基于GC-MS与网络药理学的青皮挥发油防治阿尔茨海默症的活性成分及作用机制研究  

Study on Active Components and Mechanism of Volatile Oil of Citri reticulatae Preventing and Treating Alzheimer's Disease Based on GC-MS and Network Pharmacology

作　　者：王腾华 罗颖懿 王驭辰 任之尧 唐建新 李咏梅[1] 方翼 吴波 WANG Tenghua;LUO Yingyi;WANG Yuchen;REN Zhiyao;TANG Jianxin;LI Yongmei;FANG Yi;WU Bo(Depl.of Phamagy,the Fifh Aliated Hopital of Gungzhou Meltical Uiesityt Guanghou 50700,China;Dept,of Pharmacy,Sun Yat-sen Memorial Hospital of Sun Yat-sen University,Guangzhou 510120,China;Senior School Section,Shenzhen Middle School,Guangdong Shenzhen 518001,China;College of Chinese Medicine,Guangzhou University of TCM,Guangzhou 510006,China;School of Pharmaceutical Sciences,Guangzhou Medical University,Guangzhou 511436,China)

机构地区：[1]广州医科大学附属第五医院药学部,广州510700 [2]中山大学孙逸仙纪念医院药学部,广州510120 [3]深圳中学高中部,广东深圳518001 [4]广州中医药大学中药学院,广州510006 [5]广州医科大学药学院,广州511436

出　　处：《中国药房》2020年第17期2093-2100,共8页China Pharmacy

基　　金：重大新药创制科技重大专项(NO.2020ZX09201026);广州医科大学2016年校级科研项目。

摘　　要：目的:预测青皮挥发油防治阿尔茨海默病(AD)的主要活性成分和潜在作用靶点。方法:采用气质联用技术(GC-MS)分析青皮挥发油化学成分,并借助NIST 11.L数据库和人工数据解析进行成分的结构鉴定。借助中药系统药理学分析平台(TCMSP)、PharmMapper数据库等预测青皮挥发油活性成分及其对应靶点,借助GeneCards数据库、人类孟德尔遗传数据库等挖掘AD相关靶点;利用Venny 2.1.0软件映射以获取青皮挥发油防治AD的直接靶点;借助STRING数据库和Cytoscape 7.2.1软件挖掘核心节点,利用Venny 2.1.0软件映射并去重后获取青皮挥发油防治AD的间接靶点;借助DAVID 6.7数据库对上述直接和间接靶点(即作用靶点)进行基因本体(GO)功能富集和KEGG通路富集分析;采用Cytoscape 7.2.1软件,以节点度值、介数中心度、紧密中心度为指标,对青皮挥发油"活性成分-作用靶点"网络进行拓扑学分析,挖掘关键成分和关键靶点。结果与结论:GC-MS法共分离并鉴定出青皮挥发油化学成分40个,均为活性成分,包括右旋柠檬烯、γ-萜品烯等。共挖掘出活性成分对应靶点151个、AD相关靶点1291个,其中直接靶点48个、间接靶点41个。上述89个作用靶点主要富集于细胞分数、轴突、胞浆等细胞组分,细胞内信号级联、对有机物的反应等生物过程,蛋白激酶活性、胺受体活性等分子功能,以及癌症通路、钙信号通路、神经营养素信号通路等信号通路(P<0.05)。共挖掘出α-萜品烯、β-elemen、百里酚、(-)-4-萜品醇等关键成分10个,雄激素受体(AR)、前列腺素G/H合酶2(PTGS2)、丝裂原活化蛋白激酶14、毒蕈碱乙酰胆碱受体M1等关键靶点21个,表明青皮挥发油防治AD呈多成分、多靶点、多通路的作用特点。OBJECTIVE:To predict the active components and potential target of volatile oil of Citri reticulatae preventing and treating Alzheimer’s disease(AD).METHODS:The volatile oil of C.reticulatae was determined by GC-MS,and identified according to NIST 11.L database and manual data analysis.The active components and targets of volatile oil of C.reticulatae were predicted through TCMSP and PharmMapper database.The related targets of AD were obtained by using GeneCards and OMIM databases.Venny 2.1.0 software mapping was used to obtain the direct targets of volatile oil of C.reticulatae against AD.Core nodes were mined with STRING database and Cytoscape 7.2.1 software,and the indirect targets of volatile oil of C.reticulatae against AD were obtained by mapping and duplication coith Venny 2.1.0 software.With the help of DAVID 6.7 database,the above direct and indirect targets(i.e.action targets)were used for gene ontology(GO)function enrichment analysis and KEGG pathway enrichment analysis.Using Cytoscape 7.2.1 software,topology analysis was conducted for the network of"active componentsacting targets"of volatile oil of C.reticulatae,with node degree value,betweenness centrality and closeness centrality as indexes,then key components and key targets were mined.RESULTS&CONCLUSIONS:A total of 40 chemical components in volatile oil were identified by GC-MS,all of them were active components,including D-limonene,γ-terpinene,etc.A total of 151 active components-corresponding targets and 1291 AD-related targets were mined,including 48 direct targets and 41 indirect targets.The above 89 targets were mainly concentrated in cell fraction,axon,cytosol and other cell components;intracellular signaling cascade,response to organic substance and other biological processes;protein kinase activity and amine receptor activity and other molecular functions;as well as cancer pathway,calcium signaling pathway and neurotrophin signaling pathway(P<0.05).A total of 10 key components includingα-terpinene,β-elemen,thymol and(-)-4-terpineol,a

关 键 词：青皮 挥发油 气质联用技术 网络药理学 阿尔茨海默病 机制 

分 类 号：R284.2[医药卫生—中药学] R285[医药卫生—中医学]