BST204, a Rg3 and Rh2 Enriched Ginseng Extract, Upregulates Myotube Formation and Mitochondrial Function in TNF-α-Induced Atrophic Myotubes

Abstract

The loss of skeletal muscle mass and function is a serious consequence of chronic diseases and aging. BST204 is a purified ginseng (the root of Panax ginseng) extract that has been processed using ginsenoside-$\beta$-glucosidase and acid hydrolysis to enrich ginsenosides Rg3 and Rh2 from the crude ginseng. BST204 has a broad range of health benefits, but its effects and mechanism on muscle atrophy are currently unknown. In this study, we have examined the effects and underlying mechanisms of BST204 on myotube formation and myotube atrophy induced by tumor necrosis factor-$\alpha$ (TNF-$\alpha$). BST204 promotes myogenic differentiation and multinucleated myotube formation through Akt activation. BST204 prevents myotube atrophy induced by TNF-$\alpha$ through the activation of Akt/mTOR signaling and down-regulation of muscle-specific ubiquitin ligases, MuRF1, and Atrogin-1. Furthermore, BST204 treatment in atrophic myotubes suppresses mitochondrial reactive oxygen species (ROS) production and regulates mitochondrial transcription factors such as NRF1 and Tfam, through enhancing the activity and expression of peroxisome proliferator-activated receptor-$\gamma$ coactivator1$\alpha$ (PGC1$\alpha$). Collectively, our findings indicate that BST204 improves myotube formation and PGC1$\alpha$-mediated mitochondrial function, suggesting that BST204 is a potential therapeutic or neutraceutical remedy to intervene muscle weakness and atrophy.

Keywords: Akt/mTOR Pathway; BST204; Ginseng; Mitochondria; Muscle Atrophy; Muscle Regeneration; PGC1$\alpha$.