An Integrated Study Based on UPLC-QTOF/MS Network Pharmacology and In Vivo Validation of the Anti-Obesity Effects of the 60% Ethanol-Eluted Fraction from Rheum tanguticum

Obesity has emerged as a significant global public health challenge, yet the clinical utility of existing anti-obesity drugs is often constrained by limited efficacy and adverse safety profiles. Rheum tanguticum Maxim. ex Balf., a traditional medicinal plant, has shown potential in modulating glucose and lipid metabolism; however, its specific anti-obesity mechanisms remain poorly characterized. In this study, the chemical profile of the 60% ethanol-eluted fraction of R. tanguticum (RTE) was characterized via UPLC-QTOF/MS, followed by network pharmacology analysis to predict regulatory targets and enriched pathways. Subsequently, a high-fat diet (HFD)-induced obese mouse model was established to evaluate the anti-obesity effects of RTE by monitoring body weight, Lee’s index, fat-to-body weight ratio, serum lipid profiles, and liver histopathological changes. A total of 14 major compounds, primarily anthraquinone glycosides, were identified. Integrated network analysis identified 10 hub targets, including TNF, EGFR, and TP53. In vivo experiments demonstrated that RTE significantly attenuated body weight gain and reduced Lee’s index, fat-to-body ratios, and serum levels of TC, TG, and LDL-C. Furthermore, RTE treatment markedly alleviated hepatic steatosis and inflammatory infiltration in obese mice. These findings suggest that RTE exerts potent anti-obesity effects through a multi-target and multi-pathway mechanism that regulates lipid metabolism and suppresses inflammation. This study improves our understanding of the pharmacological value of R. tanguticum and provides a scientific basis for its development as a functional food ingredient or therapeutic agent against obesity.