Exploration of the Potential Mechanism of Yiwei Decoction in the Treatment of Type Ⅱ Diabetes Mellitus Based on GEO Gene Chip, Network Pharmacology and Molecular Docking Technology

Objective To explore the potential mechanism of Yiwei decoction in treating T2DM by using GEO gene chip data combined with network pharmacology and molecular docking technology, and to provide reference for further basic research. Methods The active components and targets of yiwei decoction were screened from databases of TCMSP and BATMAN-TCM based on oral availability and Drug-like properties , we combined GeneCards, OMIM, Pharmgkb, TTD and DrugBank to search the target genes of T2DM. The software cytoscape 3.7.2 constructed the drug-component-target gene network to screen the core compounds The protein interaction analysis network was established by using String database, and the core protein targets were selected by cytoscape 3.7.2 topology analysis. Gene ontology (GO) function and KEGG (KEGG) pathway enrichment were analyzed using Metascape database, and molecular docking was visualized using autodock 3.7.2 and PyMol 2.1.1. Results 7577 targets of T2DM were selected, 38 active components of Yiwei decoction were identified, and the core components were γ-aminobutyric acid, quercetin, Kaempferol, β-sitosterol, etc. 191 potential effective targets were predicted, which involved PI3K-Akt, MAPK, HIF-1, RAP1, JAK-STAT and other pathways to treat T2DM. The chemical binding energy of EFGR, PPARG and ILIB to the active components was lower than -8 kcal/mol. Conclusion The active components of yiwei decoction may bind to EFGR, PPARG, ILIB and regulate HIF-1, MAPK, PI3K-Akt signal pathway to treat T2DM.

目的 本研究拟利用GEO基因芯片（Gene Expression Omnibus gene chip）数据结合网络药理学与分子对接技术，探讨益胃汤（Yiwei decoction）治疗2型糖尿病（Type 2 Diabetes Mellitus, T2DM）的潜在作用机制，为后续基础研究提供参考依据。
方法 基于口服生物利用度与类药性（Drug-like properties）标准，从TCMSP与BATMAN-TCM数据库中筛选益胃汤的活性成分及作用靶点；结合GeneCards、OMIM、Pharmgkb、TTD及DrugBank数据库检索2型糖尿病的相关靶基因。使用Cytoscape 3.7.2软件构建“药物-成分-靶基因”调控网络以筛选核心活性化合物；通过String数据库构建蛋白质相互作用分析网络，并借助Cytoscape 3.7.2进行拓扑分析以获取核心蛋白靶点。利用Metascape数据库开展基因本体（Gene Ontology, GO）功能富集分析与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）通路富集分析；采用AutoDock 3.7.2与PyMOL 2.1.1软件完成分子对接结果的可视化处理。
结果 本研究共筛选得到7577个2型糖尿病相关靶基因，鉴定出38个益胃汤活性成分，核心活性成分包括γ-氨基丁酸、槲皮素、山奈酚、β-谷甾醇等；预测得到191个潜在有效作用靶点，其涉及PI3K-Akt、MAPK、HIF-1、RAP1、JAK-STAT等多条信号通路以发挥2型糖尿病治疗作用。EFGR、PPARG及ILIB与活性成分的化学结合能均低于-8 kcal/mol。
结论 益胃汤的活性成分可通过结合EFGR、PPARG、ILIB靶点，调控HIF-1、MAPK、PI3K-Akt信号通路，进而发挥治疗2型糖尿病的作用。