基于网络药理学研究六味地黄丸干预二型糖尿病作用机制

Study on the Mechanism of Liuweidihuang Pills in the Intervention of Type 2 Diabetes Mellitus Based on Network Pharmacology

目的:采用网络药理学的方法,探究六味地黄丸干预2型糖尿病潜在的活性成分和作用机制。方法:从中药系统药理学数据库及分析平台(TCMSP)数据库,通过Swiss Target Prediction数据库预测和筛选出活性成分的潜在的作用靶点,通过权威数据库(Drugbank、OMIM、TTD、CTD)检索T2DM相关靶点,将预测的潜在靶点和糖尿病相关靶点绘制韦恩图得到两者的共同靶点作为六味地黄丸干预T2DM的靶点,并通过Cytoscape 3.2.1软件建立成分-靶点网络模型进行网络分析。将核心靶点导入到STRING在线数据库进行蛋白互作(PPI)网络构建并进行分析。利用David数据库进行基因本体(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析,阐明六味地黄丸成分对疾病的作用机制。结果:筛选出六味地黄丸37个活性成分,共预测出148个潜在靶点;找到和T2DM相关靶点共57个,这些关键靶点涉及的通路包括糖尿病并发症通路、胰岛素抵抗、炎症通路、氧化应激通路。结论:六味地黄丸可能是通过糖尿病并发症通路、胰岛素抵抗、炎症通路、氧化应激通路干预糖尿病。本研究为阐明中药经典名方六味地黄丸的药理活性及其作用机制研究提供了可靠的科学依据。

Objective:To predict the potential active components in Liuwei Dihuang pills by the network pharmacology,and map the related targets of type 2 diabetes.Methods:Firstly,the main active components of Liuwei Dihuang pills were screened out from TCMSP based on the pharmacokinetic characteristics,and the related targets were predicted by Pubchem and Swiss Target Prediction.The predicted potential targets and diabetes-related targets were drawn to obtain a Venn diagram to get the common targets of them as the targets of Liuwei Dihuang pills for the intervention with type 2 diabetes by searching authoritative databases(Drugbank,OMIM,TTD,and CTD)to find type 2 diabetes-related targets.And then the core targets were imported into STRING database to build the protein interaction network graph.Finally,biological functions and metabolic pathways of key nodes were analyzed by DAVID database.Results:Totally 37 active components of Liuwei Dihuang pills were screened out,and 148 related targets were predicted according to the target prediction technique.The pathways involved in the key targets included the diabetic complication pathway,insulin resistance,inflammatory pathway and oxidative stress pathway.Conclusion:The studies based on network pharmacology showed that Liuwei Dihuang pills may interfere with diabetes through the diabetes complication pathway,insulin resistance,inflammatory pathway and oxidative stress pathway,which provides a reliable scientific basis for elucidating the pharmacological activity and action mechanism of the classic traditional Chinese medicine Liuwei Dihuang pills.