基于数据挖掘和网络药理学探讨国家专利中药复方治疗肛周湿疹的用药规律及作用机制

Exploring medication rules and action mechanism of the national patents TCM compound on perianal eczema based on data mining and network pharmacology

目的:运用数据挖掘和网络药理学分析国家专利中药复方治疗肛周湿疹的用药规律,并探讨核心药物治疗肛周湿疹的作用机制。方法:检索国家知识产权局专利库中治疗肛周湿疹的中药复方专利,通过中医传承计算平台V3.0进行频次统计、关联规则、聚类分析等。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)对核心药物进行活性成分、靶点筛选,使用Cytoscape 3.7.1软件构建“药物-活性成分-靶点”网络图;在Gene Cards、OMIM数据库检索肛周湿疹靶点,运用STRING数据库构建蛋白质-蛋白质相互作用网络图;运用DAVID数据库进行基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。通过Autodock Vina对活性成分和关键靶点进行分子对接验证。结果:纳入中药复方专利67项,涉及中药297味,药物性味以苦、寒为主,药物归经主要为肝经、脾经、肾经等;核心药物有苦参、黄柏、蛇床子、地肤子、白鲜皮等。通过TCMSP数据库筛选出69个药物活性成分和190个靶点,核心靶点有白细胞介素6(Interleukin-6,IL6)、基质金属蛋白酶9(Matrix Metalloproteinase 9,MMP9)、趋化性细胞因子8(Chemokine 8,CXCL8)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、肿瘤抑制p53蛋白(Tumor Protein P53,TP53)等,GO富集分析得到生物过程129个,细胞组分10个,分子功能15个,KEGG富集分析得到48条信号通路。分子对接结果显示与关键靶点对接较好的活性成分有槲皮素、木犀草素、汉黄芩素。结论:临床治疗肛周湿疹应以清热利湿、杀虫祛风止痒为基本治则;核心药物治疗肛周湿疹具有多成分、多靶点、多通路等特点,为进一步的基础实验研究和中药新药开发奠定了基础。

Objective:To analyze medication rules of the national patents traditional Chinese medicine compound on perianal eczema based on data mining and network pharmacology,and to explore the action mechanism of the core medicines on perianal eczema.Methods:The national patents of traditional Chinese medicine compound on perianal eczema in the State Intellectual Property Office Patent Database were searched.The frequency statistics,association rules,and cluster analysis were performed through traditional Chinese medicine inheritance computer system V3.0.The active ingredients and targets of core medicines were screened by TCMSP database.A“medicine-active ingredient-target”network diagram was constructed by Cytoscape 3.7.1 software.The targets of perianal eczema were searched in GeneCards and OMIM databases.A PPI network diagram was constructed by STRING database.The GO function enrichment analysis and KEGG pathway enrichment analysis was perfromed through DAVID database.The molecular docking of active ingredients and key targets was verified by Autodock Vina.Results:67 national patents traditional Chinese medicine compound were included,involving 297traditional Chinese medicines.The main medicinal properties were bitter and cold.The active ingredients of traditional Chinese medicines mainly flowed into liver meridian,spleen meridian,kidney meridian,etc..The core medicines included Kushen(Sophora flavescens),Huangbo(Phellodendron amurense),Shechuangzi(Cnidium monnieri),Difuzi(Kochia scoparia seed),and Baixianpi(White fresh peel),etc..69 active pharmaceutical ingredients and 190 targets were screened through TCMSP database.The core targets were IL6,MMP9,CXCL8,TNF,TP53,etc..The GO enrichment analysis revealed 129 biological processes,10 cellular components,and 15 molecular functions.The KEGG enrichment analysis obtained 48 signal pathways.The molecular docking results showed that the active ingredients that docked well with key targets were quercetin,luteolin,and wogonin.Conclusion:The basic treatment principles of perianal eczema should be to clear way heat,remove dampness,kill insects,dispel wind and relieve itching.The core medicines on perianal eczema has the characteristics of multiple components,multiple targets,multiple pathways,etc.,which lays the foundation for further basic experimental research and the development of new traditional Chinese medicines.