Angelica Sinensis polysaccharide attenuates chondrocyte ferroptosis and alleviates cartilage degeneration in OA

Abstract Osteoarthritis (OA) is one of the common degenerative diseases. Its main pathogenesis is the progressive destruction of articular cartilage, synovitis, subchondral bone, and periarticular muscle changes. Accumulating evidence demonstrates that ferroptosis may be important in the progression of OA. Angelica Sinensis polysaccharide (ASP), a traditional Chinese medicine, possesses antioxidative, anti-inflammatory and anti-apoptotic properties in chondrocytes. In this study, we observed that ferroptosis participates in OA’s progression. Importantly, GPX4, FTH1, and GSH expressions were higher while MDA level was down-regulated in the control group than in the OA group. Chondrocyte ferroptosis induced by erastin or IL-1β was rescued to varying degrees by ASP, Fer-1, or DFO in vitro. The anti-ferroptotic effect of ASP was related to Nrf2 nuclear transfer. In the rat joints, both DFO and ASP alleviated the cartilage damage induced by DMM or erastin. In summary, Chondrocyte ferroptosis plays a key role in OA progression, and ASP can partially rescue chondrocyte ferroptosis through the Nrf2-SLC7A11-GPX4 axis, supporting the view that ASP is an excellent inhibitor of ferroptosis, its inhibition of ferroptosis provides a potential therapeutic target for the treatment of OA.