Mechanistic Investigation of Huanglian-Wumei in Diabetes Treatment: Integration of LC-MS, Network Pharmacology, and Molecular Docking Approaches

Background: Huanglian and Wumei, traditional herbal medicines with a long history of use, are reported to exhibit antidiabetic properties, though their precise mechanisms remain elusive. Purpose: This study aims to delineate the therapeutic targets and effects of the Huanglian-Wumei combination in diabetes treatment through network pharmacology, molecular docking, and animal experiments. Methods: UPLC-Q-TOF-MS was utilized to identify the major constituents of the herbal pair, with target prediction conducted via TCMSP and Swiss Target Prediction databases. A PPI network was constructed, followed by GO functional and KEGG pathway enrichment analyses to explore the mechanism of action. Molecular docking simulations were performed using AutoDock Tools, and a mouse model of acute diabetes was established to evaluate blood glucose levels, glucose tolerance, biochemical markers, and pancreatic histopathology, verifying antidiabetic efficacy. Results: Among 1169 compounds, 50 were prioritized, revealing 208 diabetes-associated targets. Core targets included GAPDH, TNF, AKT1, IL-6, and ALB, with critical active components identified as 8-Oxyberberine, Berberine, Quinic acid, and Corydine. These components may exert their effects by insulin signaling pathway, AGE-RAGE signaling pathway, and TNF signaling pathway were implicated in the study. Molecular docking analysis showed that the core active compounds effectively bound to the key targets, suggesting strong interactions. Animal data demonstrated reductions in FBG, OGTT, INS, TC, TG, LDL-C, MDA, TNF-α, IL-6, and CRP levels, alongside increased HDL-C, SOD, and GSH levels ( P < .05 or P < .01). These findings indicated pancreatic protection in diabetic mice. Conclusions: Huanglian – Wumei herb pair has some therapeutic effects on diabetes mellitus, and it is predicted that its active ingredients may act mainly through the AGE-RAGE signalling pathway, insulin pathway, etc, and provide new insights into diabetes mellitus treatment.