PG201 protects mice from experimental autoimmune encephalomyelitis via suppression of effector T cell activation.

BACKGROUND: PG201 is a botanical formulation, approved as an ethical drug (ETC) phytomedicine for treatment of patients with osteoarthritis in Korea, following satisfactory phase II and phase III studies. This phytomedicine was previously been shown to possess significant anti-inflammatory activities, presumably via the control of Th1 and Th17 cells in animal models and in vitro cell culture systems.

PURPOSE: In this study, the possibility of using PG201 to treat multiple sclerosis was explored.

METHODS: In vitro, the effect of PG201 on the differentiation of CD4+ T cells was investigated. To test the effects of PG201 in vivo, a mouse experimental autoimmune encephalomyelitis (EAE) model was used.

RESULTS: It was found that PG201 treatment decreased the frequency of both CD4+ T-bet+ and CD4+ RORγt+ T cells. In addition, the production of interferon- gamma (IFN-γ) and interleukin-17 (IL-17) from respective Th cells was highly reduced. The data from western blots showed that the amount of phosphorylated c-Jun, but not that of p65, was decreased by PG201. Consistently, the level of luciferase activity was downregulated by PG201 in activator protein 1 (AP-1) reporter plasmid assays. In mice pretreated with PG201, the day of onset was delayed and clinical symptoms of EAE were significantly improved in a dose-dependent manner. Consistent with these results, the number of infiltrated cells and the expression level of pro-inflammatory molecules were decreased.

CONCLUSION: These findings indicate that PG201 may exert strong immunomodulatory effects in the EAE model via suppression of T cell activation, and that PG201 is a therapeutic reagent for the treatment of multiple sclerosis.