Ginsenoside Rg3 protects glucocorticoid-induced muscle atrophy in vitro through improving mitochondrial biogenesis and myotube growth

Ginsenoside Rg3 (Rg3), amplified by iterative heating processing with fresh ginseng, has a broad range of pharmacological activities and improves mitochondrial biogenesis in skeletal muscle. However, thus far no study has examined how Rg3 affects myotube growth or muscle atrophy, to the best of the authors' knowledge. The present study was conducted to examine the myogenic effect of Rg3 on dexamethasone (DEX)-induced myotube atrophy and the underlying molecular mechanisms. Rg3 activated Akt/mammalian target of rapamycin signaling to prevent DEX-induced myotube atrophy thereby stimulating the expression of muscle-specific genes, including myosin heavy chain and myogenin, and suppressing muscle-specific ubiquitin ligases as demonstrated by immunoblotting and immunostaining assays. Furthermore, Rg3 efficiently prevented DEX-triggered mitochondrial dysfunction of myotubes through peroxisome proliferator-activated receptor-gamma coactivator1 alpha activities and its mitochondrial biogenetic transcription factors, nuclear respiratory factor-1 and mitochondrial transcription factor A. These were confirmed by immunoblotting, luciferase assays, RT-qPCR and mitochondrial analysis measuring the levels of ROS, ATP and membrane potential. By providing a mechanistic insight into the effect of Rg3 on myotube atrophy, the present study suggested that Rg3 has potential as a therapeutic or nutraceutical remedy to intervene in muscle aging or diseases including cancer cachexia.