Myoprotective Role of Quercus acuta Thunb. Fruit Extract Through IGF-1–Akt–FOXO Axis Modulation in Dexamethasone-Induced Sarcopenia

Sarcopenia, characterized by the progressive loss of skeletal muscle mass and function, is exacerbated by glucocorticoid exposure. Although there is growing interest in natural therapies for muscle atrophy, the effects of Quercus acuta Thunb. fruit extract (QA) on sarcopenia or glucocorticoid-induced muscle loss had not been previously investigated. QA is an evergreen oak known for its antioxidant and anti-inflammatory properties, with polyphenolic components reported to enhance oxidative and metabolic homeostasis in various tissues. Based on these properties, we hypothesized that QA could counteract muscle atrophy by modulating anabolic and catabolic signaling pathways. The research utilized both in vitro (C2C12 myotubes) and in vivo (ICR mice) models to assess QA’s effects. Daily oral administration of QA (100–200 mg/kg) was given to mice with dexamethasone (Dex)-induced muscle atrophy. Techniques included H&E staining to assess muscle mass and fiber cross-sectional area (CSA), Western blot, and ELISA analyses to investigate signaling pathways. Confocal imaging was also used to confirm cellular changes. In vitro QA treatment improved myotube integrity by increasing myogenic differentiation markers (MyoD, MyoG) and suppressing atrophy-related E3 ligases, specifically MuRF-1 and FBX32/Atrogin-1. Confocal imaging showed that QA inhibited the nuclear localization of FOXO1 and reduced FBX32 expression. In vivo, daily oral administration of QA significantly preserved gastrocnemius muscle mass and fiber cross-sectional area in Dex-treated mice. QA restored the IGF-1/PI3K/Akt signaling pathway and attenuated FOXO1-dependent proteolytic activation. Collectively, these findings demonstrate that QA possesses potent anti-atrophic and myoprotective effects mediated through the modulation of the IGF-1/Akt-FOXO axis. QA has potential as a novel natural therapeutic for preventing glucocorticoid-induced sarcopenia.