Inhibition of Apoptosis and Proliferation in T Cells by Immunosuppressive Silymarine

Abstract

Silybum marianum, is known to have anti-inflammatory, hepatoprotective and anticarciogenic effects. The aim of this study was to compare effects of Silymarin, Rapamycin and FK506 on proliferation and apoptosis of human T cells stimulated with Con A. Peripheral blood mononuclear cells (PBMC) were stimulated with concavalin A (Con A) (5 mu g/mL) and then treated with different inhibitors (silymarin, rapamycin and FK506) in various concentrations (5 days). Cells were examined using carboxyfluorescein succinimidyl ester (CFSE) assay for proliferation. Then cell apoptosis was analyzed by FITC annexin V/PI staining and flow cytometry. The effects of drugs on the activation of poly ADP ribose polymerase (PARP) pathway in PBMCs stimulated with Con A and treated with IC50 dose of drugs for 5 days were evaluated using the PathScan cleaved PARP sandwich ELISA kit. The results indicated that silymarin inhibited T cell proliferation. In addition, our results pointed out that 100 mu M and 200 mu M of silymarin significantly have more inhibitory effect on T cells proliferation than FK506 and rapamycin. None of these drugs at IC50 concentration had affected the level of cleaved PARP. Overall, with superior efficacy and lesser toxicity in comparison with other immunosuppressive drugs, silymarin could be a suitable choice of therapy for certain diseases.