Metabolomics and Network Pharmacology Analysis of Yiqi Huazhuo Decoction in Regulating EGFR Signaling and Metabolic Pathways in Type 2 Diabetes with Insulin Resistance: In Vivo Validation
Abstract
INTRODUCTION: Type 2 diabetes mellitus (T2DM), characterized by insulin resistance (IR) and hepatic ectopic lipid deposition (ELD), poses a complex metabolic challenge. This study aimed to elucidate the mechanisms of Yiqi Huazhuo Decoction (YD) through an integrated approach combining network pharmacology and metabolomics. T2DM is marked by impaired insulin signaling and disrupted hepatic lipid metabolism, resulting in a vicious cycle that accelerates disease progression. While Traditional Chinese Medicine (TCM), such as YD, demonstrates potential in modulating these dysfunctions, its underlying molecular mechanisms remain to be fully clarified.
MATERIALS AND METHODS: A diabetic fat rat model was used to evaluate the efficacy of YD. UPLC-MS characterized the main metabolites found in YD. After an 8-week intervention, physiological indices and hepatic pathology were assessed. Network pharmacology identified bioactive metabolites and targets, which were validated by molecular docking. Untargeted metabolomics was employed to analyze hepatic metabolic changes.
RESULTS: YD improved glucose/lipid metabolism, insulin sensitivity, and hepatic function. Network pharmacology revealed that YD acts via the EGFR and PI3K-Akt/IL-17 pathways. Molecular docking confirmed luteolin-EGFR binding. Metabolomics identified 20 altered metabolites in the biosynthesis of unsaturated fatty acids. Multi-omics analysis revealed that YD regulated EGFR and hepatic metabolic networks.
DISCUSSION: The…
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