Trichosanthes kirilowii Maximowicz attenuates dexamethasone induced atrophy in C2C12 myotubes through a Sirtuin 1 associated mechanism.

Glucocorticoids such as dexamethasone (DEX) are commonly used clinically but can induce skeletal muscle atrophy with prolonged or high-dose exposure. Trichosanthes kirilowii Maximowicz (TK), a traditional medicinal herb, has known pharmacological effects, but its impact on muscle atrophy remains unclear. This study investigated the anti-atrophic potential of TK in DEX-induced muscle atrophy models. In C2C12 cells, TK improved cell viability and restored myotube diameter and number, downregulated atrophy markers MuRF-1 and Atrogin-1, and upregulated myogenic markers MyoD, MyoG, and MHC. TK also restored Sirtuin 1 (SIRT1) expression suppressed by DEX, and inhibition of SIRT1 with EX527 reduced TK's beneficial effects, indicating a SIRT1-dependent mechanism. TK rescued DEX-induced reductions in phosphorylated AKT and mTOR, supporting its role in muscle anabolism. In vivo, oral TK administration attenuated DEX-induced weight loss, preserved gastrocnemius muscle mass, and improved motor performance. Molecular docking analysis revealed that key TK-derived compounds, including 5-dehydrokarounidiol, steryl glucoside, and isomultiflorenol, exhibited moderate binding affinity (- 6.3 to - 6.6 kcal/mol) toward the allosteric site of SIRT1. These findings suggest that TK protects against muscle atrophy by modulating SIRT1-related anabolic and catabolic pathways. TK may offer therapeutic potential for sarcopenia and glucocorticoid-induced muscle wasting.