Therapeutic targets of thunder god vine (Tripterygium wilfordii hook) in rheumatoid arthritis (Review).

Celastrol and triptolide, chemical compounds isolated from Tripterygium wilfordii hook (also known as thunder god vine), are effective against rheumatoid arthritis (RA). Celastrol targets numerous signaling pathways involving NF­κB, endoplasmic reticulum Ca2+­ATPase, myeloid differentiation factor 2, toll­like receptor 4, pro­inflammatory chemokines, DNA damage, cell cycle arrest and apoptosis. Triptolide, inhibits NF­κB, the receptor activator of NF­κB (RANK)/RANK ligand/osteoprotegerin signaling pathway, cyclooxygenase­2, matrix metalloproteases and cytokines. The present review examined the chemistry and bioavailability of celastrol and triptolide, and their molecular targets in treating RA. Clinical studies have demonstrated that T. wilfordii has several promising bioactivities, but its multi­target toxicity has restricted its application. Thus, dosage control and structural modification of T. wilfordii are required to reduce the toxicity. In this review, future directions for research into these promising natural products are discussed.