From Myotubes to Skeletal Muscle: Cimicifuga racemosa Extract Ze 450 Preserves Muscle Mass and Affects Skeletal Muscle Energy Metabolism Under Conditions of Metabolic Stress

Preservation of skeletal muscle is an important consideration when evaluating weight-loss interventions, particularly during menopause, when adverse changes in body composition occur. We investigated the effects of Cimicifuga racemosa extract Ze 450 on skeletal muscle. Differentiated C2C12 myotubes were treated with Ze 450, dexamethasone (DEX), or their combination. Non-ovariectomized female Wistar rats were assigned to one of five groups: standard diet, high-fat diet (HF), HF plus voluntary running, HF plus Ze 450 (130 mg/kg/day), or HF plus Ze 450 and voluntary running. Muscle mass and fiber cross-sectional area (CSA) were assessed in the predominantly glycolytic gastrocnemius and oxidative soleus. Markers of mitochondrial content (COX IV and CS), lipid metabolism (ATGL, HSL, FAS, and SREBP-1c), glucose transport (GLUT4), and myogenic signaling (IGF-1) were analyzed. Ze 450 had limited effects on myotube diameter under basal conditions but significantly attenuated DEX-induced myotube atrophy. In vivo, Ze 450 reduced body weight gain and fat accumulation without reducing muscle mass or fiber CSA. Ze 450 differentially affected metabolic markers in the two muscle types, decreasing markers associated with mitochondrial content in the soleus while increasing mitochondrial markers in the gastrocnemius. Taken together, these findings suggest a potential role for Ze 450 in rebalancing skeletal muscle metabolism in a muscle-type-specific manner while preserving skeletal muscle during reductions in body weight gain and adiposity.