Oleanolic acid targets the regulation of PI3K/AKT/mTOR pathway and activates autophagy in chondrocytes to improve osteoarthritis in rats

Osteoarthritis (OA) is a degenerative disease that seriously affects an individual's quality of life. Oleanolic acid (OLA) is widely present in food and medicinal plants and has various pharmacological activities. Autophagy is an intracellular protective mechanism, and this study aimed to investigate the potential role of OLA targeting the autophagy pathway in the pathogenesis of OA. A rat OA model was established in vivo by intra-articular injection of Monosodium Iodoacetate (MIA), followed by ELISA, Western blot analysis, and behavioral assays. The results showed that OLA improved OA pain symptoms and inhibit cartilage degeneration. In vitro, OLA inhibited the secretion of inflammatory factors and matrix metalloproteinases in ATDC5 cells after induction with IL-1 beta (10 ng/mL). Meanwhile, Dansylcadaverine (MDC) staining, transmission electron microscopy (TEM), mRFP-GFP-LC3 immunofluorescence, Western blot analysis and RT-qPCR confirmed that OLA activates autophagy by inhibiting the PI3K/AKT/mTOR signaling pathway. In conclusion, OLA shows promise in the treatment of OA.