Abstract
Sarcopenia is an age-related decline in skeletal muscle mass and function that is closely associated with oxidative stress and excessive glucocorticoid exposure. This study investigated the protective effects of a Pueraria lobata extract powder (PEP) in C2C12 myotubes. PEP was standardized to 4.17% puerarin. PEP pretreatment significantly improved cell viability and suppressed the intracellular accumulation of reactive oxygen species under hydrogen peroxide-induced oxidative stress, while restoring the levels of glutathione and reducing apoptosis. Furthermore, in dexamethasone-treated myotubes, PEP pretreatment prevented myotube shrinkage, downregulated the E3 ubiquitin ligases Atrogin-1 and MuRF1, and upregulated the myogenic markers MyoD and myogenin. Mechanistically, PEP restored the phosphorylation of Akt and mTOR while enhancing the inhibition of FoxO3a phosphorylation, thereby promoting anabolic and suppressing catabolic signaling. These findings suggest that PEP serves dual protective functions through redox modulation and muscle protein metabolism regulation. This study provides in vitro evidence that a puerarin-rich P. lobata extract can concurrently mitigate oxidative stress and glucocorticoid-induced muscle atrophy, thus supporting its potential as a multi-targeted nutraceutical candidate for preventing muscle wasting and sarcopenia.