Anti-Atrophic Effects of Dichotomine B from Stellaria dichotoma During Starvation-Induced Skeletal Muscle Atrophy

Muscle atrophy is defined as reductions in muscle size and function and represents a critical concern affecting elderly populations, immobilized patients, and individuals following specific dietary regimens, such as fasting and low-protein diets. This study investigated the protective effects of <i>Stellaria dichotoma</i> root extract and its isolated bioactive compounds during muscle atrophy using both in vitro and in vivo experimental models. First, <i>S. dichotoma</i> root extract prevented dexamethasone (DEX)-induced atrophy in C2C12 myotubes. Through systematic solvent partitioning and resin chromatography, five compounds (<b>1</b>-<b>5</b>) were successfully isolated from the <i>n</i>-butanol fraction. Dichotomine B (<b>2</b>) was identified as the most abundant and bioactive constituent. Treatment with dichotomine B significantly preserved the myotube diameter, enhanced the fusion index, and maintained the myosin heavy chain protein level while suppressing key atrophic biomarkers, including FoxO3a, MuRF-1, and Atrogin-1, in DEX-treated myotubes. Furthermore, dichotomine B (<b>2</b>) reduced proteolysis in serum-free cultured C2C12 myotubes and in mice subjected to 48 h of fasting, preserving muscle mass and strength. These findings suggest that <i>S. dichotoma</i> root extract and its principal compound, dichotomine B (<b>2</b>), have promising therapeutic potential and provide an opportunity to develop novel pharmacological interventions against muscle wasting through suppression of proteolysis pathways.