Crocetin Alleviates Ovariectomy-Induced Metabolic Dysfunction through Regulating Estrogen Receptor β

Metabolic dysfunction (MD) is a major health problem threatening the life quality of menopausal women. Saffron has been widely used in herb prescriptions for treating menopausal syndrome. However, the pharmacological effects and mechanisms of saffron are poorly understood. Here, we investigated the effect of crocin, the major ingredient of saffron and its active metabolite in blood, crocetin, on MD and lipid metabolism in ovariectomized (OVX) mice and 3T3-L1 adipocytes. The present study showed that intragastric treatment of crocin prevented weight gain, fat accumulation, and insulin resistance in OVX mice by increasing energy expenditure and fat oxidation. Mechanistically, crocin influenced adipose tissue homeostasis by regulating adipogenic and lipolytic factors, which was strongly associated with the restoration of the downregulated ERβ function in white adipose tissue (WAT). In vitro, crocetin facilitated lipid metabolism in an ERβ-dependent manner. Our results demonstrated the beneficial effects of crocetin/crocin-mediated intervention against metabolic dysfunction, revealing a prospective therapeutic application in menopausal women.