摘要
目的采用网络药理学方法及分子对接技术,探讨人参治疗胃癌的作用机制。方法通过中药系统药理学数据库与分析平台搜索人参的有效化学成分及其相应的作用靶点,通过GeneCards数据库、OMIM数据库、DRUGBANK数据库检索胃癌相关靶点,运用Venny 2.1.0软件获取人参有效化学成分作用靶点与胃癌相关靶点的交集靶点。通过STRING数据库构建交集靶点的蛋白-蛋白相互作用(PPI)网络后,应用Cytoscape软件进行可视化处理及网络拓扑学分析以筛选核心靶点。利用STRING数据库构建核心靶点的PPI网络。基于Metascape平台对交集靶点进行基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。使用AutoDock Tools软件对人参主要有效化学成分与核心靶点进行分子对接分析。结果(1)共得到人参有效化学成分24个,作用靶点117个,胃癌相关靶点1921个。人参有效化学成分作用靶点与胃癌相关靶点的交集靶点共60个,筛选出核心靶点21个,包括蛋白激酶B(AKT)1、Jun B原癌基因(JUN)、肿瘤坏死因子(TNF)、前列腺素内过氧化物合酶2(PTGS2)、Caspase-3等。(2)GO功能富集分析和KEGG通路富集分析结果显示,交集靶点涉及88种分子功能,如蛋白质结构域特异性结合、蛋白质同源二聚化活性等;涉及1211个生物过程,如凋亡信号通路、活性氧的代谢过程、对脂多糖的反应等;涉及32种细胞组分,如薄膜筏、细胞质核周区、细胞外基质等;涉及247条信号通路,包括磷脂酰肌醇3-激酶(PI3K)/AKT信号通路、TNF信号通路、丝裂原活化蛋白激酶(MAPK)信号通路等。分子对接结果提示,人参皂苷Rh2、人参皂苷Rh4、山柰酚、β-谷甾醇、豆甾醇均能与AKT1、JUN、TNF结合且大部分化合物与靶点的结合性良好。结论人参主要有效化学成分有人参皂苷Rh2、人参皂苷Rh4、山柰酚、β-谷甾醇、豆甾醇,它们通过作用于核心靶点AKT1、JUN、TNF,主要在薄膜筏、细胞质核周区、细胞外基质中参与细胞凋亡、活性氧的代谢过程、炎症反应等进程,作用于PI3K/AKT信号通路、TNF信号通路、MAPK信号通路等关键信号通路,从而发挥治疗胃癌的作用。
Objective To explore the mechanism of ginseng for the treatment of gastric cancer by employing network pharmacology and molecular docking technique.Methods The effective chemical components and their corresponding effect targets of ginseng were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The targets related to gastric cancer were retrieved from the databases of GeneCards,OMIM,and DRUGBANK.The intersection targets of effect targets of effective chemical components of ginseng with gastric cancer related targets were obtained by using Venny 2.1.0 software.The protein-protein interaction(PPI)network of intersection targets was established by STRING database,and then visual processing and network topology analysis were performed to screen the core targets by employing Cytoscape software.The PPI network of core targets was established by the application of STRING database.The Gene Oncology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on intersection targets based on Metascape platform.The molecular docking analysis was performed on main effective chemical components and the core targets of ginseng by using AutoDock Tools software.Results(1)A total of 24 effective chemical components of ginseng,117 corresponding effect targets,and 1921 targets related to gastric cancer were obtained.There were 60 intersection targets between effect targets of effective chemical components of ginseng and gastric cancer related targets,and 21 core targets were screened,including protein kinase B(AKT)1,Jun B proto-oncogene(JUN),tumor necrosis factor(TNF),prostaglandin-endoperoxide synthase 2(PTGS2),Caspase-3,etc.(2)The results of GO functional enrichment analysis and KEGG pathway enrichment analysis revealed that the intersection targets involved 88 molecular functions with respect to protein domain specific binding and protein homologous dimerization activity,etc.,1211 biological processes in terms of apoptotic signaling pathways,reactive oxygen metabolism,reaction to lipopolysaccharide,etc.,32 cell compositions,such as membrane raft,perinuclear region of cytoplasm,extracellular matrix,etc.,and 247 signaling pathways,including phosphoinositide 3-kinase(PI3K)/AKT signaling pathway,TNF signaling pathway,mitogen-activated protein kinase(MAPK)signaling pathway,etc.The results of molecular docking indicated that ginsenoside Rh2,ginsenoside-Rh4_qt,kaempferol,β-sitosterol,and stigmasterol could be combined with AKT1,JUN,and TNF,and most of the chemical compounds exerted favorable bindings with targets.Conclusion The main effective chemical components of ginseng involve ginsenoside Rh2,ginsenoside-Rh4_qt,kaempferol,β-sitosterol,and stigmasterol,and they play a role in the treatment of gastric cancer by acting on the core targets of AKT1,JUN and TNF,and participating in cell apoptosis,reactive oxygen metabolism,inflammatory responses and other processes mainly in membrane rafts,perinuclear region of cytoplasm,extracellular matrix,and acting on PI3K/AKT signaling pathway,TNF signaling pathway,MAPK signaling pathway and other key signaling pathways.
作者
卢鑫
尹硕鑫
江水玉
李清梅
覃靖燊
张涛
陈远能
LU Xin;YIN Shuoxin;JIANG Shuiyu;LI Qingmei;QIN Jingshen;ZHANG Tao;CHEN Yuanneng(Graduate School,Guangxi University of Chinese Medicine,Nanning 530000,Guangxi,China;Department of Gastroenterology,Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine,Nanning 530011,Guangxi,China)
出处
《广西医学》
CAS
2023年第7期796-803,共8页
Guangxi Medical Journal
基金
国家自然科学基金(81360531)
广西自然科学基金(2020GXNSFAA238030)
广西中医药大学硕士研究生科研创新项目(xjyb112)。
关键词
胃癌
人参
人参皂苷
网络药理学
分子对接
作用机制
Gastric cancer
Ginseng
Ginsenoside
Network pharmacology
Molecular docking
Mechanism
作者简介
第一作者:卢鑫,硕士,住院医师,研究方向:消化系统疾病中西医结合防治研究;通信作者:张涛,博士后,主任医师,研究方向:中医药治疗消化系统疾病的基础与临床研究。
