Pro-myogenic and anti-atrophic effects of Padina arborescens extract through Akt/mTOR signaling in dexamethasone-induced C2C12 cells and zebrafish model.

Abstract

Muscle atrophy, which is characterized by the loss and dysfunction of skeletal muscle proteins, is a major degenerative condition that is associated with aging and glucocorticoid therapy. Marine-derived compounds, particularly polyphenols, have recently potential in modulating muscle metabolism and regeneration. This study aimed to investigate the effects of the ethanolic extract from Padina arborescens (PAE) on myogenic differentiation and dexamethasone (DEXA)-induced muscle atrophy using C2C12 myotubes and a zebrafish model. PAE treatment significantly promoted myotube differentiation by modulating the Akt/mTOR signaling pathway and enhancing the expression level of myogenic regulatory factors (MyoD and myogenin). In DEXA-treated myotubes, PAE effectively suppressed the ubiquitin proteasome system, restored myosin heavy chain protein synthesis, and recovered myotube morphology. In vivo, PAE supplementation ameliorated the DEXA-induced locomotor dysfunction in zebrafish without causing developmental or neurotoxic abnormalities, as confirmed by the normal survival rate, body length, and heart rate. Collectively, these findings indicated that polyphenol-rich PAE exerts protective and anabolic effects by promoting myogenesis and preventing glucocorticoid-induced muscle degradation. Therefore, PAE may be used as a promising marine-derived therapeutic agent for maintaining skeletal muscle health and preventing muscle atrophy.