基于网络药理学的苦参-地榆治疗溃疡性结肠炎、肛门湿疹的“异病同治”机制分析

Exploration on mechanisms of “treating different diseases with same method” of Sophora flavescens and Sanguisorba in treating ulcerative colitis and anal eczema based on network pharmacology

目的:预测苦参-地榆药对治疗溃疡性结肠炎(UC)和肛门湿疹“异病同治”的作用机制。方法:采用网络药理学方法,基于中药系统药理学分析平台(TCMSP)及检索相关文献,寻找苦参-地榆药对中活性成分及作用靶点,并以口服利用度(OB)≥30%,类药性(DL)≥0.18为条件进行筛选;利用OMIM、TTD、Drug Bank数据库检索UC和肛门湿疹疾病相关靶点;通过R语言将苦参-地榆药对与UC和肛门湿疹靶点做Venn图;采用Cytoscape软件绘制疾病-药对-成分-靶点网络;利用STRING数据库,构建蛋白互作网络模型(PPI),并通过Cytoscape软件进行优化;基于Matescape数据平台,对药对治疗UC和肛门湿疹的共同靶点进行基因本体(GO)生物功能和基因组百科全书(KEGG)通路富集分析。结果:筛选后得出,苦参-地榆药对活性成分57个、靶点179个,UC靶点561个,肛门湿疹靶点677个,药对与两疾病交集靶点49个,包括IL-6、JUN、TNF、AKT1等。GO生物过程分析主要涉及对脂多糖的反应、对有毒物质的反应、对活性氧的反应等生物过程;KEGG富集分析共得到15条信号通路,主要包括IL-17信号通路、癌症通路、细胞因子受体相互作用等。结论:苦参-地榆药对“异病同治”UC和肛门湿疹是通过其多成分、多靶点、多通路的特点实现的,为进一步临床拓展应用及实验验证提供参考依据。

Objective:To predict the mechanism of Sophora flavescens and Sanguisorba officinalis in treating ulcerative colitis(UC)and Anal eczema.Methods:Network pharmacology was used.Based on TCMSP and searching related literatures,we searched for active components and targets in drug pairs,and screened them with oral bioavailability(OB)≥30%and drug-likeness(DL)≥0.18;searched UC and Anal eczema related targets with OMIM,TTD and DrugBank databases;Venn diagrams were made between the drug pairs and the targets of UC and anal eczema by R language;The network diagram of"drug-component-target-disease"is constructed by using Cytopscape software;Using string database,protein-protein interaction network model(PPI)was constructed,and optimized by Cytoscape software,and the network diagram of"drug-disease"core target is constructed by using the software of cytopscape.Based on the data platform of matescape,Gene Ontology(GO)biological function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of the common targets of drug pair in the treatment of UC and anal eczema were carried out.Results:after screening,there were 57 active components and 179 targets of drug pair,561 UC targets,677 anal eczema targets and 49 intersection targets,including IL6,Jun,TNF and AKT1.Go biological process analysis mainly involved response to lipopolysaccharide,response to toxic substance,response to reactive oxygen species and other biological processes;KEGG enrichment analysis obtained 15 signaling pathways,including IL-17 signaling pathway,cancer pathway,cytokine receptor interaction and so on.Conclusion:Sophora flavescens and Sanguisorba officinalis can treat UC and Anal eczema through its multi-component,multi-target and multi-channel characteristics,which can provide reference for further clinical application and experimental verification.