基于网络药理学研究消化复宁汤治疗浅表性胃炎胃脘痛的作用机制

Mechanism of Xiaohua Funing Decoction in the treatment of epigastric pain in chronic superficial gastritis based on network pharmacology

目的:利用网络药理学方法及分子对接技术探究消化复宁汤治疗浅表性胃炎(CSG)胃脘痛的作用机制。方法:通过中药系统药理学数据库(TCMSP)、中医药百科全书数据库(ETCM)、本草图鉴数据库(HERB)搜索消化复宁汤组成药物的有效成分及靶点,在GeneCards、DisGeNET、OMIM数据库搜索CSG的基因靶点,进而获得药物-疾病交集靶点;将交集靶点导入STRING蛋白质互作分析数据库和Cytoscape 3.9.1绘图软件,构建PPI网络图,并筛选核心靶点;再将核心靶点导入DAVID数据库,对其分别进行GO功能富集分析和KEGG通路富集分析;最后选择消化复宁汤的有效成分与核心靶点用AutoDockTool 1.5.6与PyMOL 2.5.0软件进行分子对接及可视化。结果:检索到消化复宁汤药物活性成分118个,靶点基因305个,浅表性胃炎疾病靶点973个,交集靶点118个;筛选出核心靶点21个,分别为IL-1β、ALB、IL-6、Akt1、TNF等。GO功能富集分析结果表明,消化复宁汤治疗CSG主要涉及炎症、药物反应,细胞生长凋亡等;KEGG通路富集程度相对较高的通路有癌症与糖尿病并发症通路、MAPK信号通路、IL-17信号通路、PI3K-Akt信号通路等。分子对接结果显示,核心作用靶点与有效成分具有较稳定的结合能力。结论:消化复宁汤中各种药物成分通过多靶点、多通路协同治疗CSG,为进一步研究CSG胃脘痛治疗提供了线索。

Objective:To explore the mechanism of Xiaohua Funing Decoction in the treatment of epigastric pain in chronic superficial gastritis(CSG)by network pharmacology and molecular docking technology.Methods:The active ingredients and targets of Xiaohua Funing Decoction were searched through Traditional Chinese Medicine Systems Pharmacology database(TCMSP),the Encyclopedia of Traditional Chinese Medicine(ETCM)and the Herb database(HERB).The gene targets of CSG were searched in GeneCards,DisGeNET and OMIM databases,and the drug-disease intersection targets were obtained.The intersection targets were imported into the STRING protein interaction analysis database and Cytoscape 3.9.1 mapping software to construct the PPI network and screen the core targets.Then,the core targets were imported into the DAVID database for GO functional enrichment analysis and KEGG pathway enrichment analysis.Finally,the active ingredients and core targets of Xiaohua Funing Decoction were selected for molecular docking and visualization by using AutoDock Tool 1.5.6 and PyMOL 2.5.0 software.Results:A total of 118 active ingredients of Xiaohua Funing Decoction,305 target genes,973 disease targets of CSG and 118 intersection targets were retrieved.21 core targets were screened,including IL-1β,ALB,IL-6,Akt1,TNF,etc.GO functional enrichment analysis showed that the treatment of CSG with Xiaohua Funing Decoction mainly involved inflammation,drug reaction,cell growth and apoptosis.KEGG pathway enrichment degree was relatively high with cancer and diabetes complications pathway,MAPK signal pathway,IL-17 signaling pathway,PI3K-Akt signaling pathway,etc.Molecular docking results showed that the core target had a stable binding ability with the active ingredients.Conclusion:Various drug components in Xiaohua Funing Decoction can treat CSG through multi-target and multi-pathway synergism,which provides clues for further study of the treatment of epigastric pain in CSG.