Efficacy and safety of curcumin therapy for knee osteoarthritis: A Bayesian network meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcumin, a polyphenolic compound extracted from turmeric (Curcuma longa L.), is widely used in traditional Chinese medicine to treat osteoarthritis and rheumatoid arthritis. Clinical and experimental studies show that curcuminoid formulations have considerable clinical application value in the treatment of knee osteoarthritis (KOA). AIM OF THE STUDY: To evaluate the efficacy and safety of curcumin, both alone and in combination with other drugs, in KOA treatment through a Bayesian network meta-analysis (NMA). METHODS: We searched PubMed, Embase and Cochrane Library for randomized controlled trials of curcumin for KOA treatment. The time range of the search was from the establishment of each database to April 26, 2023. The NMAs of outcome indicators were all performed using a random-effects model. NMAs were calculated and graphed in R using MetaInsight and Stata 140 software. Measurement data were represented by the mean difference (MD), while count data were represented by the odds ratio (OR); the 95% confidence interval (CI) of each effect size was also calculated. RESULTS: This study included 23 studies from 7 countries, including 2175 KOA patients and 6 interventions. The NMA results showed that compared with placebo, curcumin significantly reduced the visual analogue scale pain score (MD = -1.63, 95% CI: -2.91 to -0.45) and total WOMAC score (MD = -18.85, 95% CI: -29.53 to -8.76). Compared with placebo, curcumin (OR = 0.17, 95% CI: 0.08 to 0.36), curcumin + NSAIDs (OR = 0.01, 95% CI: 0.00 to 0.13) and NSAIDs (OR = 0.11, 95% CI: 0.02 to 0.47) reduced the use of rescue medication. Compared with NSAIDs, curcumin (OR = 0.51, 95% CI: 0.25 to 0.94) and curcumin + NSAIDs (OR = 0.23, 95% CI: 0.06 to 0.9) 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 KOA treatment. CONCLUSIONS: Curcumin, either alone or in combination with other treatments, is considered to have good clinical efficacy and safety in KOA treatment. Drug combinations containing curcumin may have the dual effect of enhancing efficacy and reducing adverse reactions, but this possibility still needs to be confirmed by further clinical and basic research.

Curcumin exerts protective effects on the thyroid gland in propylthiouracil-treated rats.

INTRODUCTION: Among the plant ingredients, some compounds interfere with the functions of the thyroid gland. However, there is limited research on the effect of curcumin (CMN) on the functions of this gland. The aim of this study was to analyze the effect of CMN on morphology, histochemical reactivity of cytochrome c oxidase (CCO) and secretion functions of the thyroid gland under conditions of hypothyroidism induced by propylthiouracil (PTU). MATERIAL AND METHODS: The rats were treated for 30 days by gavage with CMN (100 mg/kg b.w.) and/or PTU (1 mg/kg b.w.). Control rats received vehicle only. Histomorphometric tests were performed on the thyroid glands, cytochrome c oxidase activity was visualized using the histochemical method, and the levels of thyroid hormones were measured using the radioimmunoassay method. RESULTS: Rats receiving PTU showed compensatory changes in their thyroid glands, including a significant increase in thyroid epithelium height, a decrease in colloid volumen density, a decrease in the percentage of small follicles, an increase in medium-sized follicles compared to the control group, as well as a significant increase in CCO histochemical reactivity in the columnar epithelium and a decrease in FT4 serum level compared to the control group. The administration of CMN reversed these adverse changes caused by PTU. The PTU + CMN group exhibited a significant decrease in the height of the thyroid follicle epithelium compared to the PTU group. The percentage of small and medium-size follicles in the CMN + PTU group did not differ from the control group. Furthermore, CCO reactivity in the cubic epithelium and serum FT4 levels increased compared to the PTU group. Administration of CMN alone resulted in a significant increase in FT4 levels compared to the control group. CONCLUSIONS: The administration of CMN to rats with induced hypothyroidism resulted in a reduction of hyperplasia, hypertrophy, and increase in secretory activity of the thyroid gland. These findings suggest the protective effect of CMN against induced hypothyroidism.

Curcumin interrupts leptin-regulated microRNA-122 in hepatic stellate cells in vitro and in vivo.

