Abstract

Setarud is a new herbal medicinal product which is composed of alcoholic extracts of three local plants supplemented with selenium. Preliminary results obtained from in vitro and in vivo investigations have demonstrated immune modulating activity for Setarud. In this study, the in vitro effects of Setarud were investigated on different biological functions of normal human B lymphocytes. Human B lymphocytes were isolated from peripheral blood and stimulated with Toll-like receptor (TLR) 7/8 (R848) and TLR9 (CpG) agonists in presence or absence of different dilutions of Setarud. The effects of Setarud on proliferation, immunoglobulin (Ig) production, IL-10 secretion and expression of the costimulatory molecule CD86 were subsequently studied by 3H-thymidine uptake, ELISA and flow cytometry, respectively. The extract induced a dose-dependent inhibitory effect on all biological functions of TLR stimulated B lymphocytes, particularly at 1/5000 and 1/10000 dilutions. A significant inhibition in proliferation of B lymphocytes stimulated by R848 (p<0.05) and CpG (p<0.01) was observed. IL-10 and Ig production were also inhibited in CpG (p<0.05 and p<0.01, respectively) and R848 (p<0.01 and p<0.05, respectively) stimulated B lymphocytes at 1/5000 dilution of Setarud. The level of CD86 expression in B lymphocytes treated with 1/5000 dilution of Setarud was significantly lower than untreated B lymphocytes (p<0.05).  We observed a significant correlation between all biological functions which were found to be downregulated by Setarud in TLR stimulated B lymphocytes. The dose-dependent inhibitory effect of Setarud on TLR stimulated B lymphocytes implies its potential therapeutic implication in B lymphocyte mediated autoimmune diseases and B-cell malignancies.

Key words: Setarud, herbal extract, immunomodulation, B lymphocyte, immunoglobulin, IL-10, CD86.