Ginsenoside Rg5 promotes muscle regeneration via p38MAPK and Akt/mTOR signaling.

Background: Skeletal muscles play a key role in physical activity and energy metabolism. The loss of skeletal muscle mass can cause problems related to metabolism and physical activity. Studies are being conducted to prevent such diseases by increasing the mass and regeneration capacity of muscles. Ginsenoside Rg5 has been reported to exhibit a broad range of pharmacological activities. However, studies on the effects of Rg5 on muscle differentiation and growth are scarce. Methods: To investigate the effects of Rg5 on myogenesis, C2C12 myoblasts were induced to differentiate with Rg5, followed by immunoblotting, immunostaining, and qRT-PCR for myogenic markers and promyogenic signaling (p38MAPK). Immunoprecipitation confirmed that Rg5 increased the interaction between MyoD and E2A via p38MAPK. To investigate the effects of Rg5 on prevention of muscle mass loss, C2C12 myotubes were treated with dexamethasone to induce muscle atrophy. Immunoblotting, immunostaining, and qRT-PCR were performed for myogenic markers, Akt/mTOR signaling for protein synthesis, and atrophy-related genes (Atrogin-1 and MuRF1). Results: Rg5 promoted C2C12 myoblast differentiation through phosphorylation of p38MAPK and MyoD/E2A heterodimerization. Furthermore, Rg5 stimulated C2C12 myotube hypertrophy via phosphorylation of Akt/mTOR. Phosphorylation of Akt induces FoxO3a phosphorylation, which reduces the expression of Atrogin-1 and MuRF1. Conclusion: This study provides an understanding of how Rg5 promotes myogenesis and hypertrophy and prevents dexamethasone-induced muscle atrophy. The study is the first, to the best of our knowledge, to show that Rg5 promotes muscle regeneration and to suggest that Rg5 can be used for therapeutic intervention of muscle weakness and atrophy, including cancer cachexia.

Ginsenoside Rg3 protects glucocorticoid­induced 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 DEX­induced myotube atrophy thereby stimulating the expression of muscle­specific genes, including myosin heavy chain and myogenin, and suppressing muscle­specific ubiquitin ligases as demonstrated by immunoblotting and immunostaining assays. Furthermore, Rg3 efficiently prevented DEX­triggered mitochondrial dysfunction of myotubes through peroxisome proliferator­activated receptor­Î³ coactivator1α activities and its mitochondrial biogenetic transcription factors, nuclear respiratory factor­1 and mitochondrial transcription factor A. These were confirmed by immunoblotting, luciferase assays, RT­qPCR 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.

Understanding of sarcopenia: from definition to therapeutic strategies.

Sarcopenia refers to the gradual loss of skeletal muscle mass and function along with aging and is a social burden due to growing healthcare cost associated with a super-aging society. Therefore, researchers have established guidelines and tests to diagnose sarcopenia. Several studies have been conducted actively to reveal the cause of sarcopenia and find an economic therapy to improve the quality of life in elderly individuals. Sarcopenia is caused by multiple factors such as reduced regenerative capacity, imbalance in protein turnover, alteration of fat and fibrotic composition in muscle, increased reactive oxygen species, dysfunction of mitochondria and increased inflammation. Based on these mechanisms, nonpharmacological and pharmacological strategies have been developed to prevent and treat sarcopenia. Although several studies are currently in progress, no treatment is available yet. This review presents the definition of sarcopenia and summarizes recent understanding on the detailed mechanisms, diagnostic criteria, and strategies for prevention and treatment.

BST204 Protects Dexamethasone-Induced Myotube Atrophy through the Upregulation of Myotube Formation and Mitochondrial Function.

BST204 is a purified ginseng dry extract that has an inhibitory effect on lipopolysaccharide-induced inflammatory responses, but its effect on muscle atrophy is yet to be investigated. In this study, C2C12 myoblasts were induced to differentiate for three days followed by the treatment of dexamethasone (DEX), a corticosteroid drug, with vehicle or BST204 for one day and subjected to immunoblotting, immunocytochemistry, qRT-PCR and biochemical analysis for mitochondrial function. BST204 alleviates the myotube atrophic effect mediated by DEX via the activation of protein kinase B/mammalian target of rapamycin (Akt/mTOR) signaling. Through this pathway, BST204 suppresses the expression of muscle-specific E3 ubiquitin ligases contributing to the enhanced myotube formation and enlarged myotube diameter in DEX-treated myotubes. In addition, BST204 treatment significantly decreases the mitochondrial reactive oxygen species production in DEX-treated myotubes. Furthermore, BST204 improves mitochondrial function by upregulating the expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) in DEX-induced myotube atrophy. This study provides a mechanistic insight into the effect of BST204 on DEX-induced myotube atrophy, suggesting that BST204 has protective effects against the toxicity of a corticosteroid drug in muscle and promising potential as a nutraceutical remedy for the treatment of muscle weakness and atrophy.