Blumea balsamifera Flavonoid-Enriched Fraction Ameliorates Lipid Disorder and Hepatic Steatosis in High-Fat-Diet-Fed Rats: Insights from Network Pharmacology, Serum Untargeted Metabolomics and Experimental Validation

Background: Blumea balsamifera (L.) DC. Is a Miao and Li ethnic medicinal plant traditionally used to activate blood circulation and dispel dampness; however, systematic investigation of its flavonoid-enriched fraction against high-fat diet (HFD)-induced lipid disorder and hepatic steatosis remains limited. Methods: A flavonoid-enriched fraction from B. balsamifera leaves (BBF, total flavonoids 30.96%) was characterised by UPLC-HRMS (83 constituents, 22 high-abundance). Network pharmacology, molecular docking, and serum untargeted metabolomics were integrated, and pivotal pathways were validated in HFD-fed rats (graded BBF doses, 55, 110, 220 mg/kg) via Western blot and RT-qPCR. Results: BBF ameliorated serum lipid abnormalities and hepatic steatosis in a dose-dependent manner; the medium-dose simultaneously improved TC, TG, LDL-C, and HDL-C levels, whereas the high-dose exerted superior triglyceride-lowering and anti-steatotic effects. Integrated two-omics analysis prioritised insulin-signalling and arachidonic acid metabolism; BBF was associated with reduced JNK hyper-phosphorylation, restored AKT activation, and decreased transcript levels of Tnf-α, Ptgs2, Srebf1, and Fasn. Conclusions: BBF alleviates HFD-induced dyslipidaemia and hepatic steatosis. This pharmacological effect is associated with coordinated modulation of inflammatory mediators, JNK/AKT signalling, and hepatic lipogenesis, as suggested by our in vivo assays and multi-omics analysis. These observations generate testable mechanistic hypotheses and provide experimental support for the traditional ethnomedicinal use of this Miao remedy.