Brevilin A attenuates cartilage destruction in osteoarthritis mouse model by inhibiting inflammation and ferroptosis via SIRT1/Nrf2/GPX4 signaling pathway

Abstract

Osteoarthritis (OA) is a serious orthopedic disease that affects people's quality of life. Although there are many treatment methods, the treatment effect is still not good. Brevilin A is a bioactive compound isolated from the medicinal herbCentipeda minima. The potential efficacy of brevilin A on OA was explored in this study. Mouse chondrocytes were isolated and stimulated by IL-1β and mouse OA model was induced by destabilization of the medial meniscus (DMM). The results demonstrated that brevilin A markedly inhibited IL-1β-induced MMP1 and MMP3 production. IL-1β-induced PGE₂, NO, MDA, and iron production were alleviated by brevilin A. The production of GSH and the expression of SIRT1, Nrf2, HO-1, GPX4, and Ferritin were increased by brevilin A. Furthermore, the inhibition of brevilin A on IL-1β-induced inflammation and ferroptosis were prevented by SIRT1 inhibitor. In vivo, the results showed brevilin A markedly attenuated OA progression in DMM-induced mouse OA model. Also, brevilin A could alleviate MMP1, MMP3, iNOS, and COX2 expression in OA mice. In conclusion, brevilin A protected mice against OA via suppressing inflammatory response and ferroptosis by regulating SIRT1/Nrf2/GPX4 signaling.

Keywords: Brevilin A; Ferroptosis; MMP1; Osteoarthritis; SIRT1.