黄芪-生地-地骨皮药串防治2型糖尿病的网络药理学分析

Analyzing String of Astragali Radix-Rehmanniae Radix-Lycii Cortex for Treatment of Type 2 Diabetes Mellitus Based on Network Pharmacology

目的运用网络药理学方法探讨黄芪-生地-地骨皮药串防治2型糖尿病(Type 2 diabetes mellitus,T2DM)的潜在效应机制。方法利用TCMSP数据库和BATMAN-TCM数据库收集黄芪-生地-地骨皮药串的活性成分及其作用靶点,采用Cytoscape软件构建药串-活性成分-靶点网络。通过GeneCards、DisGeNET数据库获取并筛选T2DM疾病相关靶点。运用STRING数据库构建药串-T2DM靶蛋白互作(PPI)网络,筛选药串治疗T2DM的关键靶点。通过ClueGo和MCODE插件对关键靶点进行GO聚类分析与KEGG通路富集分析,利用Bioinformatics工具对结果进行可视化处理,并基于GeneCards数据库分析靶点和通路的相关性。结果共获得黄芪-生地-地骨皮药串的29种有效成分及其675个作用靶点;获得T2DM疾病靶点303个。PPI分析得到黄芪-生地-地骨皮药串治疗T2DM的关键靶点64个,包括INS、PPARG、CRP、PTGS2等;主要涉及调节胰岛素抵抗、胰岛素信号通路、PI3K-Akt、Toll样受体信号通路、TNF信号通路和细胞凋亡等生物过程及通路。结论黄芪-生地-地骨皮药串主要通过缓解胰岛素抵抗、抗凋亡和抗炎等发挥防治2型糖尿病的作用。

Objective To investigate the mechanism of Astragali radix-Rehmanniae radix-Lycii cortex for treatment of type 2 diabetes mellitus based on network pharmacology.Methods Based on the BATMAN-TCM and TCMSP,the components and targets of Astragali radix-Rehmanniae radix-Lycii cortex were obtained.The targets of type 2 diabetes mellitus were obtained from GeneCards and DisGeNET.The compositions-targets network and proteinprotein interactions(PPI)network were constructed using the Cytoscape software.The key components of the network and the key targets of the PPI network were obtained by network analyzer.KEGG pathways and GO of key targets were analyzed by means of ClueGo.Results The predicted results showed that there were 29 effective chemical constituents and 64 key targets of string acting on type 2 diabetes mellitus.The key active chemical compositions include Isoflavanone,Rehmannioside A,gamma-aminobutyric acid,etc.The key targets include INS,PPARG,CRP,PTGS2,and so on.Signaling pathways including Insulin resistance,PI3 K-Akt signaling pathway,Toll-like signaling pathway,TNF signaling pathway,cell apoptosis pathway,were identified by pathway enrichment analysis.Conclusion String of Astragali radix-Rehmanniae radix-Lycii cortex can relieve insulin resistance,anti-apoptosis and anti-inflammatory to exert a role in the treatment of type 2 diabetes mellitus.