基于网络药理学与分子对接技术探讨麻子仁丸治疗功能性便秘的作用机制

The Mechanism of Maziren Pill in the Treatment of Functional Constipation Based on Network Pharmacology and Molecular Docking Technology

目的:通过网络药理学和分子对接方法探讨麻子仁丸治疗功能性便秘的作用机制。方法:在TCMSP数据库中检索麻子仁丸中各药物的主要活性成分及作用靶点,并应用UniProt数据库筛选功能性便秘的相关疾病靶点。应用Cytoscape 3.7.2软件构建有效活性成分-靶点网络;用STRING数据库构建PPI网络,基于Bioconductor数据库利用R 3.6.3软件进行基因本体论(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析,并提取前20条结果生成可视化图形。结果:获取麻子仁丸的主要活性成分57个;作用靶点167个,功能性便秘相关基因4948个,交集基因135个。较重要的有效活性成分包括木犀草素、山柰酚、柚皮素等。构建可视化PPI网络图共得到135个节点、2033条边、平均度值30.1,获得AKT1、IL-6、MAPK3等30个核心靶点蛋白。GO富集分析获得条目154个,其中10个富集最多,KEGG通路富集分析获得175条信号传导通路,其中16条富集显著性较高。结论:麻子仁丸可能是通过AGE-RAGE、TNF、IL-17、PI3K-Akt等信号通路控制AKT1、IL-6、MAPK3等靶点治疗功能性便秘,木犀草素可能发挥重要作用。

Objective:To survey the mechanism of Maziren pill in the treatment of functional constipation(FC)by network pharmacology and molecular docking technology.Methods:The main active ingredients and targets of the herbs in Maziren pills were searched from TCMSP database,and the related disease targets of FC were screened using UniProt database.The effective active ingredients-targets network was constructed using Cytoscape 3.7.2 software;PPI network was built using STRING database,GO and KEGG enrichment analysis were performed using R3.6.3 software on the foundation of Bioconductor database,and the first 20 results were extracted to generate visual graphs.Results:All 57 main active ingredients of Maziren pills were obtained;involving 167 targets,4948 related genes of FC and 135 intersected genes.More important effective active ingredients contained luteolin,Kaempferol and naringenin.The construction of visualization PPI network has obtained 135 nodes,2033 edges and average degree value 30.1,covering 30 key target proteins such as AKT1,IL-6 and MAPK3.There were 154 items obtained in GO enrichment analysis,and ten items were enriched the most,175 signal transduction pathways were yielded in KEGG pathway,and 16 pathways presented higher significance in enrichment.Conclusion:Maziren pill could treat FC possibly through controlling AKT1,IL-6 and MAPK3 via AGE-RAGE,TNF,IL-17 and PI3K-Akt signal pathways,among which,luteolin might play the important role.