基于网络药理学及实验验证探究荆芥挥发油治疗抑郁症的作用机制  

Mechanism of essential oil from Schizonepeta tenuifolia in treatment of depression based on network pharmacology and experimental verification

作　　者：秦甜甜 谢红潇 胡靖文 曾九僧 刘蓉[1,2] 曾南[1,2] QIN Tian-tian;XIE Hong-xiao;HU Jing-wen;ZENG Jiu-seng;LIU Rong;ZENG Nan(State Key Laboratory of Southwestern Chinese Medicine Resources,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China;College of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China)

机构地区：[1]成都中医药大学西南特色中药资源国家重点实验室,四川成都611137 [2]成都中医药大学药学院,四川成都611137

出　　处：《中国中药杂志》2023年第4期1066-1075,共10页China Journal of Chinese Materia Medica

基　　金：西南特色中药资源国家重点实验室开放研究基金项目(2020XSGG002);国家自然科学基金项目(82074094)。

摘　　要：采用网络药理学方法,结合脂多糖(LPS)诱导的抑郁样小鼠模型,探究荆芥挥发油的抗抑郁作用及相关机制。采用GC-MS技术对荆芥挥发油化学成分进行鉴定,选取荆芥挥发油中12种活性成分为研究对象;利用中医药系统药理学数据库及分析平台(TCMSP)、成分靶点预测数据库(SwissTargetPrediction)获取荆芥挥发油的作用靶点;通过基因数据库(GeneCards)、疗效药靶数据库(TTD)和在线人类孟德尔遗传病数据库(OMIM)获取抑郁症相关靶点,利用软件Venny 2.1筛选出荆芥挥发油与抑郁症的共有靶标;将其导入Cytoscape 3.7.2软件,生成“药物-活性成分-疾病-靶点”网络图;采用STRING 11.5数据库和Cytoscape 3.7.2软件构建蛋白-蛋白互作(protein-protein interaction,PPI)网络,并筛选核心靶点。利用DAVID 6.8进行基因本体(Gene Ontology,GO)功能及京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析,随后通过微生信云平台对富集结果可视化。采用腹腔注射LPS制备抑郁样小鼠模型,造模前灌胃给予荆芥挥发油,造模后进行悬尾实验、强迫游泳实验和新奇环境抑制进食实验,评价荆芥挥发油的抗抑郁作用;酶联免疫法(ELISA)检测小鼠血清白细胞介素-1β(interleukin-1β,IL-1β)含量;蛋白质免疫印记法(Western blot)检测小鼠海马组织pro IL-1β、IL-1β蛋白表达水平。荆芥挥发油中的12个主要成分,对应179个靶点,其中116个和抑郁症相关;主要涉及神经活性配体-受体相互作用、钙信号通路、环磷腺苷(cyclic adenosine monophosphate,cAMP)信号通路等;通过突触信号传导、G蛋白偶联受体信号通路、化学突触传递等生物过程,神经递质受体活性、核受体活性、血红素结合等分子功能发挥作用。小鼠实验表明,与模型组比较,荆芥挥发油100、50 mg·kg-1能显著缩短小鼠强迫游泳和悬尾实验中不动时间及新奇摄食实验中的摄食潜伏期,明This paper aimed to explore the antidepressant effect of the essential oil from Schizonepeta tenuifolia Briq.(EOST) on the treatment of depression and its mechanism by using a combination of network pharmacology and the mouse model of lipopolysaccharide(LPS)-induced depression. The chemical components in EOST were identified using gas chromatography-mass spectrometer(GC-MS), and 12 active components were selected as the study objects. The targets related to EOST were obtained by Traditional Chinese Medicines Systems Pharmacology(TCMSP) and SwissTargetPrediction database. The targets related to depression were screened out through GeneCards, Therapeutic Target Database(TTD), and Online Mendelian Inheritance in Man(OMIM) database. The Venny 2.1 was applied to screen out the common targets of EOST and depression. The targets were imported into Cytoscape 3.7.2 to generate "drug-active component-diease-target" network diagram. The protein-protein interaction(PPI) network was constructed using STRING 11.5 database and Cytoscape 3.7.2, and the core targets were screened out. DAVID 6.8 database was used for Gene Ontology(GO) func-tional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis, and subsequently the enrichment results were visualized through the bioinformatics platform. The mouse model of depression was induced by intraperitoneally injecting with LPS in mice. Before modeling, mice were administrated orally with EOST. The antidepressant effect of EOST was evalua-ted by tail suspension test(TST), forced swimming test(FST), and novelty suppressed feeding test(NSFT) after modeling. The content of interleukin(IL)-1β was determined by enzyme-linked immunosorbent assay(ELISA), and the protein expression levels of IL-1β and pro IL-1β in the hippocampus were determined by Western blot. There were 12 main components and 179 targets in EOAT, of which, 116 targets were related to depression, mainly involved in neuroactive ligand-receptor interaction, calcium signaling pathwa

关 键 词：荆芥挥发油 网络药理学 抑郁症 脂多糖 小鼠 机制 

分 类 号：R285[医药卫生—中药学]