Immunosuppressive Effect of Silymarin on MAPK Signaling Pathway: The Impact on T Cell Proliferation and Cytokine Production.

Immunosuppressive Effect of Silymarin on MAPK Signaling Pathway: The Impact on T Cell Proliferation and Cytokine Production.

Basic Clin Pharmacol Toxicol. 2013 May 23;

Authors: Gharagozloo M, Jafari S, Esmaeil N, Bagherpour B, Javid EN, Rezaei A

Abstract

Silymarin, a polyphenolic flavonoid derived from milk thistle (Silybum marianum), is known to have anti-inflammatory, hepatoprotective and anticarcinogenic effects. In this study, the in vitro immunomodulatory effect of silymarin was investigated using human CD4+ T cells. Peripheral blood mononuclear cells (PBMCs) from healthy individuals were activated with anti-CD3 (5μg/ml) plus anti-CD28 (2μg/ml) and treated with 10, 50 and 100μM silymarin. Cells were incubated 72 hr for proliferation assay using MTT and for viability analysis using PI staining and flow cytometry. Naive CD4+ T cell were also isolated from PBMCs, activated with PHA/anti-CD28 and treated with 100μM silymarin for 72 hr. MAPKs activity of cell lysate from activated naive CD4+T cells was assessed using an ELISA-based MAPkinase activity kit and Th1/Th2 related cytokines expression were determined by Multi-Analyte ELISA array Kit. Results indicated a significant inhibition in proliferation of activated PBMC after 48-hr incubation with 100μM silymarin without causing cell death. Moreover, MAPKs activity, (ERK1/2 and P38) and Th1- related cytokines (IL2, TNF-α IFN-γ) were significantly reduced in silymarin-treated cells compared to control after 72 hr. This study shows that silymarin has the ability to inhibit T cell proliferation and pro-inflammatory cytokine secretion in vitro. Furthermore, silymarin is able to inhibit ERK1/2 and P38 pathway activation in T cells stimulated through TCR engagement, a property that is likely associated with its ability to inhibit T cell proliferation and cytokine secretion. Therefore, Silymarin, as an immune-response modifier, might be a valuable drug in therapeutic situations in which immunosuppression is required. This article is protected by copyright. All rights reserved.

PMID: 23701595 [PubMed - as supplied by publisher]