基于数据挖掘和网络药理学分析中药熏洗方治疗肛周湿疹的用药规律及机制

The Medication Rules and the Mechanism of Herbal Fumigation Formulation in the Treatment of Perianal Eczema Based on Data Mining and Network Pharmacology

目的:应用数据挖掘和网络药理学方法探讨中药熏洗方治疗肛周湿疹的用药规律及机制。方法:检索中国知网、万方、维普、中国生物医学文献数据库2011年1月1日至2020年12月31日关于中药熏洗治疗肛周湿疹的文献;采用中医传承辅助平台V3.0软件对处方用药频次、药性、药味、归经、组方规律、药物核心组合进行分析。通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)检索用药规律所得苦参汤中8味药物的活性成分及其对应的药物靶点;运用人类基因数据库(the human gene database,GeneCards)获取肛周湿疹的疾病靶点;使用Venny 2.1.0作图工具映射药物与疾病交集靶点,并构建韦恩图;运用STRING数据库及Cytoscape 3.8.2软件构建靶点蛋白-蛋白互作网络(protein-protein interactions,PPI),筛选核心作用靶点,构建“药物-活性成分-作用靶点”网络;应用R语言的clusterProfiler包进行基因本体论(gene ontology,GO)及京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。结果:共筛选出符合标准的文献386篇,纳入中药处方360首,涉及中药188味;用药频次≥10次的药物共51味,四气分类以寒性为主,五味分类以苦味及辛味为主,药物归经以肝经、胃经及脾经为主;组方规律分析得到高频药对30对,最终演化得到核心组合4个,从用药规律得出苦参汤是治疗肛周湿疹的特效方。共筛选出苦参汤中137个活性成分和224个潜在靶点,与肛周湿疹相关作用靶点24个,经拓扑分析得到3个核心治疗靶点;筛选出槲皮素、木犀草素、山柰酚、金合欢素、苦参碱5个有效活性成分;GO富集分析得到1354个生物学过程、34个细胞组成及71个分子功能;KEGG通路富集分析得到97条信号通路。结论:苦参汤是治疗肛周湿疹的中药古方,苦参汤通过多成分、多靶点、多通路发挥治疗肛周湿疹的作用。

Objective:To survey the medication rules and the mechanism of herbal fumigation formulation in the treatment of perianal eczema based on data mining and network pharmacology.Methods:The literature on treating perianal eczema with herbal fumigation formulation was searched from CNKI,Wanfang,VIP and SinoMed between January 1,2011 and December 31,2020;traditional Chinese Medicine Inheritance Support System(TCMISS)V3.0 software was used to analyze the frequency of drug administration,the nature of the drugs,the flavor,meridian entropism,law of the prescription and core drug combination of the prescription.The active ingredients of eight kinds of herbs contained in Kushen decoction and the corresponding herbal targets were retrieved via TCMSP;disease targets of perianal eczema were obtained using the human gene database(GeneCards);Venny 2.1.0 mapping tool was used to map drug-disease intersection targets and construct Venny diagram;STRING database and Cytoscape 3.8.2 software were applied to construct protein-protein interactions(PPI)and screen the core targets,and construct the network of"medicine-active ingredients-targets of action";clusterProfiler package of R lanuage was used to carry out GO and KEGG pathway enrichment analysis.Results:The study screened out 386 articles which met the inclusion criteria,included 360 pieces of herbal prescriptions,and involved 188 herbs;there were 51 herbs with the frequency greater than ten times,mainly of cold nature,of bitter and pungent flavor,entering the meridians of liver,stomach and spleen;the analysis of drug administration yielded 30 high-frequency drug pairs,and the final evolution obtained four core combinations,and it was concluded that Kushen decoction was the effective prescription for the treatment of perianal eczema from the law of drug administration.All 137 active ingredients,224 potential targets and 24 targets related to perianal eczema were screened from Kushen decoction,three core therapeutic targets were obained via topological analysis;five effective active ingredients were obtained,including quercetin,lignocerotoxin,kaempferol,acacia-acacacia and picloram;GO enrichment analysis obtained 1354 biological processes,34 cellular components and 71 molecular functions;and KEGG pathway enrichment analysis received 97 signaling pathways.Conclusion:Kushen decoction as the ancient prescription for the treatment of perianal eczema,could play therapeutic roles in the treatment via multi-ingredient,multi-target and multi-pathway.