Immunosuppressive and antiinflammatory effects of triptolide and its prodrug PG-490-88
Triptolide is a diterpenoid triepoxide purified from Tripterygium wilfordii Hook F, an herb found in China. Triptolide inhibits T cell activation mainly through inhibition of interleukin-2 production. In contrast to the target of ciclosporin and FK506, the target of triptolide is at the purine-box/ARRE/NF-AT and NF-κB target sequences after specific binding to DNA. Triptolide also induces apoptosis of T cells by activating the caspase cascade. Moreover, triptolide can suppress the expression of multiple proinflammatory cytokines and mediators, which play important roles in the pathogenesis of autoimmune diseases, transplantation rejection and GVHD. Although data in humans is very limited, triptolide has been successfully used to treat rheumatoid arthritis in humans and prevent bleomycin-induced lung fibrosis in mice. Triptolide significantly prolongs the survival of allogeneic grafts in rats and completely prevents lethal GVHD in mice. Despite its narrow therapeutic window, triptolide is a very potent immunosuppressant and antiinflammatory agent with unique mechanisms of action.
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