基于网络药理学探究麻子仁丸治疗功能性便秘的作用机制

An exploration on mechanisms of MaZiRen pill in Treating Functional Constipation based on network pharmacology

目的运用网络药理学方法预测麻子仁丸治疗功能性便秘(FC)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,寻找麻子仁丸中各药物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、Therapeutic Target Database(TTD)、DrugBank数据库检索功能性便秘相关靶点;通过R语言将麻子仁丸与功能性便秘潜在靶点做Venn图;采用Cytoscape软件绘制药物-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,对潜在靶点进行基因本体(GO)生物功能和基因组百科全书(KEGG)通路富集分析。结果筛选后得出活性成分49个、靶点175个,功能性便秘靶点622个,麻子仁丸治疗功能性便秘靶点49个,包括白介素-6(IL-6)、蛋白激酶1(AKT1)、血管内皮生长因子-A(VEGFA)、肿瘤坏死因子(TNF)等。KEGG富集分析共得到238条信号通路,主要包括癌症通路、丙型肝炎、膀胱癌、IL-17信号通路及麻疹等。结论麻子仁丸治疗功能性便秘是通过其多成分、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 MaZiRen pill in the treatment of functional constipation(FC)by network pharmacology.Methods Use the methods of network pharmacology.The effective chemical constituents and targets of MaZiRen pill and the disease targets of FC were searched by TCMSP,OMIM,Therapeutic Target Database(TTD),DrugBankand and related literatures,were screened with OB≥30%and DL≥0.18;Venn map of potential targets of MaZiRen pill and FC was made by R language;The interaction network of“drugs-effective chemical composition-target”was constructed by Cytoscape software;The interaction network of potential target proteins was constructed by STRING database and the potential targets were annotated by Uniprot database.Matescape database was used to analyze GO biological function and KEGG pathway enrichment of potential targets.Results A total of 49 effective chemical constituents,175 targets,622 targets for FC,and 49 potential targets for the therapeutic effect were obtained,including IL-6,PTK-1,VEGFA,TNF,etc.GO biological function and KEGG pathway enrichment analysis showed that a total of 238 pathways were involved in potential targets,including cancer pathway,hepatitis C,bladder cancer,IL-17 signaling pathway and measles.Conclusion MaZiRen pill in the treatment of FC is achieved by its multi-component,multi-target and multi-channel characteristics,which provides reference for further clinical application and experimental verification.