A study of YangHe Decoction delaying the progression of osteoarthritis by inhibiting chondrocyte ferroptosis through the P53/SLC7A11/GPX4 signaling axis

Abstract Background and Objective: Osteoarthritis (OA) is a chronic degenerative disease characterized by damage and potential loss of articular cartilage for which there is no effective treatment. YangHe Decoction (YHD), a traditional Chinese herbal formula used for the treatment of OA, has been shown to have anti-inflammatory properties, which may be an effective strategy for the treatment of OA. The objective of this study is to investigate the potential mechanism of YHD and its main active ingredient for inhibiting ferroptosis in chondrocytes and for the treatment of OA. Methods: Possible targets and processes of YHD and OA were forecasted using network pharmacology, including relationships between cross-targets of YHD and OA, obtaining key potential targets through PPIs, and revealing possible mechanisms of YHD on OA through GO and KEGG pathway enhancement analyses. Subsequently, in vitro experiments confirmed the expected underlying process. Finally, an in vivo model of DMM-induced C57BL/6 mice model was constructed to validate that YHD ameliorates cartilage degradation and delays the progression of OA. Result: Utilizing a comprehensive approach encompassing network pharmacology, molecular docking, and experimental validation, we have demonstrated that YHD effectively mitigates cartilage degeneration and hinders OA progression in mice in vivo by suppressing IL-1β-mediated ferroptosis within chondrocytes. Conclusion: Our study revealed that YHD was able to slow down osteoarthritis (OA) progression by inhibiting ferroptosis in chondrocytes via the P53/SLC7A11/GPX4 axis.