcumin in reducing brain inflammation, protecting neurons, and promoting neurogenesis. Moreover, numerous studies have illuminated the anticarcinogenic potential of curcumin in various types of cancer, including colon, pancreatic, and other high-risk cancers. Curcumin has been studied for its ability to inhibit tumor cell growth, induce apoptosis, and reduce resistance to chemotherapy and radiotherapy. Curcumin may reverse cancer progression through the inhibition of IL-6R/STAT3. It also sensitizes cancer to antitumor and antimetastatic effects by suppressing the NF-kappa B cell signaling pathway. Therefore, curcumin is an attractive candidate for combination chemotherapy due to its broad spectrum of biological activities. Its anti-inflammatory, antioxidant, and antitumor activities improve the efficacy of conventional chemotherapeutic drugs while reducing side effects. Curcumin may reverse cancer progression through the inhibition of IL-6R/STAT3. It also sensitizes cancer to antitumor and antimetastatic effects by suppressing the NF-kappa B cell signaling pathway. Therefore, curcumin is an attractive candidate for combination chemotherapy due to its broad spectrum of biological activities. Its anti-inflammatory, antioxidant, and antitumor activities improve the efficacy of conventional chemotherapeutic drugs while reducing side effects. In colorectal cancer, curcumin has been shown in vitro to sensitize cancer cells to 5-fluorouracil (5-FU) and oxaliplatin. Studies have shown that curcumin enhances the cytotoxic effects of these drugs by modulating several signaling pathways, including NF-κB and STAT3, leading to increased apoptosis and the inhibition of cell proliferation, migration, and invasion. A synergistic effect in overcoming drug resistance was demonstrated by Howells et al., who found that curcumin enhanced resistance to oxaliplatin chemo induction in both in vitro and in vivo colon cancer cells. Tian et al. showed that curcumin potentiates the antitumor effects of 5-FU in esophageal squamous cell carcinoma cells by downregulating NF-kappa B signaling, leading to increased apoptosis both in vitro and in vivo. Hartojo et al. reported complementary mechanisms of apoptotic pathway activation, stating that the combination of curcumin and cisplatin had an additive effect in inducing apoptosis in esophageal adenocarcinoma cells. Curcumin showed synergistic effects with paclitaxel and doxorubicin in breast cancer cell lines. Farghadani and Naidu, Mohammadian et al., and Vinod et al. found that the combination of curcumin and these chemotherapeutic agents downregulated HER2 and EGFR, which are often overexpressed in breast cancer, inhibited cell proliferation, and induced apoptosis. Curcumin sensitizes breast cancer cells to 5-FU by modulating signaling events involved in cell survival and apoptosis. In clinical trials, patients with advanced breast cancer who received curcumin combined with docetaxel showed higher response rates compared to docetaxel alone. The combination was well tolerated and resulted in fewer side effects. This suggests the potential of curcumin to improve the efficacy of chemotherapy. The combination of curcumin and gemcitabine significantly reduced tumor growth compared to either agent alone in a mouse model of pancreatic cancer. The combination therapy worked by inhibiting angiogenesis and inducing apoptosis by suppressing the NF-κB and COX-2 pathways. Yoshida et al. showed that curcumin can sensitize human pancreatic cancer cells to gemcitabine, potentially overcoming gemcitabine resistance. Treatment with a combination of curcumin and cisplatin significantly reduced tumor size and weight in a mouse xenograft model of ovarian cancer. The combination therapy was more effective than either agent alone. Also, it attenuated cisplatin-induced nephrotoxicity, highlighting curcumin’s protective role against chemotherapy’s side effects. A phase II clinical trial in patients with metastatic colorectal cancer showed that adding curcumin to the standard FOLFOX regimen (5-FU, leucovorin, and oxaliplatin) improved overall survival and progression-free survival compared to the standard regimen alone. Therefore, combining curcumin with chemotherapeutic agents in vitro and in vivo has shown a synergistic effect in cancer therapy. In summary, curcumin demonstrates substantial therapeutic potential in cancer treatment due to its multifaceted biological activities, including antioxidant, anti-inflammatory, and anticancer properties, exerting its potential therapeutic effects against various types of cancer. For example, curcumin exhibits substantial anticancer properties particularly against gastrointestinal cancers, such as colorectal and pancreatic cancer, by inducing apoptosis, inhibiting cell proliferation, and modulating multiple cell signaling pathways. Additionally, studies have shown promising results in the treatment of breast cancer, where curcumin interferes with cancer cell growth and metastasis. The compound has also demonstrated efficacy in prostate cancer by targeting androgen receptor signaling and in head and neck cancers through the inhibition of tumor growth and angiogenesis

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.

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