Sarcopenia, characterized by declines in skeletal muscle mass, strength, and physical function, is driven by elevated oxidative stress, chronic inflammation, and imbalances in protein homeostasis. Effective therapeutic interventions without side effects targeting these factors are crucial for older adults. Since Cudrania tricuspidata leaf extract (CTE) exhibits antioxidant and anti-inflammatory activities, this study aimed to investigate the effects of CTE on dexamethasone (Dex)-induced muscle atrophy in C2C12 myotubes. CTE exhibited strong antioxidant capacity, as evidenced by its DPPH and ABTS radical scavenging activities, along with high total phenolic and flavonoid contents. HPLC analysis identified chlorogenic acid, isoquercetin, and kaempferol-3-glucoside as its major bioactive polyphenols. Dex reduced myotube length and diameter, whereas CTE treatment recovered them, as demonstrated by Jenner-Giemsa and immunofluorescence staining. CTE improved protein homeostasis by increasing the protein synthesis markers p-mTOR and p-Akt and decreasing the protein degradation marker MuRF1, compared with the Dex-treated group, indicating that it promotes synthesis while inhibiting breakdown. Molecular docking analysis suggested stable binding of chlorogenic acid and kaempferol-3-glucoside to glucocorticoid receptor (GR). This was further corroborated by downstream gene expression analysis of Redd1 and Klf15, which are transcriptional targets of GR. While Dex upregulated these genes, CTE significantly suppressed their expression, indicating mitigation of muscle atrophy via GR modulation. These findings suggest CTE may serve as a natural therapeutic agent for skeletal muscle health.
Jeong et al. (2026) studied this question.