Abstract
Various extracts of the Chinese herbal remedy Tripterygium wilfordii Hook. f. (TWHF) have been reported to be therapeutically effective for rheumatoid arthritis (RA) in China, but their action mechanism has not been understood well. In this review, we describe the novel chondroprotective and immunosuppressive effects of triptolide, a diterpenoid triepoxide from TWHF.
Triptolide suppresses the IL-1 α-induced production of proMMPs-1 and -3 along with decrease in their mRNAs in human synovial fibroblasts. In contrast, the IL-1 α-mediated production of tissue inhibitors of metalloproteinases (TIMP) -1 and -2 was further augmented by triptolide in human synovial fibroblasts. Triptolide also inhibits the IL-1 α-induced PGE2 production by selectively suppressing the gene expression and production of cycloxygenase-2. Furthermore, the gene expression of IL-1 α, IL-1 β, TNF-α and IL-6, and the production of IL-1 β and IL-6 are effectively inhibited in the triptolide-treated mouse macrophages.
These data suggest that the therapeutic effects of TWHF in RA are in part due to the novel chondroprotective effects of triptolide via suppression of proMMP production and up-regulation of TIMPs. The interference in the production of proinflammatory cytokines and COX-2 are also very likely to be effective.
