A Study on the Mechanism of Action of Hyperoside in Treating Type 2 Diabetes: Integrating Metabolomics, Network Pharmacology, Molecular Docking, and Experimental Validation.

Type 2 diabetes mellitus (T2DM), a chronic metabolic disorder caused by genetic and environmental factors, is characterized by insulin resistance and impaired pancreatic β-cell function. Hyperoside, a natural flavonol glycoside, exerts anti-T2DM effects, but its mechanism remains unclear. This study established T2DM mouse models via a high-fat/high-sugar diet and streptozotocin injection, detecting body weight, blood glucose, and biochemical indicators. Combined metabolomics, network pharmacology, in-vitro experiments, and molecular docking were used to explore its therapeutic targets and mechanisms. Pharmacodynamic studies confirmed hyperoside's hypoglycemic and symptom-improving effects. Nontargeted metabolomics identified 15 diabetes-related biomarkers, revealing hyperoside may regulate primary bile acid biosynthesis and glycerophospholipid metabolism via specific targets. Network pharmacology screened 161 core targets, with SRC, PTPN11, and EGFR as key ones via KEGG enrichment analysis. Molecular docking verified hyperoside's favorable binding affinity to these targets. In conclusion, hyperoside has a good therapeutic effect on T2DM, possibly by regulating the above metabolic pathways.