Ellagic acid effects on disease severity, levels of cytokines and T-bet, RORγt, and GATA3 genes expression in multiple sclerosis patients: a multicentral-triple blind randomized clinical trial.

Background: Multiple sclerosis (MS) is a chronic autoimmune disease. Ellagic acid is a natural polyphenol and affects the fate of neurons through its anti-inflammatory and antioxidant properties. The present study aimed to investigate ellagic acid effects on disease severity, the expression of involved genes in the pathogenesis of MS, and the levels of related cytokines. Methods: The present study was a triple-blind clinical trial. Eligible patients were randomly assigned to two groups: Ellagic acid (25 subjects) for 12 weeks, receiving 180 mg of Ellagic acid (Axenic, Australia) and the control group (25 subjects) receiving a placebo, before the main meals. Before and after the study, the data including general information, foods intake, physical activity, anthropometric data, expanded disability status scale (EDSS), general health questionnaire (GHQ) and pain rating index (PRI), fatigue severity scale (FSS) were assessed, as well as serum levels of interferon-gamma (IFNγ), interleukin-17 (IL-17), interleukin-4 (IL-4) and transforming growth factor-beta (TGF-ß), nitric-oxide (NO) using enzyme-linked immunoassay (ELISA) method and expression of T-box transcription factor (Tbet), GATA Binding Protein 3 (GATA3), retinoic acid-related orphan receptor-γt (RORγt) and Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes were determined using Real-Time Quantitative Reverse Transcription PCR (RT-qPCR) method. Findings: Ellagic acid supplementation led to a reduction in IFNγ, IL-17, NO and increased IL-4 in the ellagic acid group, however in the placebo group no such changes were observed (-24.52 ± 3.79 vs. -0.05 ± 0.02, p < 0.01; -5.37 ± 0.92 vs. 2.03 ± 1.03, p < 0.01; -18.03 ± 1.02 vs. -0.06 ± 0.05, p < 0.01, 14.69 ± 0.47 vs. -0.09 ± 0.14, p < 0.01, respectively). Ellagic acid supplementation had no effect on TGF-ß in any of the study groups (p > 0.05). Also, the Tbet and RORγt genes expression decreased, and the GATA3 gene expression in the group receiving ellagic acid compared to control group significantly increased (0.52 ± 0.29 vs. 1.51 ± 0.18, p < 0.01, 0.49 ± 0.18 vs. 1.38 ± 0.14, p < 0.01, 1.71 ± 0.39 vs. 0.27 ± 0.10, p < 0.01). Also, ellagic acid supplementation led to significant decrease in EDSS, FSS and GHQ scores (p < 0.05), and no significant changes observed in PRI score (p > 0.05). Conclusion: Ellagic acid supplementation can improve the health status of MS patients by reduction of the inflammatory cytokines and Tbet and RORγt gene expression, and increment of anti-inflammatory cytokines and GATA3 gene expression.Clinical trial registration: (https://en.irct.ir/trial/53020), IRCT20120415009472N22.

The effects of aqueous and ethanolic extracts of Rheum ribes on insulin-resistance and apolipoproteins in patients with type 2 diabetes mellitus: a randomized controlled trial.

BACKGROUND AND AIM: Previous studies have shown that Rheum ribes (R. ribes) could be effective in controlling the blood glucose levels. This study was conducted to determine the effects of R. ribes supplementation on glycemic indices and apolipoproteins in patients with type 2 diabetes mellitus (T2DM). METHODS: In the present randomized double-blind controlled trial, 60 type 2 diabetic patients aged 30-60 years with a body mass index (BMI) of 20-30 kg/m2 and hemoglobin A1c (HbA1c) of 6-8% were enrolled. Patients were randomly assigned to receive 450 mg of aqueous R. ribes extract (AG), 450 mg of ethanolic R. ribes extract (EG), or placebo (PG) three times daily for 6 weeks. At the baseline and at the end of the study, blood glucose levels, homeostatic model assessment of insulin resistance (HOMA-IR) and the homeostatic model assessment of ß-cell dysfunction (HOMA-B), as well as apolipoprotein A-I (ApoA1) and apolipoprotein B (ApoB) were measured. RESULTS: There was a significant decrease in the serum levels of insulin in AG and EG groups (P = 0.003 and P = 0.001, respectively), HOMA-IR (P = 0.01 and P = 0.001, respectively), HOMA-B (P = 0.002 and P = 0.001, respectively), ApoB (P = 0.006 and P = 0.03, respectively), ApoB/ApoA1 ratio (P = 0.016 and P = 0.04, respectively). However, a significant increase in ApoA1 (P = 0.08 and P = 0.05, respectively) with no significant changes in blood glucose, at the end of study compared to beginning values, were observed. None of the variables showed a significant change in PG. At the end of the study; while there were significant differences in insulin (P = 0.04), HOMA-IR (P = 0.03), HOMA-B (P = 0.01), ApoB (P = 0.02), and ApoB/ApoA1 ratio (P = 0.03) among the groups but ApoA1 had no significant change. CONCLUSION: Consumption of R. ribes intake could have beneficial effects on insulin resistance and apolipoproteins in type 2 diabetic patients. (Registered at en.irct.ir, identification number: IRCT201410142709N31).

