Oridonin ameliorates the ferroptosis of chondrocyte to play a chondroprotective role in osteoarthritis.

Chondrocyte dysfunction is a pivotal event in the progression of osteoarthritis (OA). In recent years, ferroptosis has been identified as a key mechanism contributing to chondrocyte functional loss. Given the therapeutic potential of natural compounds derived from Traditional Chinese Medicine for OA, this study aims to investigate whether Oridonin (Ori) exerts a protective effect on osteoarthritic chondrocytes by inhibiting the ferroptosis pathway. Results indicated that Ori inhibited the ferroptosis-related features of chondrocyte via dosage-dependent manner. Mechanistically, acyl-CoA synthetase 4 (ACSL4) was found to be the target of Ori. More findings demonstrated that Ori was capable of suppressing ACSL4, thereby inhibiting ferroptosis in chondrocytes. In conclusion, Ori protected chondrocytes through ACSL4-mediated ferroptosis, which provided a theoretical foundation and a potential therapeutic target for OA.