基于网络药理学研究三七治疗血小板聚集的作用机制

Mechanism of Panax notoginsengin treatment of platelet aggregation based on network pharmacology

目的通过网络药理学研究三七治疗血小板聚集的作用机制。方法查询中药系统药理学数据库与分析平台(TCMSP)数据库筛选三七的药物成分,使用Swiss Target Prediction预测药物成分的作用靶点;运用GeneCards获取血小板聚集的疾病靶点,利用venny 2.1获取交集靶点。使用String进行蛋白质-蛋白质相互作用(PPI)分析并使用Cytoscape构建网络图,使用Cytoscape软件构建“药物-靶点-通路”网络图。利用Metascape进行基因本体(GO)富集分析及京都基因和基因组百科全书(KEGG)信号通路分析。结果三七中的7个有效成分通过多条通路直接作用于142个疾病靶点治疗血小板聚集,其中β-谷甾醇、豆甾醇、槲皮素和人参皂苷Rh2等是核心成分,肿瘤蛋白p53(TP53)、丝裂原活化蛋白激酶1(MAPK1)、JUN、肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)、蛋白激酶B1(AKT1)是重要靶点。GO富集分析显示,生物过程(BP)主要涉及细胞对脂质的反应、对激素的反应、细胞对氮化合物的反应等;细胞组分(CC)主要涉及膜筏、膜微区、小窝和质膜筏等;分子功能(MF)主要涉及DNA结合转录因子结合、转录因子结合、RNA聚合酶Ⅱ特异度DNA结合转录因子结合等。KEGG通路富集分析表明,三七治疗血小板聚集的信号通路主要有晚期糖基化终末产物-晚期糖基化终末产物受体(AGE-RAGE)、磷脂酰肌醇-3-激酶(PI3K)/Akt、缺氧诱导因子-1(HIF-1)、TNF、MAPK等。结论三七主要通过调节AGE-RAGE、PI3K/Akt、HIF-1、TNF、MAPK等信号通路的TP53、MAPK1、JUN、TNF、IL-6、AKT1等疾病靶点,调节酶类活性治疗血小板聚集。

Objective To study the mechanism of Panax notoginseng in treatment of platelet aggregation based on network pharmacology.Methods Traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)was queried to screen the drug components of P.notoginseng,and Swiss Target Prediction was used to predict the target of drug components.The GeneCards database was used to obtain disease targets for platelet aggregation,and Venny 2.1 was used to obtain intersection targets.Protein-protein interaction(PPI)was analyzed with String and network diagram with the Cytoscape.The drug-target-pathway network map was constructed by using the Cytoscape software.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)were analyzed with the Metascape.Results Seven active components of P.notoginseng directly acted on 142 disease targets through multiple pathways to treat platelet aggregation.Among them,β-sitosterol,stigmasterol,quercetin,and ginsenoside Rh2 were core components.Tumor protein p53(TP53),mitogen-activated protein kinase 1(MAPK1),JUN,tumor necrosis factor(TNF),interleukin-6(IL-6),and protein kinase B1(AKT1)are critical targets.GO enrichment analysis found that biological process(BP)most likely related to cell response to lipids,hormone response,and cell response to nitrogen compounds;Cell components(CC)mainly involved membrane rafts,membrane microregions,pits,and plasma membrane rafts.Molecular functions(MF)mainly involve DNA binding transcription factor binding,transcription factor binding,RNA polymeraseⅡspecific DNA binding transcription factor binding,etc.KEGG pathway analysis suggested that P.notoginseng was mainly involved in advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE),phosphatidylinositol 3-kinase(PI3K)/Akt,hypoxia inducible factor-1(HIF-1),TNF,and MAPK.Conclusions P.notoginseng mainly regulates disease targets such as TP53,MAPK1,JUN,TNF,IL6,and AKT1 in AGE-RAGE,PI3K/AKT,HIF-1,TNF,MAPK,and other signaling pathways,and regulates enzyme activity to treat platelet aggregation.