基于网络药理学和分子对接探讨天麻素治疗癫痫的作用机制
Exploring the mechanism of action of gastrodin in treating epilepsy based on network pharmacology and molecular docking
魏雪莹 1姬亮亮 1杨冬花 1叶兰 2冯占辉3
作者信息
- 1. 550004,贵州贵阳,贵州省人民医院干部科
- 2. 550004,贵州贵阳,贵州医科大学基础医学院
- 3. 550004,贵州贵阳,贵州医科大学附属医院神经内科
- 折叠
摘要
目的 探讨基于网络药理学和分子对接研究天麻素抗癫痫治疗的靶点及机制.方法 在 PharmMapper、SwissTargetprediction、Drugband、TCMIP 检索出天麻素的作用靶点,在 OMIM、Gencard、Disgenet获取癫痫疾病靶点,使用Venny 2.1在线平台获取天麻素和癫痫的交集靶点.使用String数据库建立蛋白相互作用网络(PPI),采用Cytoscape 3.7.1软件筛选出关键靶点.用DA-VID数据库进行GO功能和KEGG通路富集分析,然后对关键成分进行分子对接验证.结果 共获取天麻素治疗癫痫靶点192个,筛选得到关键靶点14个,KEGG通路富集分析主要涉及PI3K/AKT/FOXO信号通路和MAPK信号通路.分子对接结果显示,IGF1、ALB、ESR1、AKT1、HSP90AA1、MAPK1、RHOA及MAPK14与天麻素分子有较好的结合能,其可能是天麻素治疗癫痫的核心靶点.结论 天麻素可通过多靶点、多途径治疗癫痫,其中IGF-1、HSP90AA1、HSP90AB1可能是天麻素治疗癫痫的关键上游靶基因,PI3K/AKT可能是关键作用通路,其机制可能与抑制炎症及调控细胞调亡相关分子有关联.
Abstract
Objective To investigate the targets of gastrodin in anti-epileptic therapy and its mechanisms based on network pharmacology and molecular docking.Methods The targets of gastrod-in were retrieved from PharmMapper,Swiss Targetprediction,Drugband and TCMIP,and the targets of epilepsy were obtained from OMIM,Gencard and Disgene.Venny2.1 online platform was applied to obtain the intersection targets between gastrodin and epilepsy.A protein-protein interaction network(PPI)was constructed using a String database,and key targets were screened using Cytoscape 3.7.1 software.DAVID database was performed to analyze GO function annotation and KEGG pathway en-richment.Molecular docking was conducted on key components.Results A total of 192 targets for treating epilepsy with gastrodin were obtained,and 14 key targets were identified through screening.KEGG pathway enrichment analysis revealed that mainly involved pathways were PI3K/AKT/FOXO and MAPK signaling pathways.Molecular docking results showed that IGF1,ALB,ESRI,AKT1,HSP90AA1,MAPK1,RHOA and MAPK14 had good binding energy between molecules and pro-teins,and they might be the core targets of gastrodin in treating epilepsy.Conclusion Gastrodin can treat epilepsy through multiple targets and pathways,among which,IGF-1,HSP90AA1 and HSP90AB1 may be key upstream target genes of gastrodin in treating epilepsy.PI3K/AKT may be a key pathway,and its mechanism may be related to inhibiting inflammation and regulating cell apopto-sis-related molecules.
关键词
天麻素/癫痫/网络药理学/分子对接/IGF-1/HSP90AA1/HSP90AB1Key words
gastrodin/epilepsy/network pharmacology/molecular docking/IGF-1/HSP90AA1/HSP90AB1引用本文复制引用
基金项目
国家自然科学基金项目(81960224)
国家自然科学基金项目(82360266)
贵州省卫生健康委科学技术基金项目(gzwkj2024-302)
贵州省科技厅项目(黔科合基础-ZK[2023]一般395)
贵州省科技厅项目(324)
出版年
2024
NETL
NSTL
万方数据