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

BackgroundMultiple 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.MethodsThe 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-β), 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.FindingsEllagic 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-β 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).ConclusionEllagic 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

Cardiac tissue oxidative stress and inflammation after vitamin D administrations in high fat- diet induced obese rats

Abstract Background Obesity is associated with numerous metabolic and inflammatory disorders. The current study was aimed to evaluate the effects of vitamin D administration on the markers of oxidative stress and inflammation in the cardiac tissue of high-fat diet induced obese rats. Methods In the beginning of the study, 40 male Wistar rats were divided into two groups: normal diet (ND) and high fat diet (HFD) for 16 weeks; then each group subdivided into two groups including: ND, ND + vitamin D, HFD and HFD + vitamin D. Vitamin D supplementation was done for 5 weeks at 500 IU/kg dosage. Tumor necrosis factor (TNF)-α concentration and markers of oxidative stress including glutathione peroxidase (GPx), superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT) concentrations in the cardiac tissue and serum concentrations of lipids in rats were determined using ELISA kits and spectrophotometry methods respectively. Results According to our results, GPx activity in ND and ND + vitamin D group was significantly higher compared with HFD group. Similarly, SOD activity was also significantly increased in ND + vitamin D group compared with ND and HFD groups. Moreover, vitamin D administration, significantly reduced catalase activity in ND + vitamin D and HFD + vitamin D groups (P < 0.05). TNF-α concentration in heart tissue in ND + vitamin D group significantly reduced compared with ND group. Cardiac tissue MDA concentration in baseline or after vitamin D administration did not changed significantly. Conclusion Vitamin D improved cardiac oxidative stress and inflammatory markers in HFD induced obese rats. Further studies in human models are needed to further confirm the use of this nutrient in daily clinical practice

Mediterranean dietary pattern and VEGF +405 G/C gene polymorphisms in patients with metabolic syndrome: An aspect of gene-nutrient interaction.

AIMS:To evaluate the relationship between Mediterranean dietary pattern, anthropometric and metabolic biomarkers and vascular endothelial growth factor (VEGF) +405 G/C gene polymorphism in patient with metabolic syndrome (Mets). MATERIALS AND METHODS:In this study 150 patients with Mets and 50 healthy subjects were enrolled. Dietary intakes were evaluated with a semi-quantitative food-frequency questionnaire (FFQ) and Mediterranean dietary quality index (Med-DQI) was assessed. Anthropometric assessments and blood pressure measurement were performed. Biochemical assays including fasting serum glucose (FSG), matrix metalloproteinase-3 (MMP-3), liver enzymes and lipid profiles were also assessed. Polymorphism of +405 G/C VEGF gene was determined utilizing polymerase chain reaction-restriction fragments length polymorphism (PCR-RFLP) method. RESULTS:Serum high density lipoprotein-cholesterol (HDL-C) was significantly lower and low density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC) concentrations and FSG were significantly higher in metabolic syndrome patients compared with control group (P < 0.05). Metabolic syndrome group with high consumption of "cholesterol" had significantly upper serum TG; also high consumption of "fish" and "vegetables-fruits" was associated with a significantly lower serum LDL concentrations. In metabolic syndrome patients with CC genotype, mean score of "saturated fatty acid" subgroup was significantly higher compared with other genotypes; whereas, in healthy individuals, mean score of "fruit-vegetable" subgroup in individuals of CC and GG genotype was significantly higher (P<0.05). CONCLUSION:Our findings indicated a significant relationship between Mediterranean dietary quality index and both anthropometric and metabolic risk factors. We also indicated a higher "saturated fatty acid" intake in CC genotype among metabolic syndrome patients

The effects of vitamin D administration on brain inflammatory markers in high fat diet induced obese rats

Abstract Background Obesity induced brain inflammation is associated with cognitive disorders. We aimed to investigate the influence of vitamin D on hypothalamus and hippocampus inflammatory response in high-fat diet induced obese rats. Methods In the beginning of the study, 40 rats were divided into two groups: control diet and high fat diet (HFD) for 16 weeks; then each group subdivided into two groups including: N, ND + vitamin D, HFD and HFD + vitamin D. Vitamin D supplementation was done for 5 weeks at 500 IU/kg dosage. IL-6, IL-1β, NF-Kβ and acetylcholine (ACH) and brain derived neurotropic factor (BDNF) concentrations in hippocampus and hypothalamus homogenate samples were measured by commercial ELISA kits. Results Vitamin D administration, reduced food intake and weight gain in studied groups (P < 0.001). Vitamin D reduced hippocampus acetylcholine concentrations in ND + vitamin D group (P < 0.001). High fat diet increased hippocampus IL-6 concentrations significantly (P < 0.05) compared with normal diet receiving groups. Vitamin D could not have significant effects on IL-6 concentrations. Vitamin D administrations reduced IL-1β, NF-Kβ and acetylcholine concentration and BDNF concentrations in ND + vitamin D compared with ND group. These reductions were not significant in HFD + vitamin D versus HFD group. Conclusion According to our results, vitamin D reduced food intake and weight gain and modulated the HFD induced inflammatory response in hippocampus and hypothalamus of high fat diet induced obesity. Therefore, this neurosteroid, can be suggested as a supplemental therapeutic tool in prevention of obesity related cognitive and neurodegenerative problems

PCR–RFLP analysis for +405 VEGF gene polymorphism.

<p>PCR–RFLP analysis for +405 VEGF gene polymorphism.</p

Comparison of biochemical parameters according to components of Med-DQI in patients with metabolic syndrome.

<p>Comparison of biochemical parameters according to components of Med-DQI in patients with metabolic syndrome.</p

General demographic, anthropometric and biochemical parameters in patients with metabolic syndrome compared to healthy controls.

<p>General demographic, anthropometric and biochemical parameters in patients with metabolic syndrome compared to healthy controls.</p

Comparison of anthropometric parameters according to components of Med-DQI in healthy control group.

<p>Comparison of anthropometric parameters according to components of Med-DQI in healthy control group.</p

Comparison of components of Med-DQI according to +405 G/C of VEGFgene polymorphism between study groups.

<p>Comparison of components of Med-DQI according to +405 G/C of VEGFgene polymorphism between study groups.</p