Alisol A 24-acetate ameliorates osteoarthritis progression by inhibiting reactive oxygen species and inflammatory response through the AMPK/mTOR pathway

IntroductionOsteoarthritis 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-1 beta-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-1 beta-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-alpha, 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.