A flavonoid-rich medicinal herb extract ameliorates high-fat diet-induced obesity and insulin resistance in mice

Obesity has emerged as a critical global health challenge, contributing to severe metabolic and neoplastic complications. However, most existing anti-obesity drugs exhibit significant adverse effects, necessitating the development of safer therapeutic alternatives. In this study, we evaluate the efficacy and safety of a flavonoid-rich medicinal herb extract (MHE) in a high-fat diet (HFD)-induced murine obesity model. Daily oral administration of MHE does not alter food intake or induce hepatic injury but significantly attenuates HFD-induced weight gain (P < 0.05) and adiposity accumulation. Furthermore, MHE treatment improves systemic insulin sensitivity and glycemic control. Notably, MHE enhances whole-body energy expenditure, as evidenced by elevated oxygen consumption (VO2), carbon dioxide production (VCO2), and heat generation (P < 0.01). Mechanistically, MHE selectively promotes the proliferation of beneficial gut microbiota, including Lactobacillus, Akkermansia, and Bifidobacterium species, resulting in increased production of the short-chain fatty acid propionate (PA). Elevated circulating PA levels subsequently stimulate the browning/beiging of inguinal white adipose tissue (iWAT) and upregulate thermogenic pathways. Collectively, our findings demonstrate that MHE exerts anti-obesity effects through gut microbiota modulation and adipose tissue remodeling, offering a promising natural alternative for obesity management.