The purpose of this study was to evaluate the effect of curcumin, an active polyphenol, on the leptin induced lowering of miR-122 in Hepatic stellate cells (HSCs) in vivo and an animal model. Gene expression was evaluated by transfection assay, real-time PCR, or Western blot analysis. The liver fibrosis model of leptin deficient mouse was used for in vivo experiment. As a result, curcumin showed inhibitory effect on leptin induced lowering of the miR-122 in HSCs. Curcumin suppressed leptin induced sonic hedgehog (Shh) expression and blocked leptin induced Shh signaling pathway, which was essential for curcumin inhibition of the negative role of leptin in miR-122 expression in HSCs. The influence of curcumin on the negative effect of leptin on miR-122 level was followed by the attenuation of liver fibrosis caused by leptin in leptin-deficient mouse model. In conclusion, curcumin could reduce the decrease of miR-122 level in HSCs induced by leptin and inhibit liver fibrosis induced by leptin. These data may have potential implications to treat with liver fibrosis by elevating the expression of leptin in humans especially obese patients.

Anti-inflammatory activity of curcumin in a model of L-arginine-induced acute pancreatitis in rats.

BACKGROUND: Acute pancreatitis (AP) is a pathology characterized by activated digestive enzymes to digest pancreatic tissue and inflammation. This study aimed to investigate the effect of curcumin, which has antioxidant and anti-inflammatory properties, on AP and its effectiveness at different doses. METHODS: Forty Sprague Dawley albino male rats, 12 weeks old, weighing 285-320 g, were used in the study. The rats were divided into control, curcumin, AP, low (100 mg/kg), and high (200mg/kg) dose curcumin groups. An experimental pancreatitis model was created with 5 g/kg L-arginine and samples (amylase, lipase, IL-1ß, IL-6, TNF-alpha, CRP, histopathological) were taken after 72 hours. RESULTS: There was no difference between the groups in terms of the weight of the rats (p=0.76). In the AP group, it was observed that the experimental pancreatitis model was successfully created after examination. Laboratory and histopathological examination results in the curcumin-administered groups were regressed compared to the AP group. The decrease in laboratory values was higher in the high-dose curcumin group than in the low-dose (p<0.001). CONCLUSION: Laboratory and histopathological changes occur in AP according to clinical severity. The antioxidant and anti-inflammatory effects of curcumin are known. In the light of this information and according to the results of our study, it has been shown that curcumin is effective in the treatment of AP, and the effect of curcumin increases with the dose increase. Curcumin is effective in treating AP. However, while high-dose curcumin was more effective in inflammatory response than low-dose, it showed similar histopathological results. KEY WORDS: Acute, Curcumin, Cytokines, Inflammation, Pancreatitis.

Efficacy and safety of curcumin in diabetic retinopathy: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic retinopathy (DR) is one of the most common complications of diabetes and has become a major global cause of blindness. Curcumin, an extract of Curcuma longa (turmeric), is effective in preventing and treating diabetes. Recent studies have shown that curcumin can delay DR development. However, there has been no systematic review of its treatment of DR. This study will conduct a systematic review and meta-analysis of currently published randomized controlled trials (RCT) of curcumin for treating DR patients to evaluate its efficacy and safety. METHODS: We will search the relevant studies of curcumin in the treatment of DR in PubMed, Medline, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang databases from their respective inception dates to May 2022. A meta-analysis of the data extracted from qualified RCTs will be conducted, including the progression of DR, visual acuity, visual field, macular edema, quality of life, and adverse events. The meta-analysis will be performed using Review Manager 5.4.1 software, and the results will be based on either random-effects or fixed-effects models, depending on the heterogeneity. The Grading of Recommendations, Development, and Evaluation (GRADE) system will be used to evaluate the reliability and quality of evidence. RESULTS: The results of this study will provide sound and high-quality evidence for the efficacy and safety of curcumin in the treatment of DR. CONCLUSION: This study will be the first meta-analysis to comprehensively assess the efficacy and safety of curcumin in the treatment of DR and will provide helpful evidence for the clinical management of this disease. SYSTEMATIC REVIEW REGISTRATION: INPLASY202250002.

Curcumin-dependent phenotypic transformation of microglia mediates resistance to pseudorabies-induced encephalitis.

