Significant immunomodulatory and hepatoprotective impacts of Silymarin in MS patients: A double-blind placebo-controlled clinicaltrial.

Interferon beta (IFN-ß) has successfully been experimented with to treat multiple sclerosis (MS). However, patients sometimes do not respond effectively to treatment, and |adverse effects, including liver toxicity, accompany this therapy. |Accordingly, we decided to treat MS patients simultaneously with Silymarin (SM) as an immunomodulatory and hepatoprotective agent and IFN-ß in a clinical trial study. Complete blood count (CBC), liver enzyme levels, and the serum concentration of inflammatory and anti-inflammatory cytokines were measured. Also, the frequency of immune cells was determined by flow cytometry. Liver enzyme levels were significantly lower in the intervention group (p < 0.05). The percentage of Th17 cells in the intervention group was significantly reduced compared to the placebo group (P < 0.001). Also, the frequency of Treg cells after treatment with SM plus IFN-ß was significantly increased compared to the placebo group (p < 0.05). Furthermore, the IL-17 and IFNγ cytokine levels were significantly reduced in the intervention group (p < 0.05). Moreover, the levels of anti-inflammatory cytokines IL-10 and TGFß were significantly increased in the intervention group (P < 0.05).Overall, the results provide novel and supplementary information on SM's notable immunoregulatory effects on inflammatory response and liver function in MS patients. Clinical Trial Identifier Number: IRCTID: IRCT20171220037977N1.

Evaluating the Effects of Epigallocatechin-3-Gallate on HIF-1α Protein and RORC Gene Expression in Peripheral Blood Mononuclear Cells in Patients With Multiple Sclerosis.

INTRODUCTION: Multiple Sclerosis (MS) is the chronic inflammation of the Central Nervous System (CNS) and autoimmune disease. MS is most widely considered to be mediated by the activation of myelin-specific T CD4+ cells as well as TH1 and TH17 cells. TH17 cells are involved in the pathogenesis of MS in various manners. HIF-1α and RORC are required for the natural differentiation of TH17; they are essential transcription factors for the evolution of TH17 cells. Numerous studies indicated that Epigallocatechin Gallate (EGCG) presents immunomodulatory and anti-inflammatory effects. This study investigated the effects of EGCG on normoxic HIF-1α and RORC2 expression in PBMCs among MS patients. METHODS: Peripheral Blood Mononuclear Cells (PBMCs) were isolated from the whole blood of new cases of MS. The cells were cultured in the presence of a different concentration of EGCG (25, 50,100µM) for 18 and 48 hours. Next, HIF-1α and RORC2 level expressions were measured by Enzyme-Linked Immunosorbent Assay (ELISA) and Real-Time PCR, respectively. RESULTS: The results showed that EGCG significantly decreased RORC2 gene expression. EGCG did not affect the level of HIF-1α. CONCLUSION: However, EGCG did not influence the level of HIF-1α. Our present data has led us to conclude that EGCG could be considered as an anti-inflammatory agent may serve as an achievable therapeutic agent for MS.

Omega 3 Supplementation Can Regulate Inflammatory States in Gas Station Workers: A Double-Blind Placebo-Controlled Clinical Trial.

Environmental exposure to diesel particulate matter and commercial gasoline in gas station workers might induce oxidative stress and changes in the balance of the immune system. In this study, the immunomodulatory impacts of omega 3 fatty acid (ω3FA) supplement were assessed on inflammatory and anti-inflammatory markers in gas station workers in a double-blind placebo-controlled clinical trial. Fifty-three men working in gas stations were treated with ω3FA (n = 29) or placebo (n = 24) for 60 days. C-reactive protein, interleukin-12 (IL-12), transforming growth factor ß (TGF-ß), interferon γ (IFN-γ), tumor necrosis factor α, IL-10, and IL-17 levels were measured by enzyme-linked immunosorbent assay method before and after the completion of the trial. The concentrations of IFN-γ and IL-17 were significantly decreased in ω3FA group compared with the placebo group (P < 0.001). Moreover, the levels of inhibitory cytokines including TGF-ß and IL-10 significantly were increased in ω3FA group (P < 0.001). Overall, ω3FA nutritional supplementation can be useful in reducing inflammatory immune responses and maintaining immune tolerance in people with high exposure to inflammation-inducing factors. [Figure: see text].

