基于网络药理学和分子对接探讨癫痫宁片治疗癫痫的潜在作用机制研究

Mechanism exploring of Dianxianning Tablets in treatment of epilepsy based on network pharmacology and molecular docking technology

目的通过网络药理学和分子对接方法,筛选癫痫宁片治疗癫痫的主要活性成分和分子机制。方法采用TCMSP、Herb数据库筛选癫痫宁片中的主要活性成分及靶点;GeneCard、OMIM、DisGent筛选癫痫的治疗靶点;使用Cytoscape 3.8.2软件构建“药物活性成分–靶点”网络;将药物–交集基因上传至相互作用数据库String构建蛋白相互作用(PPI)网络。将药物–疾病交集基因上传至利用生物信息学开源软件Bioconductor,对其进行生物学过程的基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析,并对关键靶点与成分进行分子对接验证。结果共筛选到癫痫宁片有效成分70个,靶点308个,其中degree前9位的活性成分分别为毛钩藤碱、山柰酚、狼尾草麦角碱、β-谷甾醇;核心靶点共10个,分别为V-Rel网状内皮增生病毒癌基因同源物A(RELA)、转录因子AP-1(JUN)、有丝分裂原活化蛋白激酶1(MAPK1)、信号传导和转录激活蛋白3(STAT3)、肿瘤蛋白p53(TP53)、蛋白激酶B1(Akt1)、雌激素受体α(ESR1)、肿瘤坏死因子(TNF)、有丝分裂原活化蛋白激酶8(MAPK8)。共筛选出5195个GO条目,富集到259条与药物治疗癫痫相关的通路。分子对接结果显示,核心靶点与活性成分间结合良好。结论基于网络药理学和分子对接方法对癫痫宁片治疗癫痫作用机制有了新的认识,阐明药物活性成分与癫痫的关系,为临床药物治疗提供了科学依据。

Objective To screen the main active ingredients and molecular mechanism of Dianxianning Tablets through network pharmacology and molecular docking methods.Method TCMSP and Herb database were used to screen the main active ingredients and targets of Dianxianning Tablets.GeneCard,OMIM,and DisGent were selected as therapeutic targets for epilepsy.Construct the“drug active ingredient-target”network using Cytoscape 3.8.2 software.The drug-intersection gene was uploaded to the interaction database String to construct the PPI network.The drug-disease intersection genes were uploaded to Bioconductor,the bioinformatics software was used to GO and KEGG pathways of biological processes,and the key targets and components were validated by molecular docking.Genetic Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed,and key targets and components were validated by molecular docking.Results A total of 70 active ingredients and 308 targets were selected for Dianxianning Tablets,in which the first 9 active ingredients of the degree were hirsutine,kaempferol,penniclavin,andβ-sitosterol,respectively.There are 10 core targets,including RELA,JUN,MAPK1,STAT3,TP53,Akt1,ESR1,TNF,MAPK8.A total of 5195 GO entries were screened,and 259 pathways related to drug treatment of epilepsy were enriched.The results of molecular docking showed that the core target was well bound to the active ingredient.Conclusion This study provided a new understanding of DianxianNing Tables’benefitting effect for treatment of epilepsy based on network pharmacology and molecular docking technology,which jointly elucidated the relationship between the active ingredients of drugs and epilepsy,and provi ded a scientific basis for clinical drug treatment.