Ginsenoside Ro ameliorates d-galactose-induced sarcopenia by modulating oxidative stress, inflammation, and gut microbiota in mice.

<h4>Background</h4>Sarcopenia is an age-related disorder primarily characterized by progressive muscle degeneration, and effective therapeutic interventions for this condition remain limited. Ginsenoside Ro (GRo) exhibits antioxidant and anti-inflammatory effects. However, the impact of GRo on skeletal muscle aging, myoblast differentiation, and mitochondrial dysfunction(definition) remains unexplored.<h4>Purpose</h4>The present study investigated the potential therapeutic efficacy of GRo against d-galactose (D-gal)-induced sarcopenia.<h4>Study design</h4>This study employed C2C12 myotubes and C57BL/6 N mice as in vitro and in vivo models, respectively. The ameliorative effects of GRo on sarcopenia were comprehensively elucidated through behavioral assessments, biochemical analyses, histopathological evaluation, multi-omics profiling, network pharmacology, and molecular docking.<h4>Results</h4>In cell culture experiments, GRo treatment effectively attenuated muscle atrophy and reduced senescence(definition)-associated β-galactosidase (SA-β-gal) activity. Concurrently, GRo mitigated oxidative stress by inhibiting the production of reactive oxygen species (ROS) and restoring mitochondrial membrane potential. In the animal model, administration of d-gal induced significant muscle mass loss, decreased muscle strength, and impaired exercise tolerance in mice, accompanied by elevated oxidative stress levels and systemic inflammatory responses. However, GRo treatment reversed these adverse effects, as evidenced by increased muscle mass, improved myofiber size, and enhanced physical endurance in the treated mice. Additionally, GRo supplementation increased antioxidant activity, reduced the levels of pro-inflammatory cytokines, and restored adenosine triphosphate (ATP) content. Through 16S rDNA sequencing analysis, the study revealed that GRo modulated the composition of the gut microbiota, specifically promoting the growth of beneficial microbial taxa including Akkermansiaceae, Bifidobacteriaceae, Monoglobus, Colidextribacter, and Peptococcaceae.<h4>Conclusion</h4>This study demonstrates that GRo targets the pathological mechanisms underlying age-related muscle degeneration by regulating oxidative stress, inflammatory responses, metabolic processes, and gut microbiota homeostasis.