Diabetes, Age, and Duration of Supplementation Subgroup Analysis for the Effect of Coenzyme Q10 on Oxidative Stress: A Systematic Review and Meta-Analysis.

BACKGROUND: Coenzyme Q10 (CoQ10) has been known as ubiquinone or ubidecarenone, which is a kind of lipid-soluble and vitamin-like antioxidant. It has a potent antioxidant effect against oxidation status via various mechanisms, including its ability to regenerate other antioxidants, such as vitamin E and vitamin C, and to increase antioxidant enzymes. Moreover, CoQ10 can quench free radicals and prevent lipid peroxidation. The aim of this systematic review and meta-analysis was to evaluate the effect of CoQ10 on oxidative stress variables. METHODS: A comprehensive electronic database search in Scopus, Web of Science, Embase, Cochrane Library, and Medline was performed to identify eligible randomized clinical trials. A meta-analysis of included studies was performed on selected variables using a random-effects model. Quality assessment was conducted by means of the Cochrane risk of bias assessment tool. RESULTS: To evaluate the effect of CoQ10 supplementation, 17 trials and 972 participants were included for the meta-analysis. The pooled analysis of primary studies showed that CoQ10 increased serum total antioxidant capacity (standardized mean difference [SMD] 0.62 mmol/L, 95% CI 0.18-1.05, I2 = 76.1%, p ˂ 0.001) and superoxide dismutase (SMD 0.40 U/mg, 95% CI 0.12-0.67, I2 = 9.6%, p ˂ 0.345) levels and decreased malondialdehyde (SMD -1.02 mmol/L, 95% CI -1.60 to -0.44, I2 = 88.2%, p ˂ 0.001) level significantly compared to the placebo group. Although the effect of CoQ10 on nitric oxide (SMD 1.01 µmol/L, 95% CI -1.53 to 3.54, p ˂ 0.001, I2 = 97.8%) and glutathione peroxidase (SMD -0.01 mmol/L, 95% CI -0.86 to 0.84, p ˂ 0.001, I2 = 88.6%) was not significant, CoQ10 can be mentioned as an improvement in antioxidant defense status against reactive oxygen species. CONCLUSION: These supplements have positive effects on antioxidant defense against oxidizing agents and elevate antioxidant enzyme levels in the body. However, due to limited research the results should be taken with caution.

The effect of ginger supplementation on some immunity and inflammation intermediate genes expression in patients with active Rheumatoid Arthritis.

OBJECTIVE: Rheumatoid Arthritis (RA) is an autoimmune disease. The aim of this study was to investigate the effect of ginger supplementation on the expression of some immunity and inflammation intermediate genes in patients who suffer from RA. METHODS: In this randomized double-blind placebo-controlled clinical trial, seventy active RA patients were allocated randomly into two groups who either received 1500 mg ginger powder or placebo daily for 12 weeks. Disease activity score and gene expression of NF-κB, PPAR-γ, FoxP3, T-bet, GATA-3, and RORγt as immunity and inflammation intermediate factors were measured using quantitative real-time PCR before and after the intervention. RESULTS: After the intervention, FoxP3 genes expression increased significantly within ginger group and between the two groups (P-value = 0.02). Besides, T-bet and RORγt genes expression decreased significantly between the two groups (P-value < 0.05). In ginger group, PPAR-γ genes expression increased significantly (P-value = 0.047) but the difference between the two groups wasn't statistically significant (P-value = 0.12). The reduction in disease activity score was statistically significant within ginger group and between the two groups after the intervention. CONCLUSION: It seems that ginger can improve RA by decreasing disease manifestations via increasing FoxP3 genes expression and by decreasing RORγt and T-bet genes expression.