Ginsenoside Rg1 Attenuates Muscle Atrophy in Hyperglycemic Conditions, Inactivity and Protein Deprivation Models via AKT/mTOR Pathway Activation.

Abstract

Background: Muscle atrophy, a debilitating condition prevalent in diabetes and extended periods of immobilization, lacks robust therapeutic strategies. This investigation examines ginsenoside Rg1's therapeutic potential in counteracting muscle atrophy under hyperglycemic conditions and in experimental models of immobilization and dietary protein restriction.

Methods: C2C12 murine myoblasts were cultured under variable glucose concentrations and treated with or without Rg1. Multiple cellular parameters were evaluated, including cell viability, apoptotic indices, cell cycle distribution, and protein synthesis rates. The activation status of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling cascade and expression of atrophy-related markers were quantified using qRT-PCR and Western blot analyses. In parallel animal studies, rats were subjected to either immobilization or protein restriction protocols, with or without Rg1 administration. Muscle function, mass, and relevant biomarkers were evaluated.

Results: Hyperglycemic conditions significantly compromised C2C12 myoblast viability, triggered apoptotic pathways, and disrupted normal cell cycle progression. Rg1 administration effectively attenuated these detrimental effects through enhanced AKT/mTOR pathway activation, upregulation of Myogenin (MyoG) expression, and suppression of atrophy-associated markers. In the rat models, Rg1 supplementation significantly ameliorated muscle deterioration, maintaining muscle mass, contractile force, and exercise tolerance, while simultaneously modulating atrophy signaling pathways and attenuating inflammatory responses. The protective effects of Rg1 were abrogated after the co-treatment with an AKT inhibitor.

Conclusion: Ginsenoside Rg1 exhibits significant protective properties against muscle atrophy under hyperglycemic conditions and in experimental models of immobilization and protein restriction, primarily mediated through activation of the AKT/mTOR signaling pathway. These findings establish Rg1 as a promising therapeutic candidate for the treatment of muscle atrophy.