Silymarin Restores Regulatory T Cells (Tregs) Function in Multiple Sclerosis (MS) Patients In Vitro.

Dysregulation of the immune system and impairment in the function and number of patient-derived regulatory T cells (Treg) have an important role in multiple sclerosis (MS) pathogenesis. MS patients still receive different medications to overcome the relapses and to slow the disease progression. However, the benefits of these therapies are limited and are accompanied by different side effects. The immunoregulatory effects of Silymarin as a plant-derived flavonoid have shown in studies. In the present study, regulatory T cells (Tregs) were isolated from MS patients who diagnosed as new cases and IFN-ß-treated RRMS patients. Isolated Treg cells were cultured in the presence of different concentrations of Silymarin (50, 100, 150 µM) for 48, 72, and 120 h. Proliferation and activation of Treg cells were assessed by flow cytometry. Also, FOXP3, JAK3, and STAT5 gene expression, IL-10, and TGF-ß production by Tregs were evaluated by real-time PCR and ELISA respectively. The results showed that Silymarin promoted Treg proliferation at 100 µM concentration after 72 h. Additionally, IL-10, TGF-ß levels, and FOXP3, JAK3, and STAT5 gene expression enhanced by Silymarin dose and time dependently. Our preliminary results suggest that the induction and activation of Tregs could be an underlying mechanism of the ancient used herbal medicine Silymarin, providing effective means against autoimmune and inflammatory diseases.

Immunoregulatory Effects of Silymarin on Proliferation and Activation of Th1 Cells Isolated from Newly Diagnosed and IFN-ß1b-Treated MS Patients.

Multiple sclerosis (MS) is a central nervous system autoimmune disease characterized by demyelination. Autoreactive T cells mainly interferon gamma (IFN-γ) producing T helper cells (Th1) have an important role in MS pathogenesis. Silymarin is a unique blend produced from milk thistle (Silybum marianum) plant which its imunomodulatory role has been indicated in studies. In the present study, the effects of silymarin on isolated Th1 cells were investigated in newly diagnosed MS patients and those who received betaferon. PBMCs were separated from newly diagnosed and IFN-ß-treated MS patients. The Th1 cell isolation from PBMCs was performed using a human Th1 cell isolation kit. Th1 cells were cultured in the presence of silymarin (50, 100, and 150 µM for 48, 72, and 120 h). Th1 cell proliferation and CD69 expression were assessed by flow cytometry. Also, IFN-γ production and T-bet gene expression were measured by ELISA and real-time PCR respectively. In vitro cultured Th1 cells showed that silymarin suppresses Th1 cell proliferation dose and time dependently in newly diagnosed and IFN-ß-treated MS patients in comparison to DMSO control. Also, CD69 expression as an early activation marker was changed after Th1 cell treatment with different doses of silymarin at different times. T-bet gene expression was significantly decreased in Th1 cells isolated from newly diagnosed and IFN-ß-treated RRMS patients after treatment with silymarin compared to DMSO control. Additionally, IFN-γ production by Th1 cells was decreased after treatment silymarin in newly diagnosed patients; however, in IFN-ß treated after 48-h treatment with silymarin, IFN-γ concentration was decreased at concentrations of 100 and 150 µM, and after 120 h, a significant increase was observed in the IFN-γ level at a concentration of 100 µM in comparison with DMSO. Our findings here clearly show that silymarin is an effective regulator for Th1 response in vitro condition. It not only suppresses Th1 proliferating activity but also inhibits T-bet gene expression and IFN-γ production by these cells.