Pseudorabies virus (PRV) causes viral encephalitis, a devastating disease with high mortality worldwide. Curcumin (CUR) can reduce inflammatory damage by altering the phenotype of microglia; however, whether and how these changes mediate resistance to PRV-induced encephalitis is still unclear. In this study, BV2 cells were infected with/without PRV for 24 h and further treated with/without CUR for 24 h. The results indicated that CUR promoted the polarization of PRV-infected BV2 cells from the M1 phenotype to the M2 phenotype and reversed PRV-induced mitochondrial dysfunction. Furthermore, M1 BV2 cell secretions induced signalling pathways leading to apoptosis in PC-12 neuronal cells, and this effect was abrogated by the secretions of M2 BV2 cells. RNA sequencing and bioinformatics analysis predicted that this phenotypic shift may be due to changes in energy metabolism. Furthermore, Western blot analysis showed that CUR inhibited the increase in AMP-activated protein kinase (AMPK) phosphorylation, glycolysis, and triacylglycerol synthesis and the reduction in oxidative phosphorylation induced by PRV infection. Moreover, the ATP levels in M2 BV2 cells were higher than those in M1 cells. Furthermore, CUR prevented the increase in mortality, elevated body temperature, slowed growth, nervous system excitation, brain tissue congestion, vascular cuffing, and other symptoms of PRV-induced encephalitis in vivo. Thus, this study demonstrated that CUR protected against PRV-induced viral encephalitis by switching the phenotype of BV2 cells, thereby protecting neurons from inflammatory injury, and this effect was mediated by improving mitochondrial function and the AMPK/NF-κB p65-energy metabolism-related pathway.

Sensitization of GSH synthesis by curcumin curtails acrolein-induced alveolar epithelial apoptosis via Keap1 cysteine conjugation: A randomized controlled trial and experimental animal model of pneumonitis.

INTRODUCTION: Epidemiological studies have reported an association between exposures to ambient air pollution and respiratory diseases, including chronic obstructive pulmonary disease (COPD). Pneumonitis is a critical driving factor of COPD and exposure to air pollutants (e.g., acrolein) is associated with increased incidence of pneumonitis. OBJECTIVES: Currently available anti-inflammatory therapies provide little benefit against respiratory diseases. To this end, we investigated the preventive role of curcumin against air pollutant-associated pneumonitis and its underlying mechanism. METHODS: A total of 40 subjects was recruited from Chengdu, China which is among the top three cities in terms of respiratory mortality related to air pollution. The participants were randomly provided either placebo or curcumin supplements for 2 weeks and blood samples were collected at the baseline and at the end of the intervention to monitor systemic markers. In our follow up mechanistic study, C57BL/6 mice (n = 40) were randomly allocated into 4 groups: Control group (saline + no acrolein), Curcumin only group (curcumin + no acrolein), Acrolein only group (saline + acrolein), and Acrolein + Curcumin group (curcumin + acrolein). Curcumin was orally administered at 100 mg/kg body weight once a day for 10 days, and then the mice were subjected to nasal instillation of acrolein (5 mg/kg body weight). Twelve hours after single acrolein exposure, all mice were euthanized. RESULTS: Curcumin supplementation, with no noticeable adverse responses, reduced circulating pro-inflammatory cytokines in association with clinical pneumonitis as positive predictive while improving those of anti-inflammatory cytokines. In the pre-clinical study, curcumin reduced pneumonitis manifestations by suppression of intrinsic and extrinsic apoptotic signaling, which is attributed to enhanced redox sensing of Nrf2 and thus sensitized synthesis and restoration of GSH, at least in part, through curcumin-Keap1 conjugation. CONCLUSIONS: Our study collectively suggests that curcumin could provide an effective preventive measure against air pollutant-enhanced pneumonitis and thus COPD.

Curcumin Mediated Gold Nanoparticles and Analysis of its Antioxidant, Anti-inflammatory, Antimicrobial Activity Against Oral Pathogens

