Betulinic acid inhibits cell proliferation, migration, and inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes.

Abstract

Betulinic acid (BA), a pentacyclic triterpene derived from the bark of the white birch tree, has been reported to have a variety of pharmacological effects, including antioxidant, anti-inflammatory, antitumor, immunomodulatory, and antiarthritis properties. However, the role of BA in rheumatoid arthritis (RA) remains unclear. Thus, the objective of this study was to examine the effects of BA on RA fibroblast-like synoviocytes (RA-FLS) proliferation, migration, and inflammatory response, and further explore the potential underlying mechanisms. Our results showed that BA inhibited the proliferation, migration, and invasion of RA-FLSs. BA also attenuated tumor necrosis factor-α (TNF-α), enhanced matrix metalloproteinases (MMPs) expression, and inflammatory cytokines production in RA-FLS. Furthermore, BA prevented the activation of Akt/NF-κB pathway in RA-FLS exposed to TNF-α. In conclusion, these findings indicated that BA inhibits cell proliferation, migration, and inflammatory response in RA-FLS; and the Akt/NF-κB signaling pathway was involved in the protective effect of BA on RA-FLS. Thus, BA might be a potential therapeutic agent for the treatment of RA.