Exercise-associated and metabolic effects of Cimicifuga racemosa extract Ze 450 in a high-fat diet model in female rats

Background Physical inactivity and high-calorie diets are major drivers of obesity and metabolic disease. In a previous pilot study under physiological dietary conditions, Cimicifuga racemosa extract Ze 450 reduced visceral adiposity and leptin levels in female rats, suggesting exercise-like metabolic effects. Whether these effects persist under diet-induced metabolic stress remains unclear. This study investigated whether Ze 450 exerts exercise-associated metabolic effects in a high-fat (HF) diet model. Methods Non-ovariectomized female Wistar rats (n = 30) were randomized to standard diet (SD), HF, HF + Ze 450 (130 mg/kg), HF + voluntary running activity, or HF + Ze 450 + activity (n = 6/group) for 12 weeks. Activity groups had nightly access to running wheels. Visceral fat mass, adipocyte morphology, glucose tolerance, serum leptin and cholesterol levels, and expression of metabolic genes ( Fasn, Cebpa, Abca1, Cyp7a1 ) were assessed. Results HF feeding induced body weight gain, visceral fat accumulation, adipocyte hypertrophy, hyperleptinemia, and impaired glucose tolerance. Ze 450 treatment and running activity antagonized the HF-induced increases in body and visceral fat mass, attenuated HF diet-induced impairments in glucose handling, lowered leptin levels, and modulated metabolic gene expression. While the physiological effects of Ze 450 were comparable to exercise, molecular analyses revealed distinct regulatory patterns. Conclusion Ze 450 mitigated key features of HF diet-induced metabolic dysfunction and demonstrated exercise-like physiological effects in a metabolically challenged model. Despite mechanistic differences from classical exercise-induced adaptations, the overall phenotype supports discussion of Cimicifuga racemosa extract Ze 450 as a plant-derived metabolic modulator with exercise-associated properties.