ABSTRACT Objective: To green synthesise gold nanoparticles using curcumin and to analyse its antioxidant, anti-inflammatory, and antimicrobial activity among oral pathogens. Material and Methods: Biosynthesised Curcumin Gold nanoparticles (CuAuNP) were evaluated by UV-visible spectrophotometer (UV-Vis), Transmission Electron Microscopy (TEM), and evaluation of antioxidant, anti-inflammatory and antibacterial activity against oral pathogens. Results: Synthesized CuAuNP were characterized using UV-visible spectrophotometry and showed peak absorption at 530nm. CuAuNp showed a 90.3% maximum scavenging ability of DPPH at a concentration of 50 μg/mL. CuAuNP exhibited 79.6 % of the highest anti-inflammatory activity at 50μg/mL than the standard drug diclofenac. TEM image clearly showed uniformly dispersed spherical-shaped gold nanoparticles with a size of about 20 nm. The biosynthesized nanoparticle was tested for its antimicrobial effect, and it showed a potent effect against S. aureus, E. faecalis, and C. albicans at 100µg/ mL. Enterococcus faecalis has a maximum zone of inhibition of 14 mm at 100µg/ mL of CuAuNp. Among gram-positive bacteria, a maximum zone of inhibition of 12 mm at 100µg/ mL was seen in S. aureus compared to S mutans. Candida albicans showed a maximum zone of inhibition of 18 mm at 25 μg/mL of CuAuNp. Conclusion: Curcumin-mediated gold nanoparticles with 20 nm size were effective and had strong antioxidant and anti-inflammatory activity at 50µg/ mL, antimicrobial action inhibiting microbes at 100µg/mL concentration that can be used in treating various Oral mucosal lesions.

Complementary and alternative therapies in skin cancer a literature review of biologically active compounds.

Complementary and alternative medicine or therapies (CAM) are frequently used by skin cancers patients. Patient's self-administration of CAM in melanoma can reach up to 40%-50%. CAMs such as botanical agents, phytochemicals, herbal formulas ("black salve") and cannabinoids, among others, have been described in skin cancer patients. The objective of this review article was to acknowledge the different CAM for skin cancers through the current evidence, focusing on biologically active CAM rather than mind-body approaches. We searched MEDLINE database for articles published through July 2022, regardless of study design. Of all CAMs, phytochemicals have the best in vitro evidence-supporting efficacy against skin cancer including melanoma; however, to date, none have proved efficacy on human patients. Of the phytochemicals, Curcumin is the most widely studied. Several findings support Curcumin efficacy in vitro through various molecular pathways, although most studies are in the preliminary phase. In addition, the use of alternative therapies is not exempt of risks physicians should be aware of their adverse effects, interactions with standard treatments, and possible complications arising from CAM usage. There is emerging evidence for CAM use in skin cancer, but no human clinical trials support the effectiveness of any CAM in the treatment of skin cancer to date. Nevertheless, patients worldwide frequently use CAM, and physicians should educate themselves on currently available CAMs.

Efficacy and safety of dietary polyphenol supplementation in the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Background: Dietary polyphenol treatment of non-alcoholic fatty liver disease (NAFLD) is a novel direction, and the existing clinical studies have little effective evidence for its therapeutic effect, and some studies have inconsistent results. The effectiveness of dietary polyphenols in the treatment of NAFLD is still controversial. The aim of this study was to evaluate the therapeutic efficacy of oral dietary polyphenols in patients with NAFLD. Methods: The literature (both Chinese and English) published before 30 April 2022 in PubMed, Cochrane, Medline, CNKI, and other databases on the treatment of NAFLD with dietary polyphenols was searched. Manual screening, quality assessment, and data extraction of search results were conducted strictly according to the inclusion and exclusion criteria. RevMan 5.3 software was used to perform the meta-analysis. Results: The RCTs included in this study involved dietary supplementation with eight polyphenols (curcumin, resveratrol, naringenin, anthocyanin, hesperidin, catechin, silymarin, and genistein) and 2,173 participants. This systematic review and meta-analysis found that 1) curcumin may decrease body mass index (BMI), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Triglycerides (TG) total cholesterol (TC), and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) compared to placebo; and curcumin does not increase the occurrence of adverse events. 2) Although the meta-analysis results of all randomized controlled trials (RCTs) did not reveal significant positive changes, individual RCTs showed meaningful results. 3) Naringenin significantly decreased the percentage of NAFLD grade, TG, TC, and low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) but had no significant effect on AST and ALT, and it is a safe supplementation. 4) Only one team presents a protocol about anthocyanin (from Cornus mas L. fruit extract) in the treatment of NAFLD. 5) Hesperidin may decrease BMI, AST, ALT, TG, TC, HOMA-IR, and so on. 6) Catechin may decrease BMI, HOMA-IR, and TG level, and it was well tolerated by the patients. 7) Silymarin was effective in improving ALT and AST and reducing hepatic fat accumulation and liver stiffness in NAFLD patients. Conclusion: Based on current evidence, curcumin can reduce BMI, TG, TC, liver enzymes, and insulin resistance; catechin can reduce BMI, insulin resistance, and TG effectively; silymarin can reduce liver enzymes. For resveratrol, naringenin, anthocyanin, hesperidin, and catechin, more RCTs are needed to further evaluate their efficacy and safety.

