基于网络药理学和分子对接探讨金银花改善2型糖尿病的潜在机制

Potential Mechanism of Honeysuckle in the Improving of Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking

摘要: 目的：运用网络药理学和分子对接的方法探讨金银花改善2型糖尿病(type 2 diabetes mellitus, T2DM)的潜在机制。方法：通过检索中药系统药理学数据库与分析平台(TCMSP)获得金银花的有效成分及活性靶点，通过比对人类基因数据库(GeneCards)归纳总结金银花中具有治疗作用的核心靶点，运用String10.5构建核心靶点相互作用网络图。Cytoscape3.6.1软件绘制成分–靶点和蛋白质相互作用网络图。使用DAVID6.8数据库对核心靶点进行基因本体(GO)分析和基因百科全书(KEGG)通路富集分析。AutoDockTools1.5.6进行分子对接验证关键成分与核心靶点的结合活性。结果：获得金银花有效成分17种，活性靶点204个，与T2DM相关的靶点68个。其中，槲皮素、山奈酚、木犀草素、β-谷甾醇和豆甾醇可能是金银花改善T2DM的主要活性成分，TNF、AKT1、IL6、MAPK1、VEGFA可能是治疗的关键靶点，HIF-1、TNF、PI3K-AKT、FoXO信号通路可能与改善T2DM相关。分子对接结果显示，主要活性成分与关键靶点结合良好。结论：网络药理学和分子对接在研究金银花改善T2DM的作用机制中发挥作用，并为进一步探索提供理论参考。

Abstract: Objective: To explore the potential mechanism of Honeysuckle in improving type 2 diabetes mellitus (T2DM) based on network pharmacology and molecular docking. Methods: The effective components and active targets of Honeysuckle were obtained by using the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). By comparing with the human gene database (GeneCards), the core targets with therapeutic effect in Honeysuckle were summarized. And the String10.5 was used to construct target interaction network. Cytoscape3.6.1 software was used to plot the component-target network and protein interaction network. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the core targets were performed by using the David6.8 database. AutoDockTools1.5.6 conducted molecular docking to verify the binding activity between key components and core targets. Result: 17 active components, 204 active targets and 68 targets related to type 2 diabetes were obtained from Honeysuckle. Quercetin, Kaempferol, Luteolin, β-sitosterol and Stigmasterol may be the main active components of Honeysuckle in improving T2DM. TNF, AKT1, IL6, MAPK1 and VEGFA may be the key targets of treatment. HIF-1, TNF, PI3K-AKT and FoXO signaling pathways may be related to the improvement of T2DM. The results of molecular docking showed that the main active components were well combined with the key targets. Conclusions: Network pharmacology and molecular docking play roles in exploring the potential mechanism of Honeysuckle in improving T2DM, and provide theoretical reference for further research.