Low and high doses of ursolic acid ameliorate experimental autoimmune myasthenia gravis through different pathways

Abstract

Myasthenia gravis (MG) is an autoimmune disease characterized by fatigable muscle weakness. Ursolic acid (UA) is a pentacyclic triterpenoid with anti-inflammatory and immunomodulatory properties, especially inhibiting IL-17. We found that UA ameliorated the symptoms of experimental autoimmune myasthenia gravis (EAMG), a rat model of MG. Although both the low and high doses of UA shifted Th17 to Th2 cytokines, other mechanisms were dose dependent. The low dose enhanced Fas-mediated apoptosis, whereas the high dose up-regulated Treg cells and reduced the concentrations of IgG2b antibodies. These findings suggest a new strategy to treat EAMG and even human MG.

Keywords: Apoptosis; Experimental autoimmune myasthenia gravis; Fas; IL-17; Ursolic acid.