OBJECTIVE  To investigated the material basis and underlying mechanism of Jiangzhuo decoction(JZD) in the treatment of type 2 diabetes mellitus(T2DM) by in vivo experiments, metabolomics and network pharmacology.

METHODS  A T2DM mouse model was constructed using a high-fat diet combined with streptozotocin. Mice were treated with metformin or low/medium/high doses of JZD for 8 weeks. Serum biochemical parameters, renal histopathology(HE and PAS staining), and renal protein expression(ELISA) were analyzed. Liver metabolomic profiles were assessed. Components of JZD were screened via Q-TOF-LC-MS and the TCMSP database. Potential targets of JZD and T2DM-related genes were predicted via SwissTargetPrediction, GeneCards, and OMIM databases. Common targets were used to construct a "herb-compound-target" network. STRING and Metascape were employed for protein-protein interaction(PPI) network and pathway enrichment analysis. Molecular docking validation was performed using AutoDock Vina.

RESULTS  JZD significantly improved glucose-lipid metabolism and alleviated renal injury in T2DM mice by reversing hepatic metabolic disturbances, as demonstrated through metabolomics analysis. Network pharmacology identified 260 common targets, with AGE-RAGE signaling as a key enriched pathway. Molecular docking confirmed strong binding between core components(daidzein, puerarin, etc.) and critical targets(IL-6, TNF-α, etc.). Animal experiments validated JZD’s inhibition of the AGE-RAGE axis and downstream inflammatory cytokine release.

CONCLUSION  JZD ameliorates hyperglycemia and insulin resistance in T2DM mice via regulating hepatic metabolic homeostasis and inhibiting inflammation, providing a mechanistic basis for its clinical translation.