<i>Siegesbeckia Glabrescens</i> Extract Ameliorates Immobilization‐Induced Muscle Atrophy by Regulating the Akt/ <scp>mTOR</scp> / <scp>FoxO3a</scp> Signaling Pathways in Mice

<i>Siegesbeckia glabrescens</i>, traditionally used for its anti-inflammatory properties and potential musculoskeletal benefits. In the present study, we investigated whether a standardized hot water extract of <i>S. glabrescens</i> (SGE), rich in the bioactive compound kirenol, could mitigate muscle atrophy caused by immobilization in a mouse model. Male C57BL/6J mice underwent hindlimb immobilization for 1 week to induce muscle atrophy, followed by 1 week of daily oral treatments with either saline or SGE (150 or 300 mg/kg/day). SGE significantly prevented the decline in muscle mass (5.1%-22.7%, <i>p</i> < 0.05), strength (26.0%-36.6%, <i>p</i> < 0.05), volume, and muscle fiber cross-sectional area (21.6%-29.8%, <i>p</i> < 0.05) caused by immobilization. In the tibialis anterior muscle, SGE mitigated immobilization-induced elevations in protein degradation markers, including muscle RING-finger protein-1 and muscle atrophy F-box, by inhibiting the nuclear translocation of forkhead box O3a. Also, SGE countered reductions in protein synthesis indicators, including mammalian target of rapamycin, 70-kDa ribosomal protein S6 kinase, and 4E binding protein 1, through activation of the phosphatidylinositol 3-kinase/Akt pathway. Furthermore, kirenol attenuated tumor necrosis factor-alpha-driven muscle atrophy in L6 myotubes by modulating both protein synthesis and degradation processes. Collectively, these findings suggest that SGE containing kirenol maintains the equilibrium between protein degradation and protein synthesis, thereby ameliorating immobilization-induced muscle atrophy.