Yanghe decoction alleviates osteoarthritis by AMPK-SIRT3 positive feedback loop-mediated Mitochondrial autophagy

Ethnopharmacological relevance: Yanghe Decoction(YHD) is a traditional Chinese medicine compound known for its efficacy in treating osteoarthritis (OA).

Aim of the study: We aimed to explore the underlying mechanisms of YHD in relation to OA.

Materials and methods: UHPLC-MS technology was used to identify the material basis of YHD. In vivo, OA rat model was induced by the modified Hulth method and then treated with YHD at three different doses (0.625, 1.3 and 2.6g/kg/d). In vitro,YHD-Contained serum was prepared and administrated into rat chondrocytes, followed by simulation of Lipopolysaccharide(LPS). The protective mechanism was determined by observation of morphology, Flow cytometry and Protein level detection.

Results: In vivo, YHD reduced chondrocyte apoptosis and joint inflammation while promoting mitophagy. It also elevated the protein levels of p-AMPK, SIRT3, PINK1, Parkin, and LC3II/I. In vitro, YHD-Contained Serum reduced chondrocyte apoptosis, decreased mitochondrial ROS, enhanced mitochondrial membrane potential, and upregulated the protein expressions of p-AMPK, SIRT3, PINK1, Parkin, and LC3II/I.

Conclusion: Through this study, we demonstrated YHD protect chondrocytes against apoptosis, and its underlying mechanisms may involve the regulation of AMPK-SIRT3 positive feedback loop and activation of PINK1/Parkin mediated mitophagy.