Sheng-Yu Jie-Du Tang Lyophilised Extract Reverses Cancer-Induced Myotube Atrophy via PINK1/Parkin-Mediated Mitophagy and Suppression of the NLRP3 Inflammasome

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Abstract

Objective : This study aimed to investigate the impact and mechanism of Shengyu Jiedu Tang(SYJDT) lyophilized powder on a cancer-induced muscular atrophy cell model by modulating the mitochondrial autophagy-NLRP3 inflammatory pathway. Methods : Mouse myoblasts C2C12 were exposed to the supernatant of Lewis lung carcinoma (LLC) to establish a carcinogen-induced muscular atrophy cell model. Various parameters including cell proliferation, migration, myotube atrophy, ROS levels, mitochondrial membrane potential, and expression of proteins in the mitochondrial autophagy-NLRP3 signaling pathway were assessed following treatment with different concentrations of Shengyu Jiedu Tang lyophilized powder. Results : The cancer-induced muscular atrophy cell model was successfully developed, demonstrating myotube atrophy, reduced myotube diameter, elevated TNF-α and IL-6 levels in the culture medium. Treatment with Shengyu Jiedu Tang lyophilized powder significantly suppressed cell proliferation and migration, ameliorated myotube atrophy, decreased ROS levels, enhanced mitochondrial membrane potential, upregulated mitochondrial autophagy-related proteins (LC3, Pink1, Parkin), downregulated P62 protein expression, inhibited NLRP3 inflammasome activation, and reduced inflammatory factor expression. Mitophagy inhibitors partially reversed the effects of the lyophilized powder, suggesting a close association with mitophagy. Conclusion : Shengyu Jiedu Tang lyophilized powder can attenuate cancer-induced muscular atrophy by stimulating mitochondrial autophagy, modulating mitochondrial function, suppressing NLRP3 inflammasome activation, and reducing inflammatory factor expression.

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