基于网络药理学和分子对接技术探究鸭跖草治疗高热惊厥的作用机制

Mechanism of Action of Commelina communis L.in the Treatment of Febrile Seizures Based on Network Pharmacology and Molecular Docking Technology

目的:基于网络药理学和分子对接技术探究鸭跖草治疗高热惊厥的作用机制。方法:通过检索中药系统药理学(the Chinese Medicine System Pharmacology,TCMSP)数据库、BATMAN-TCM数据库提取鸭跖草的有效成分并提取相关作用靶点,通过GeneCards和OMIM数据库检索高热惊厥疾病靶点。运用Uniport将蛋白与基因symbol转换,通过Darw venn diagram平台得出venn图及药物成分与疾病的交集基因。通过STRING数据库构建PPI网络。利用Cytoscape3.9.1软件构建“中药-有效成分-靶点”网络及“关键靶点-信号通路”网络,采用在线分析平台DAVID v6.8对关键靶点进行京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路富集分析和基因本体(gene ontology,GO)富集分析。利用软件R x644.0.2及绘图包ggplot2绘制KEGG信号通路和GO富集分析图。利用AutoDockTools 1.5.7,Pymol 2.0.1和Openbable3.1.1软件完成分子对接。结果:鸭跖草主要有效成分8种,对应靶点140个,疾病靶点2210个,药物疾病共同靶点64个,GO富集分析得到262条目(P<0.05)、KEGG通路富集分析筛选出67条信号通路(P<0.05),分子对接的结果显示,鸭跖草的活性成分黄酮类化合物主要通过3QXY,1GFW和2K7W等靶点调节多条信号通路发挥抗高热惊厥作用。结论:鸭跖草中的黄酮、β-谷甾醇和丙二酸单酰基人参皂苷Rb2等成分可与高热惊厥疾病靶点稳定结合并且结合能力强于临床上用于治疗高热惊厥的苯巴比妥,鸭跖草可通过多成分、多靶点、多通路治疗高热惊厥,本研究为鸭跖草用于高热惊厥治疗的研究与开发提供了新的思路。

Objective:To explore the mechanism of Commelina communis L.in the treatment of febrile seizures based on network pharmacology and molecular docking technology.Methods:The effective components of Commelina communis L.and their related targets were extracted by searching the Chinese Medicine System Pharmacology(TCMSP)database and BATMAN-TCM database.The disease targets of febrile seizures were searched through GeneCards and OMIM databases.Uniport was used to convert protein and gene symbols,and Darw venn diagram platform was used to obtain venn diagram and intersection genes between drug components and diseases.A PPI network was built through the STRING database.Cytoscape3.9.1 software was used to construct the“traditional Chinese medicine-active ingredients-target”network and“key target-signaling pathway”network.The online analysis platform DAVID v6.8 was used to perform KEGG signaling pathway enrichment analysis and GO enrichment analysis of the key targets.The software R x644.0.2 and the drawing package ggplot2 were used to plot the KEGG signal path and GO enrichment analysis diagram.Molecular docking was done using AutoDockTools 1.5.7,Pymol 2.0.1 and Openbable 3.1.1 software.Results:There were 8 main effective components of Commelina communis L.,which correspond to 140 targets,2210 disease targets and 64 common targets of drug diseases.262 items were obtained by GO enrichment analysis(P<0.05),and 67 signaling pathways were selected by KEGG enrichment analysis(P<0.05).The results of molecular coupling showed that flavonoids,the main component of Commelina communis L.,mainly regulating multiple signaling pathways through 3QXY,1GFW,2K7w and other targets to play a therapeutic role in the treatment of febrile seizures.Our research provided references and basis for the follow-up research.Conclusion:The flavonoids,β-sitosterol and monoacyl ginsenoside Rb2 in Commelina communis L.can stably bind to the target of febrile seizure disease and have stronger binding ability than phenobarbital,which is used for febrile seizures in clinical,and can treat febrile seizures through multi-component,multi-target,and multi-pathway.It provides new ideas for the research and development of Commelina communis L.and treatment options for hyperthermic seizures.