Amino acid (Leu, Gln, Cys)–EGCG mixture mitigates dexamethasone-induced muscle atrophy via PI3K-Akt-mTOR and SIRT1-PGC1α pathway regulation

Glucocorticoid-associated skeletal muscle wasting poses a significant clinical issue, stemming from a dysregulation between the synthesis and breakdown of muscle protein. To investigate potential countermeasures, we examined the effects of an amino acid–epigallocatechin gallate mixture (AA–EGCG), composed of cysteine, glutamine, leucine, and EGCG, in dexamethasone (DEX)-treated C2C12 myotubes and C57BL/6 mice. DEX administration induced pronounced muscle atrophy, with reduced myotube size, suppressed expression of myogenic and anabolic markers (MyoD1, myogenin, PI3K/Akt/mTOR), and activation of catabolic mediators (FoxO3a, MuRF1, Atrogin-1). Mitochondrial biogenesis and antioxidant signaling were also impaired via downregulation of the SIRT1–PGC1α axis. The AA–EGCG effectively mitigated DEX-triggered muscle atrophy, showing a concentration-dependent effect. It preserved myotube morphology, enhanced myogenic differentiation, restored PI3K/Akt/mTOR signaling, and suppressed FoxO3a-mediated proteolysis. Moreover, it upregulated SIRT1, PGC-1α, and related regulators, thereby enhancing mitochondrial function and defense against oxidative. In vivo , AA–EGCG further prevented muscle mass loss, normalized serum biomarkers, and improved physical performance in DEX-treated mice. Collectively, these findings identify AA–EGCG as a multi-targeted nutritional strategy that mitigates glucocorticoid-induced muscle wasting by coordinating anabolic, catabolic, and mitochondrial pathways.