基于网络药理学的草果知母汤治疗癫痫的机制研究  

Mechanism of Caoguo Zhimu Decoction treating epilepsy based on the network pharmacology

作　　者：黄羚[1] 刘铁钢[1] 马雪颜 白辰[1] 徐竞男 刘邵阳[1] 于河[1] 谷晓红[1] Huang Ling;Liu Tiegang;Ma Xueyan;Bai Chen;Xu Jingnan;Liu Shaoyang;Yu He;Gu Xiaohong(Bejjing University of Chinese Medicine,Bejig 100029)

机构地区：[1]北京中医药大学,北京100029

出　　处：《现代中医临床》2020年第5期31-38,共8页Modern Chinese Clinical Medicine

基　　金：国家重点研发计划(No.2018YFC1704100);国家自然科学基金面上项目(No.81874421);北京中医药大学2020年基本科研业务费项目(No.2020-JYB-ZDGG-005)。

摘　　要：目的基于网络药理学探讨草果知母汤治疗癫痫的活性成分、作用靶点和作用机制。方法采用中药系统药理学数据库和分析平台和毒性与基因比较数据库获取活性成分并垂钓靶标,与中医药整合药理学研究平台v1.0的数据进行整合,得到最终的草果知母汤治疗癫痫靶标。采用全球蛋白质资源数据库进行蛋白基因互译,在相互作用基因/蛋白质的检索工具网站进行基因本体生物过程富集分析和信号通路富集分析,构建"中药-活性成分-核心靶标-关键通路"多层次网络图和各靶标间相互作用关系网络图。结果得到草果知母汤的活性成分75个和草果知母汤治疗癫痫靶标89个,其作用机制涉及钠离子通道蛋白1亚单位α、钠离子通道蛋白2亚单位α、钠离子通道蛋白8亚单位α、RAC-α-丝氨酸/苏氨酸蛋白激酶、γ-氨基丁酸受体亚单位β-2、γ-氨基丁酸受体亚单位β-3、γ-氨基丁酸受体亚单位δ等多个关键靶点以及神经活性配体-受体相互作用、各种神经突触通路、钙信号通路、雌激素信号通路、细胞衰老、药物及烟酒成瘾等多条通路发挥抗癫痫的作用。结论草果知母汤治疗癫痫的作用机制是多途径、多靶点的。Objective To explore the active components,targets and mechanism of Caoguo Zhimu Decoction(CD)treating epilepsy by using network pharmacology.Methods Traditional Chinese Medicine Systems Pharmacology(TCMSP)and the Comparative Toxicogenomics Database(CTD)were used to obtain targets.The final target of CD for epilepsy was obtained by integrating with Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine,TCMIP v1.0 Universal Protein(UniProt)was used for protein gene translation,Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)was used to obtain Gene ontology(GO)function enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.Results Seventy-five active components of CD and 89 key targets of CD for epilepsy were obtained.The mechanisms involved key targets such as sodium channel protein type 1 subunit alpha(SCN1 A),sodium channel protein type 2 subunit alpha(SCN2 A),sodium channel protein type 8 subunit alpha(SCN8 A),RAC-alpha serine/threonine-protein kinase(AKT1),gamma-aminobutyric acid receptor subunit beta-2(GABRB2),gamma-aminobutyric acid receptor subunit beta-3(GABRB3),gamma-aminobutyric acid receptor subunit delta(GABRD)acting on highly related pathways such as neuroactive ligand-receptor interaction,various synaptic pathways,calcium signaling pathway,estrogen signaling pathway,cell senescence,drug addictions,tobacco and alcohol play the anti-epileptic roles.Conclusions The therapeutic mechanism of CD in treating epilepsy is via multi-targets and multi-pathways.

关 键 词：草果知母汤 癫痫 网络药理学 

分 类 号：R259[医药卫生—中西医结合]