Abstract
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.
Highlights
The progressive loss of skeletal muscle mass and strength is a hallmark of muscle aging, leading to reduced functional capacity and an increased risk of developing chronic metabolic diseases [1,2]
We found that BST204 improves myotube formation by activating Akt/mTOR signaling in DEX-treated myotubes and enhances PGC1α-mediated mitochondrial function to prevent DEX-triggered myotube atrophy
BST204 dramatically upregulated Akt activation, as evidenced by greatly enhanced levels of the phosphorylated forms (p-Akt) (Figure 1d). These data indicate that BST204 induces myotube hypertrophy, which is dependent on the activation of Akt signaling to enhance myoblast differentiation
Summary
The progressive loss of skeletal muscle mass and strength is a hallmark of muscle aging, leading to reduced functional capacity and an increased risk of developing chronic metabolic diseases [1,2]. Muscle atrophy is triggered by an imbalance between protein synthesis and protein degradation by the ubiquitin-proteasome system (UPS), resulting in a decrease in muscle fiber size [3]. Muscle RING finger containing protein 1 (MuRF1) and Atrogin-1 are major muscle-specific E3 ubiquitin ligases associated with protein degradation in muscle cells [4,5] and are high-fidelity markers of the muscle atrophy phenotype [6]. In addition to the imbalance in protein metabolism, the decreased regenerative capacity of muscle stem cells is tightly associated with the loss of muscle mass and function resulting from aging or age-related muscle diseases [3,7].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