Curcumin protects islet beta cells from streptozotocin­induced type 2 diabetes mellitus injury via its antioxidative effects.

Streptozotocin (STZ)-induced diabetes rodent models are widely used to study the pathogenesis and metabolic function in diabetes (DM). The aim of this study was to assess the antioxidant effect of curcumin in STZ-induced type 2 diabetes mellitus (T2DM). In this research, rats were randomly divided into 3 groups (8 in each group): a nondiabetic group (Control), a diabetic group (DM), and a curcumin treatment group (DM + Cur 200 mg/kg group). Meanwhile, after intraperitoneal injection (i.p.), associated-oxidative stress parameters were observed, malondialdehyde (MDA) was decreased, and glutathione peroxidase (GPX) and super oxide dismutase (SOD) were restored in pancreatic tissues of curcumin-treated DM rats. In addition, curcumin improved the survival and function of islet cells with decreased cell apoptosis in Langerhans islet and increased insulin secretion in the STZ-induced T2DM rat model. Our findings suggest that curcumin is a potent candidate for the prevention and therapy of DM.

Efficacy and Safety of Curcumin and Curcuma longa Extract in the Treatment of Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trial.

Background: Modern pharmacological research found that the chemical components of Curcuma longa L. are mainly curcumin and turmeric volatile oil. Several recent randomized controlled trials (RCT) have shown that curcumin improves symptoms and inflammation in patients with arthritis. Methods: Pubmed, Cochran Library, CNKI, and other databases were searched to collect the randomized controlled trials (RCTs). Then, the risk of bias of RCTs were assessed and data of RCTs were extracted. Finally, RevMan 5.3 was utilized for meta-analysis. Results: Twenty-nine (29) RCTs involving 2396 participants and 5 types of arthritis were included. The arthritis included Ankylosing Spondylitis (AS), Rheumatoid Arthritis (RA), Osteoarthritis (OA), Juvenile idiopathic arthritis (JIA) and gout/hyperuricemia. Curcumin and Curcuma longa Extract were administered in doses ranging from 120 mg to 1500 mg for a duration of 4-36 weeks. In general, Curcumin and Curcuma longa Extract showed safety in all studies and improved the severity of inflammation and pain levels in these arthritis patients. However, more RCTs are needed in the future to elucidate the effect of Curcumin and Curcuma longa Extract supplementation in patients with arthritis, including RA, OA, AS and JIA. Conclusion: Curcumin and Curcuma longa Extract may improve symptoms and inflammation levels in people with arthritis. However, due to the low quality and small quantity of RCTs, the conclusions need to be interpreted carefully.

Effect of chitosan and curcumin nanoparticles against skeletal muscle fibrosis at early regenerative stage of glycerol-injured rat muscles.

INTRODUCTION: Chitosan and curcumin are natural products that have a wide range of beneficial effects including wound healing. However, their high molecular weight and poor water solubility limit their applications. AIMS: Therefore, the current study aims to evaluate the effects of chitosan (Cs) and curcumin (Cn) nanoparticles (NPs) on fibrosis and regeneration of glycerol-injured muscle. METHODS: Muscle injury was induced by intramuscular injection of glycerol into the tibialis anterior muscle of rats. Cs-NPs and Cn-NPs were administered at different doses intraperitoneally after injury. Injured muscles were collected at day 7 after injury, and muscle fibrosis and regeneration were assessed. RESULTS: The present results revealed that Cs-NPs and Cn-NPs treatment significantly decreased fibrosis index and increased the average myotube diameter with shifting of the distribution of myotube diameters towards larger diameters in a dose-dependent manner. Immunohistochemical analysis revealed that Cs-NPs and Cn-NPs treatment significantly decreased the number of CD-68+ cells and Col-1+ area. Results showed that Cn-NPs had a higher protective effect, in the form of attenuating muscle fibrosis and inflammation, and enhancing muscle regeneration, than that of Cs-NPs. CONCLUSIONS: To our knowledge, this is the first study to document the effects of Cs-NPs in injured muscles. The results of study might be a novel approach to attenuate muscle fibrosis in humans using curcumin and chitosan nanoparticles.

