Resveratrol alleviates osteoarthritis progression by inhibiting NLRP3 inflammasome response via the AMPK/PPARγ signaling pathway

Abstract

Osteoarthritis (OA) is a chronic, degenerative disease affecting joint tissue. Resveratrol (RES), a natural polyphenolic compound, has anti-inflammatory, antioxidant and anti-apoptotic effects in chondrocytes and macrophages, suggesting therapeutic potential for OA. The present study investigated the molecular mechanisms of RES in OA treatment through network pharmacology analysis and in vitro and in vivo experiments. Network pharmacology was performed to identify potential therapeutic targets and pathways. An OA cell model was established by treating SW1353 cells with IL-1β, followed by RES intervention without or with AMPK inhibitor to evaluate the effects on the AMPK/PPARγ signaling pathway, NLRP3 inflammasome response, and extracellular matrix (ECM) metabolism. For in vivo assays, OA mice were established through the destabilization of the medial meniscus (DMM) surgery, and administered RES through oral gavage. Histopathological changes, serum inflammatory factors and the expression of target proteins in articular cartilage were analyzed. Network pharmacology identified the AMPK/PPARγ pathway as a key mechanism underlying the therapeutic effects of RES in OA. In vitro, RES activated the AMPK/PPARγ pathway and inhibited the NLRP3 inflammasome response, thereby preserving ECM homeostasis in SW1353 cells. In vivo, RES alleviated OA progression by suppressing cartilage degeneration and synovitis, and regulating serum inflammatory levels. The target protein changes were consistent with the in vitro findings. The present study demonstrates that RES effectively regulates the NLRP3 inflammasome response by activating the AMPK/PPARγ signaling pathway, providing a valuable experimental foundation and potential clinical utility for RES as a complementary and alternative therapy for OA.