基于网络药理学及分子对接的补中益气汤“异病同治”慢性尿路感染、肾性血尿和肾性蛋白尿的作用机制

Mechanism of“Homotherapy of Different Diseases”by Buzhong Yiqi Decoction for Chronic Urinary Tract Infections,Renal Hematuria and Renal Albuminuria Based on Network Pharmacology and Molecular Docking

目的:探讨补中益气汤治疗慢性尿路感染(CUTI)、肾性血尿(RH)和肾性蛋白尿(RA)的“异病同治”作用机制。方法:获取补中益气汤与CUTI、RH及RA相关的共有靶点。利用Cytoscape软件设计药物-活性成分-交集靶点网络图。将共有靶点导入STRING数据库进行蛋白质-蛋白质相互作用分析,筛选出核心靶点。利用DAVID数据库对交集靶点进行基因本体功能富集分析和京都基因与基因组百科全书通路富集分析。使用AutoDock软件将主要的活性成分与核心靶点进行分子对接验证。结果:补中益气汤治疗3种疾病涉及复方中黄酮类、植物甾醇类、苷类及五环三萜类等多种化合物,其治疗机制可能通过参与调节癌症途径、磷脂酰肌醇3激酶-蛋白激酶B信号通路、丝裂原激活的蛋白激酶信号通路、肾素-血管紧张素系统信号通路、Rap1信号通路和缺氧诱导因子-1信号通路等调节细胞凋亡和免疫炎症等,因此达到对3种疾病“异病同治”的作用。分子对接结果显示,主要活性成分分别与核心靶点结合且拥有较稳定的分子构象。结论:补中益气汤通过多成分、多靶点、多通路之间相互联系对应,以达到“异病同治”CUTI、RH及RA的作用。

OBJECTIVE:To probe into the mechanism of Buzhong Yiqi decoction in the treatment of chronic urinary tract infection(CUTI),renal hematuria(RH)and renal proteinuria(RA).METHODS:Common targets of Buzhong Yiqi decoction related to CUTI,RH and RA were obtained.Drug-active component-intersection target network diagram was designed by using Cytoscape software.Common targets were imported into STRING database for protein-protein interaction analysis,and core targets were screened out.Gene Ontology function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes Pathway enrichment analysis were performed for intersection targets by using DAVID database.Molecular docking of major active components to core targets was performed by using AutoDock software.RESULTS:The treatment of three kinds of diseases by Buzhong Yiqi decoction involved in a variety of compounds such as flavonoids,phytosterols,glycosides and pentacyclic triterpenoids,its therapeutic mechanism may be involved in the regulation of cancer pathway,phosphatidylinositol 3 kinase-protein kinase B signaling pathway,mitogen activated protein kinase signaling pathway,Ras signaling pathway,Rap1 signaling pathway and hypoxia-inducible factor-1 signaling pathway to regulate cell apoptosis and immune inflammation,so as to achieve the role of homotherapy of three kinds of diseases.Results of molecular docking showed that the main active components were bound to the core target respectively and had relatively stable molecular conformation.CONCLUSIONS:By linking multiple-components,multiple-targets and multiple-pathways,Buzhong Yiqi decoction can achieve the therapeutic effect of CUTI,RH and RA by“homotherapy of different diseases”.