The efficacy of curcumin-piperine co-supplementation on clinical symptoms, duration, severity, and inflammatory factors in COVID-19 outpatients: a randomized double-blind, placebo-controlled trial.

BACKGROUND: COVID-19 pandemic has made the disease a major global problem by creating a significant burden on health, economic, and social status. To date, there are no effective and approved medications for this disease. Curcumin as an anti-inflammatory agent can have a positive effect on the control of COVID-19 complications. This study aimed to assess the efficacy of curcumin-piperine supplementation on clinical symptoms, duration, severity, and inflammatory factors in patients with COVID-19. METHODS: Forty-six outpatients with COVID-19 disease were randomly allocated to receive two capsules of curcumin-piperine; each capsule contained 500 mg curcumin plus 5 mg piperine or placebo for 14 days. RESULTS: Mean changes in complete blood count, liver enzymes, blood glucose levels, lipid parameters, kidney function, and c-reactive protein (CRP) were not significantly different between the two groups. There was a significant improvement in health status, including dry cough, sputum cough, ague, sore throat, weakness, muscular pain, headache, and dyspnea at week 2 in both curcumin-piperine and placebo groups (P value < 0.05); however, the improvement in weakness was more in the curcumin-piperine group than with placebo group (P value 025). CONCLUSION: The present study results showed that curcumin-piperine co-supplementation in outpatients with COVID-19 could significantly reduce weakness. However, in this study, curcumin-piperine co-supplementation could not significantly affect the other indices, including biochemical and clinical indices. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20121216011763N46 . 2020-10-31.

Curcumin improves D-galactose and normal-aging associated memory impairment in mice: In vivo and in silico-based studies.

Aging-induced memory impairment is closely associated with oxidative stress. D-Galactose (D-gal) evokes severe oxidative stress and mimics normal aging in animals. Curcumin, a natural flavonoid, has potent antioxidant and anti-aging properties. There are several proteins like glutathione S-transferase A1 (GSTA1), glutathione S-transferase omega-1 (GSTO1), kelch-like ECH-associated protein 1 (KEAP1), beta-secretase 1 (BACE1), and amine oxidase [flavin-containing] A (MAOA) are commonly involved in oxidative stress and aging. This study aimed to investigate the interaction of curcumin to these proteins and their subsequent effect on aging-associated memory impairment in two robust animal models: D-Gal and normal aged (NA) mice. The aging mice model was developed by administering D-gal intraperitoneally (i.p). Mice (n = 64) were divided into the eight groups (8 mice in each group): Vehicle, Curcumin-Control, D-gal (100mg/kg; i.p), Curcumin + D-gal, Astaxanthin (Ast) + D-gal, Normal Aged (NA), Curcumin (30mg/kg Orally) + NA, Ast (20mg/kg Orally) + NA. Retention and freezing memories were assessed by passive avoidance (PA) and contextual fear conditioning (CFC). Molecular docking was performed to predict curcumin binding with potential molecular targets. Curcumin significantly increased retention time (p < 0.05) and freezing response (p < 0.05) in PA and CFC, respectively. Curcumin profoundly ameliorated the levels of glutathione, superoxide dismutase, catalase, advanced oxidation protein products, nitric oxide, and lipid peroxidation in mice hippocampi. In silico studies revealed favorable binding energies of curcumin with GSTA1, GSTO1, KEAP1, BACE1, and MAOA. Curcumin improves retention and freezing memory in D-gal and nature-induced aging mice. Curcumin ameliorates the levels of oxidative stress biomarkers in mice. Anti-aging effects of curcumin could be attributed to, at least partially, the upregulation of antioxidant enzymes through binding with GSTA1, GSTO1, KEAP1, and inhibition of oxidative damage through binding with BACE1 and MAOA.

Peroxiredoxin 6 mediates the protective function of curcumin pretreatment in acute lung injury induced by serum from patients undergoing one-lung ventilation in vitro.

