Astragalus polysaccharides ameliorate osteoarthritis via inhibiting apoptosis by regulating ROS-mediated ASK1/p38 MAPK signaling pathway targeting on TXN

This research aims to explore the potential of astragalus polysaccharides (APS) in treating osteoarthritis. The primary component of APS extracted in this study was glucose, and noticeably it had a relatively high content of glucuronic acids. In vitro, APS reduced ROS levels, protected chondrocytes from apoptosis, and promoted collagen II expression by regulating ASK1 (apoptosis-signal-regulating kinase1)/p38 cell apoptosis pathway. Further co-immunoprecipitation and immunofluorescence localization experiments demonstrated that the thioredoxin (TXN) antioxidant system was responsible for its bioactivity. Moreover, TXN silencing remarkably blocked the protective effects of APS, indicating that APS inhibited chondrocyte apoptosis by targeting TXN. In vivo, APS effectively mitigated cartilage loss and chondrocyte apoptosis and decreased expressions of p-ASK1 and p-p38. Collectively, this research first demonstrated that APS could ameliorate osteoarthritis by ASK1/p38 signaling pathway through regulating thioredoxin. In conclusion, APS holds promise as a nutraceutical supplement for osteoarthritis in future drug development.