AbstractIntroductionOsteoarthritis is a degenerative knee joint disease featured with articular cartilage degeneration and inflammation. Alisol A 24‐acetate (ALA‐24A) is an active triterpene that has antioxidant and anti‐inflammatory pharmacological properties. However, its effect and molecular mechanism on osteoarthritis progression have not been reported.MethodsIL‐1β‐induced chondrocyte injury model and monosodium iodoacetate (MIA)‐induced rat osteoarthritis model were used. The protective effects of ALA‐24A on osteoarthritis were evaluated by determining cell viability, extracellular matrix (ECM) degradation, inflammatory response and oxidative stress using CCK‐8 assay, Western blot, ELISA, and DCFH‐DA fluorescent probe. The severity and matrix degradation of articular cartilage were assessed by histopathological and immunohistochemical examination.ResultsWe found that ALA‐24A attenuated IL‐1β‐induced cell viability inhibition Moreover, ALA‐24A suppressed expression levels of ECM degradation‐related genes ADAMTS5 and MMP13, and promoted expression levels of ECM synthesis‐related genes Aggrecan and Collagen II. In addition, ALA‐24A treatment decreased reactive oxygen species (ROS) production and increased antioxidant enzymes (SOD, CAT, and GSH‐px) activities, while increased MDA levels. The inflammatory levels of NO, PGE2, TNF‐α, and IL‐6 were also reduced following treatment with ALA‐24A. Our data also revealed that ALA‐24A treatment triggered p‐AMPK upregulation and p‐mTOR downregulation. In rat osteoarthritis model, ALA‐24A treatment significantly alleviated the severity and matrix degradation of articular cartilage comparted with model group.ConclusionsOur findings suggested a protective role of ALA‐24A against osteoarthritis by inhibiting ROS and inflammatory response. Furthermore, ALA‐24A might be a promising therapeutic option for osteoarthritis treatment.