A dual effect of ursolic acid to the treatment of multiple sclerosis through both immunomodulation and direct remyelination

Significance Current immunomodulatory therapies for multiple sclerosis (MS) can effectively inhibit autoimmune response, but largely fail to promote myelin repair. This therapeutic deficiency is due mainly to the failure of treatment to promote remyelination in the central nervous system (CNS). Here we show that ursolic acid (UA), a natural triterpenoid, in addition to its well-known antiinflammatory effect, also directly stimulates oligodendrocyte maturation and CNS myelin repair. Mechanisms of UA action involve induction of pro-myelinating neurotrophic factor in astrocytes by PPARγ/CREB signaling and regulation of myelin-related gene expression during oligodendrocyte maturation via PPARγ activation. Our data demonstrate that UA has great potential as an agent for MS, especially at the chronic-progressive stage, because of its capacity in both immunomodulation and neural repair.