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image of Metabolomics and Network Pharmacology Analyses 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 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 multi-metabolite, multi-target mechanism of YD distinguishes it apart from single-target drugs, such as metformin. The binding of luteolin to EGFR may potentially reactivate the PI3K-Akt signaling pathway, thereby enhancing insulin sensitivity. Regulation of metabolic pathways, including the biosynthesis of unsaturated fatty acids, contributes to the reduction of hepatic lipid deposition. These findings underscore the capacity of YD to disrupt the IR-ELD cycle in T2DM.

Conclusion

YD ameliorates T2DM-IR and hepatic ELD by modulating EGFR signaling and metabolic pathways, providing multi-omics evidence for its clinical application.

© 2025 Bentham Science Publishers
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2025-09-24
2025-11-05

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Metabolomics and Network Pharmacology Analyses of Yiqi Huazhuo Decoction in Regulating EGFR Signaling and Metabolic Pathways in Type 2 Diabetes with Insulin Resistance: In Vivo Validation
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  • Article Type:     Research Article
Keywords: Yi qi huazhuo decoction ; type 2 diabetes ; hepatic ectopic lipid deposition ; molecular docking ; metabolomics ; EGFR ; insulin resistance

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