摘要
目的通过网络药理学和分子对接技术研究熊果酸抗颞叶癫痫的作用机制。方法利用PharmMapper、SwissTargetPrediction数据库检索熊果酸的作用靶点,筛选PharmMapper数据库中NormFit评分大于平均值的靶点和SwissTargetPrediction数据库中Probability大于0的靶点;以“temporal lobe epilepsy”为关键词,利用在线人类孟德尔遗传数据库(OMIM)和人类基因综合数据库(GeneCards),分别检索出颞叶癫痫相关靶点,取熊果酸作用靶点与颞叶癫痫相关靶点交集,获得熊果酸和颞叶癫痫的共同靶点并绘制韦恩图。通过基因本体论(GO)、京都基因与基因组数据库(KEGG)功能富集分析熊果酸在颞叶癫痫中可能作用的信号通路;结合STRING数据库,绘制靶点蛋白质-蛋白质相互作用(PPI)网络,结合Cytoscape软件筛选出熊果酸在颞叶癫痫中的潜在核心作用靶点,利用分子对接技术验证熊果酸与潜在核心作用靶点的亲和力。结果筛选得出熊果酸的作用靶点有175个,颞叶癫痫相关靶点有4609个,熊果酸和颞叶癫痫的共同靶点有85个。富集通路结果显示:熊果酸抗颞叶癫痫可能是通过雌激素信号通路、MAPK信号通路、PI3K-AKT信号通路等发挥作用的;熊果酸抗颞叶癫痫的潜在核心靶点为白蛋白(ALB)、表皮生长因子受体(EGFR)、雌激素受体1(ESR1)。分子对接结果显示:熊果酸与筛选得到的核心靶点均有很高的结合活性。结论熊果酸可能通过多靶点、多通路抗颞叶癫痫。
Objective To study the mechanisin ursolic acid in temporal lobe epilepsy by network pharmacology and molecular docking techniques.Methods We used PharmMapper and SwissTargetPrediction databases to search for ursolic acid targets and screened out targets with NormFit scores greater than average in PharmMapper and Probability greater than 0 in SwissTargetPrediction.The“temporal lobe epilepsy”related targets were searched in the Online Mendelian Inheritance in Man(OMIM)and GeneCards databases.We took the intersection of the targets of ursolic acid and temporal lobe epilepsy-related targets to obtain the common targets of ursolic acid and temporal lobe epilepsy and draw a Venny.Next,we used GO and KEGG functional enrichment analysis to identify the signaling pathways on which ursolic acid may effect in temporal lobe epilepsy.Finally,we imported the data of the common targets into the STRING database to draw a protein-protein interaction(PPI)network of targets,and Cytoscape software was used to screen the potential core targets of ursolic acid in temporal lobe epilepsy.Tthe affinity between ursolic acid and the potential core targets was verified by molecular docking.Results The results showed that there were 175 targets of ursolic acid,4609 temporal lobe epilepsy-related targets,and 85 common targets of ursolic acid and temporal lobe epilepsy.The enrichment pathway analysis showed that the effect mechanism of ursolic acid on temporal lobe epilepsy may relate with estrogen signaling pathway,MAPK signaling pathway,PI3K-AKT signaling pathway,etc.The potential core targets of ursolic acid against temporal lobe epilepsy were screened out,which are albumin(ALB),epidermal growth factor receptor(EGFR)and estrogen receptor 1(ESR1).The molecular docking results showed that ursolic acid had high binding activity with the screened core targets.Conclusion Ursolic acid may inhibit temporal lobe epilepsy through various targets and pathways.
作者
贺勇弘
李娟娟
王雅禾
杨勇
刘昆梅
HE Yonghong;LI Juanjuan;WANG Yahe;YANG Yong;LIU Kunmei(Key Laboratory of Craniocerebral Diseases,Ningxia Medical University,Yinchuan 750004,China;General Hospital of Ningxia Medical University,The First Clinical Medical College of Ningxia Medical University,Yinchuan 750004,China)
出处
《宁夏医科大学学报》
2024年第10期1052-1058,共7页
Journal of Ningxia Medical University
基金
国家自然科学基金项目(82360711
32070930)
宁夏自然科学基金项目(2023AAC03155)
宁夏颅脑疾病重点实验室主任基金项目(LNZR202304)
宁夏回族自治区青年拔尖人才项目
宁夏回族自治区校级大学生创新创业训练计划项目(X202210752042)。
关键词
熊果酸
颞叶癫痫
网络药理学
分子对接
ursolic acid
temporal lobe epilepsy
network pharmacology
molecular docking techniques
