Ursolic acid ameliorates experimental autoimmune encephalomyelitis by regulating Th1 and Th17 cell differentiation (THER3P.877)

Abstract Ursolic acid (UA) is a plant-derived triterpene with potent anti-inflammatory and immunomodulatory activities. In this study we investigated the potential therapeutic effect of UA on the experimental autoimmune encephalomyelitis (EAE), an accepted experimental model of multiple sclerosis. Treatment with UA at initiation or after the disease onset reduced clinical severity and incidence of EAE, which was associated with a decrease in inflammatory infiltrates in spinal cord and in the subsequent demyelination. UA decreased the presence/activation of encephalitogenic Th1 and Th17 cells in both periphery and nervous system, accompanied by down-regulated various inflammatory cytokines and chemokines. The effect of UA was attributable to its selective inhibition of IFN-γ and IL-17 production in CD4+ T cells, mediated via alteration of the STAT pathway and the transcription factors T-bet and RORγt/ROR α. More important, UA has been found novel properties of directly inhibiting Th1 and Th17 cell differentiation in vitro, and was also effective in reducing ongoing paralysis induced by adoptive transfer of either pathogenic Th1 or Th17 cells. These findings indicate that UA exerts potent anti-inflammatory effects through selective modulation of pathogenic Th1 and Th17 cells by targeting critical signaling pathways.