Ginsenoside Rc prevents dexamethasone-induced muscle atrophy and enhances muscle strength and motor function

Background: A decline in muscle mass and function can impact the health, disease vulnerability, and mortality of older adults. Prolonged use of high doses of glucocorticoids, such as dexamethasone (DEX), can cause muscle wasting and reduced strength. Ginsenoside Rc (gRc) has been shown to protect muscles by activating the PGC-1 alpha pathway and improving mitochondrial function. The effects of gRc on muscle atrophy and function in mice are not fully understood. Methods and results: The study discovered that gRc prevented the DEX-induced decrease in viability of C2C12 myoblasts and myotubes. Furthermore, gRc inhibited myotube degradation and the upregulation of muscle degradation proteins induced by DEX. Transcriptome analysis of myotubes showed that gRc enhances muscle generation processes while suppressing the TGF-beta pathway and oxidative stress response. In mice, gRc effectively reversed the reductions in body weight, muscle mass, and muscle fibers caused by DEX. Furthermore, gRc significantly enhanced muscle strength and exercise capacity. Docking and transcriptome analyses indicated that gRc may act as a competitive inhibitor of DEX at the glucocorticoid receptor, potentially preventing muscle loss. Conclusion: The study suggests that gRc can prevent DEX-induced muscle wasting and weakness. Consequently, it may be a viable treatment option for sarcopenia and muscle-related disorders in various medical conditions.