Protective effects of Aruncus dioicus leaf extract against dexamethasone-induced muscle atrophy in C2C12 myotubes

초록

Dexamethasone-induced muscle atrophy, characterized by excessive protein degradation and increased oxidative stress, represents a significant clinical challenge in patients undergoing long-term glucocorticoid therapy. Natural polyphenols have garnered increasing attention as promising therapeutic agents due to their antioxidant and anti-atrophic properties. This study investigated the protective effects of Aruncus dioicus leaf extract and its preparative fractions against dexamethasone-induced muscle atrophy in differentiated C2C12 myotubes. A 70% ethanolic extract was fractionated using preparative HPLC into two distinct fractions, F1 and F2. Phytochemical analysis revealed that F2 exhibited the highest total phenolic content, total flavonoid content, and strongest antioxidant capacity, as determined by both DPPH and ORAC assays, among all tested samples. Pretreatment with F2 significantly attenuated dexamethasone-induced myotube atrophy by preserving myotube diameter, reducing intracellular reactive oxygen species (ROS) levels, and suppressing the upregulation of the muscle-specific ubiquitin ligases muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1). UHPLC-Orbitrap MS/MS analysis demonstrated that F2 was enriched in flavonol glycosides and phenolic acids. These findings suggest that the F2 fraction of A. dioicus, which is rich in bioactive polyphenols, protects against dexamethasone-induced muscle atrophy by suppressing oxidative stress and atrogene expression.

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