基于系统药理学的葛根芩连汤治疗2型糖尿病作用机制探讨

目的:通过系统药理学方法探讨葛根芩连汤治疗2型糖尿病的作用机制及原理。方法:利用中药系统药理学分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)数据库筛选葛根芩连汤有效成分和相关靶标蛋白;运用网络可视化软件Cytoscape 3.5.1构建葛根芩连汤"有效成分-靶标"相互作用网络进行拓扑学分析;借助STRING 10.5在线数据库进行蛋白质与蛋白质相互作用(protein-protein interaction networks,PPI)网络的构建与分析;通过Uniprot数据库获取靶标蛋白的基因名称,借助David数据库进行基因通路功能富集分析京都基因和基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG),研究葛根芩连汤治疗2型糖尿病的作用机制及原理。结果:葛根芩连汤的核心化合物有槲皮素(quercetin),山柰酚(kaempferol),β-谷甾醇(beta-sitosteroll)等,核心靶标前列腺素G/H合成酶2(prostaglandin G/H synthase 2)等;PPI网络图显示葛根芩连汤有效成分中关键蛋白主要有c-Jun氨基末端激酶(JUN),肿瘤坏死因子(TNF),fos蛋白(FOS),丝裂原活化蛋白激酶3(MAPK3)等;KEGG结果表明葛根芩连汤主要作用与肿瘤坏死因子信号通路(TNF signaling pathway),丝裂原活化蛋白激酶信号通路(MAPK signaling pathway)等信号通路有关。结论:葛根芩连汤主要通过多种途径,多种信号通路作用于多种靶点发挥其药物功效,起到抗炎功效,治疗2型糖尿病的作用。

Therapeutic Mechanism of Gegen Qinlian Tang Based on Systematic Pharmacology in Treatment of Type 2 Diabetes

Objective: To explore the mechanism and principle of Gegen Qinlian Tang in the treatment of type 2 diabetes by systematic pharmacology. Method: The effective components and related target proteins in Gegen Qinlian Tang were selected by using the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP); the network visualization software Cytoscape 3.5.1 was used to construct the effective component-target interaction network of Gegen Qinlian Tang for topological analysis. Protein and protein interaction network (PPI) was constructed and analyzed with STRING 10.5 online database. After the gene names of target proteins were obtained from Uniprot database, kyoto encyctopedia of genes and genomes(KEGG) pathway analysis was conducted by using David database to explore the mechanism and principle of Gegen Qinlian Tang in treating type 2 diabetes. Result: The results showed that the core compounds of Gegen Qinlian Tang included quercetin, kaempferol, beta-sitosteroll, Prostaglandin G/H synthase 2, etc.; PPI network diagram showed that the key proteins in the effective constituents of Gegen Qinlian Tang mainly included c-jun N-terminal kinase (JNK), tumor necrosis factor (TNF), fos protein (FOS), mitogen activated protein kinase 3 (MAPK3), etc. KEGG results showed that the main effect of Gegen Qinlian Tang was associated with TNF signaling pathway and MAPK signaling pathway signal pathway. Conclusion: Gegen Qinlian Tang mainly plays its anti-inflammatory effect, so as to achieve the effect of treating type 2 diabetes through multiple targets and multiple signaling pathways.