BACKGROUND: Curcumin has attracted much attention due to its wide range of therapeutic effects. In this study, we used serum collected from patients undergoing one-lung ventilation (OLV) to establish an in vitro acute lung injury (ALI) model to explore the potential protective mechanism of curcumin on ALI. Our study provides a new reference for the prevention and treatment of ALI induced by OLV. METHODS: A549 cells were treated with 20% serum from patients undergoing OLV to establish an in vitro ALI model. Curcumin, at a dose of 40 µg/ml, was administered two hours prior to this model. The levels of inflammation and oxidative stress markers were observed by Western blot, qRT-PCR, ELISA and reactive oxygen species assay. Additionally, the expression of peroxiredoxin 6 (Prdx6) and proteins involved in the NF-κB signaling pathway was evaluated. RESULTS: Twenty percent of serum collected from patients undergoing OLV downregulated the expression of Prdx6, leading to the activation of the NF-κB signaling pathway, which was associated with the subsequent overproduction of inflammatory cytokines and reactive oxygen species. Pretreatment with curcumin restored Prdx6 downregulation and inhibited NF-κB pathway activation by suppressing the nuclear translocation of P65, eventually reducing inflammation and oxidative stress damage in A549 cells. CONCLUSIONS: Prdx6 mediated the protective function of curcumin by inhibiting the activation of the NF-κB pathway in ALI in vitro.

Efficacy of a mixed preparation containing piperine, capsaicin and curcumin in the treatment of alopecia areata.

BACKGROUND: Alopecia areata is a common non-scarring alopecia, mainly manifested as sudden localized patchy alopecia. It is currently believed to be related to autoimmune, genetic, emotional stress, and endocrine factors. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of the mixed preparation of piperine, capsaicin, and curcumin on alopecia areata treatment. METHODS: Sixty patients were enrolled in this study and divided into 2 groups randomly: topical treated with the mixed preparation (case) twice daily and 5%minoxidil (control) once daily for 3 months. The degree of hair loss was assessed by SALT and dermoscopy. RESULTS: On the completion of the study, compared with baseline, statistically significant regrowth occurred in both groups (p < 0.05). The mean SALT scores and hair follicle status under trichoscopy at baseline and at the end of 12 weeks in the mixed preparation group and in the minoxidil group were comparable, respectively. The effective rate of mixed preparation group was 63.33% and minoxidil group was 70%. Adverse symptoms were temporary and no serious adverse event occurred. CONCLUSION: Based on our findings, the mixed preparation of piperine, capsaicin, and curcumin is effective in treating alopecia areata, but it has not been shown to be superior to minoxidil in short-term therapy.

A phase I evaluation of the effect of curcumin on dose-limiting toxicity and pharmacokinetics of irinotecan in participants with solid tumors.

Curcumin inhibits UDP-glucuronyltransferases, a primary metabolic pathway for cancer chemotherapeutic agents like irinotecan. Concurrent administration of both agents may exacerbate irinotecan toxicity. We conducted this phase I study to determine the safety of concurrent curcumin and irinotecan administration. Ten participants with advanced solid tumors received one of four doses (1, 2, 3, and 4 g) of a curcumin phosphatidylcholine complex (PC) orally daily, and 200 mg/m2 of i.v. infusion irinotecan on days 1 and 15 of a 28-day cycle, to determine the maximum tolerated dose (MTD) of PC. Thirteen participants received 4 g of PC (MTD) to assess the effect on the pharmacokinetic (PK) properties of irinotecan and its metabolites, SN-38 and SN-38G. Irinotecan, SN-38, and SN-38G exposure equivalence with and without curcumin was assessed using area under the plasma concentration-time curves from 0 to 6 h (AUC0-6h ). Safety assessments and disease responses were also evaluated. The combination of irinotecan and PC was well-tolerated. Because there was no dose limiting toxicity, the maximum dose administered (4 g) was defined as the recommended phase II dose of PC. PC did not significantly alter the plasma exposure and other PK properties of irinotecan and its metabolites. There was no apparent increase in the incidence of irinotecan-associated toxicities. The objective response rate was 3/19 (22%, 95% confidence interval [CI]: 5-39%), median progression free survival and overall survival (n = 23) were 4 months (95% CI: 2.9-8.9 months) and 8.4 months (95% CI: 3.7 - not evaluable [NE]), respectively. Future studies are required to evaluate the efficacy of this combination.