Cryptotaenia japonica extract attenuates glucocorticoid-induced muscle atrophy via regulation of the AKT/mTOR-FOXO/E3 ubiquitin ligase axis.

Sarcopenia, characterized by progressive loss of skeletal muscle mass and function, is exacerbated by chronic glucocorticoid exposure, which activates catabolic signaling pathways and accelerates muscle protein degradation. Although Cryptotaenia japonica Hassk (Apiaceae) has been reported to possess antioxidant and anti-inflammatory properties, its role in glucocorticoid-induced muscle atrophy remains unclear. In this study, we investigated the myoprotective effects of Cryptotaenia japonica extract (CJE) using both in vitro and in vivo models. C2C12 myotubes were treated with dexamethasone (Dex, 10 μM) in the presence or absence of CJE (10-100 μg/mL), and key signaling pathways were analyzed by Western blotting and confocal microscopy. In vivo, Dex-induced muscle atrophy was established in ICR mice, followed by oral administration of CJE (200 mg/kg/day). Muscle tissues were evaluated for protein expression, histological alterations, and serum GDF-8 levels. CJE treatment attenuated Dex-induced upregulation of the E3 ubiquitin ligases MuRF-1 and FBX32 and inhibited FOXO1 nuclear translocation in C2C12 myotubes. In dexamethasone-treated mice, CJE restored mTOR phosphorylation and normalized the dexamethasone-induced dysregulation of AKT phosphorylation, while suppressing the FOXO/E3 ubiquitin ligase catabolic axis. In Dex-treated mice, CJE reduced the expression of FOXO3a, MuRF-1, and FBX32, preserved muscle fiber architecture, and increased muscle fiber cross-sectional area. Furthermore, CJE modulated circulating GDF-8 levels associated with muscle atrophy. Collectively, these findings demonstrate that CJE mitigates glucocorticoid-induced muscle atrophy by coordinately regulating the AKT/mTOR-FOXO/E3 ubiquitin ligase signaling axis. These results suggest that CJE may serve as a promising natural therapeutic candidate for the prevention of sarcopenia and muscle-wasting conditions.