摘要
目的:利用网络药理学和分子对接技术探讨西洋参茎叶三醇组皂苷(PQTS)在缺血性脑卒中(IS)发生发展过程中潜在的作用机制。方法:整合Swiss Target Prediction、中医药百科全书(ETCM)、 SEA Search Server和DisGeNET等数据库获取PQTS作用于IS的潜在靶点。利用STRING数据库和Cytoscape 3.9.1软件构建潜在作用靶点的蛋白-蛋白互作(PPI)网络,并通过拓扑网络分析得到PQTS作用于IS的核心靶点。通过DAVID在线分析网站进行潜在作用靶点的基因本体(GO)功能和京都基因与基因组百科全书(KEGG)信号通路富集分析,获取相关信号通路。应用Cytoscape 3.9.1软件构建PQTS-靶点-信号通路网络,进行拓扑网络分析,筛选PQTS潜在主要活性成分。通过AutoDock Vina软件对活性成分和核心靶点进行分子对接验证。结果:得到PQTS作用IS的潜在作用靶点122个,GO功能富集分析主要涉及细胞凋亡调控、细胞内信号传导过程和细胞对外源性物质的调控等生物学过程,KEGG富集分析涉及白细胞介素信号通路、磷脂酰肌醇3-激酶/蛋白激酶B (PI3K/Akt)信号通路和PI3K/Akt/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路。分子对接分析,拟人参皂苷F11、20 (S)-原人参三醇、人参皂苷Rg1、人参皂苷Rh1、拟人参皂苷RT5和人参皂苷Re与信号转导和转录激活因子3 (STAT3)、磷脂酰肌醇3-激酶催化亚基α (PIK3CA)、表皮生长因子受体(EGFR)和丝裂原活化蛋白激酶14 (MAPK14)均能形成结合能较低的稳定构象。结论:PQTS对IS的保护作用可能与STAT3、PIK3CA、EGFR和MAPK14及PI3K/Akt信号通路有关。
Objective:To discuss the potential mechanism of Panax quinquefolium triolsaponins(PQTS)in the occurrence and development of ischemic stroke by using network pharmacology and molecular docking technique.Methods:The potential targets of PQTS acing on IS were obtained through Swiss Target Prediction Database,Encyclopedia of Traditional Chinese Medicine(ETCM)Database,SEA Search Server Database,DisGeNET Database,and so on;the protein-protein interaction(PPI)network diagram of the key potential targets was established by STRING Database and Cytoscape 3.9.1 software;the core tagets of PQTS acting on IS were got by topology network analysis;Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were used to analyze the potential targets through DAVID online analysis website;the PQTStarget-signaling pathway network was constructed by Cytoscape 3.9.1 software and the topology network analysis was used to obtain the potential main active compositions;AutoDock Vina software was used to verify the molecular docking between the active ingredients and core targets.Results:There were 122 potential targets of PQTS acting on IS;the GO function enrichment analysis was mainly included the regulation of apoptosis,intracellular signal transduction process,and regulations of extracellular substances by cells;the KEGG function analysis included the interleukins signaling pathways,phosphatidylinositol 3 kinase/protein kinase B(PI3K/Akt)signaling pathway and phosphatidylinositol 3 kinase-protein kinase B-mammalian target of rapamycin(PI3K-Akt-mTOR)signaling pathway.The molecular docking analysis results showed that pseudo-ginsenoside F11,20(S)-protopanaxatriol,ginsenoside Rg1,ginsenoside Rh1,pseudo-ginsenoside RT5,and ginsenoside Re could form the stable conformations with signal transducer and activator of transcription 3(STAT3),phosphatidylinositol 3-kinases catalytic suburitα(PIK3CA),epidermal growth factor receptor(EGFR),and mitogen-activated protein kinase 14(MAPK14)with lowe
作者
赖思含
刘俊彤
谭璐瑩
刘金平
李平亚
LAI Sihan;LIU Juntong;TAN Luying;LIU Jinping;LI Pingya(Research Center of Natural Drug,School of Pharmaceutical Sciences,Jilin University,Changchun 130021,China)
出处
《吉林大学学报（医学版）》
CAS
CSCD
北大核心
2023年第4期913-922,共10页
Journal of Jilin University：Medicine Edition
基金
吉林省科技厅重大科技专项项目(20200504006YY)。
