基于血清药物化学和网络药理学的蛇莓抗炎药效物质基础和作用机制研究  

Pharmacodynamic material basis and mechanisms of anti-inflammatory effect of Duchesnea indica based upon serum pharmacochemistry and network pharmacology

作　　者：陈笑天 廖君 李聪 梁勇 肖欢 乐颖娜 熊磊 CHEN Xiaotian;LIAO Jun;LI Cong;LIANG Yong;XIAO Huan;LE Yingna;XIONG Lei(College of Pharmacy,Nanchang Medical College,Jiangxi Nanchang 330052,China;College of Pharmacy,Jiangxi University of Chinese Medicine,Jiangxi Nanchang 330004,China;Department of Medical affair,The First Affiliated Hospital of Nanchang University,Jiangxi Nanchang 330006,China)

机构地区：[1]南昌医学院药学院,江西南昌330052 [2]江西中医药大学药学院,江西南昌330004 [3]南昌大学第一附属医院医务处,江西南昌330006

出　　处：《中国医院药学杂志》2024年第14期1635-1644,共10页Chinese Journal of Hospital Pharmacy

基　　金：江西省教育厅科技项目(编号:GJJ218921);江西省教育厅科技项目(编号:GJJ2203521);南昌医学院科技创新团队项目(编号:NYTD202202)。

摘　　要：目的:基于血清药物化学研究方法结合网络药理学与分子对接研究蛇莓发挥抗炎作用的药效物质基础和作用机制。方法:大鼠灌胃给予蛇莓水提液,眼眶取血并分离血清。采用超高效液相色谱-四极杆-飞行时间质谱(UPLC-Q-TOF-MS)技术,结合Agilent Masshunter Qualitative Analysis数据处理系统,通过对比蛇莓水提液、空白血清和含药血清,结合对照品、二级谱图和已有文献,对蛇莓入血成分进行鉴定。利用SwissTargetPrediction数据库获取入血成分靶点,Genecards、Drugbank数据库获得疾病靶点。利用Jvenn网站取成分靶点和疾病靶点的交集,通过String数据库绘制蛋白相互作用关系(protein-protein interaction,PPI)网络图,利用DAVID数据库对交集靶点进行基因本体(Gene Ontology,GO)功能富集分析和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。使用Autodock软件对入血成分与核心靶点进行分子对接,使用Pymol软件对分子对接的结果进行可视化处理。结果:根据质谱分子量、碎片裂解规律并结合对照品、文献及数据库等相关信息,从大鼠含药血清当中鉴定出27个原型入血成分,包括黄酮类9个,有机酸类8个,苯丙素4个,香豆素3个,三萜类2个,醛类1个。化合物和疾病共有靶点356个,通过PPI网络筛选出SRC、EGFR、AKT1、TNF等11个核心靶点。KEGG分析结果显示蛇莓主要通过调控EGFR酪氨酸激酶抑制剂耐药性通路、TNF信号通路、ErbB信号通路、HIF-1信号通路等发挥作用。对关键成分与核心靶点进行分子对接,结果显示蛇莓关键成分与核心靶点的结合能力良好。结论:所建立的方法能高效、灵敏地分析蛇莓的入血成分。蛇莓中的金丝桃苷、紫云英苷、木犀草素等黄酮类物质和鞣花酸等酚酸类物质可能是其发挥抗炎作用的药效物质,并通过EGFR、HIF-1、TNF等通路调节炎症反应从而发挥药理作用。该研OBJECTIVE To explore the pharmacodynamic material basis and mechanisms of anti-inflammatory effect of Duchesnea indica based upon serum pharmacochemistry,network pharmacology and molecular docking.METHODS Duchesnea indica Decoction was dosed by intragastric administration into the rats.Serum samples were harvested from ocular orbit.Ultra high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS)technology and Agilent Masshunter Qualitative Analysis data processing system were employed for comparing Duchesnea indica Decoction,blank sera and drug-containing sera.And absorbed components in sera were analyzed with reference substance,MS/MS profiles in related database and literature.The targets of absorbed components in sera were retrieved from Swisstargetprediction database while the targets of disease retrieved from the databases of Genecards and Drugbank.Compound target-disease target intersection was obtained through Jvenn website and STRING database utilized for constructing the protein-protein interaction(PPI)network of intersection targets.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed on target genes by DAVID database.Autodock software was utilized for molecular docking and Pymol software for visualizing the results of molecular docking.RESULTS According to mass spectrum molecular weight,fragmentation,related information from reference substance,literature and database,27 prototype absorbed components were identified from drugcontaining sera,including 9 flavonoids,8 organic acids,4 phenylpropanoids,3 coumarins,2 triterpenoids and 1 aldehyde.There were 356 common targets from compounds and diseases and 11 core targets(SRC,EGFR,AKT1&TNF)were screened through PPI network.KEGG analysis revealed that the role of this plant was achieved mainly through regulating the pathways of EGFR tyrosine kinase inhibitor resistance and TNF/ErbB/HIF-1 signaling.Molecular docking between critical components and core target showed that bin

关 键 词：蛇莓 UPLC-Q-TOF-MS 血清药物化学 药效物质基础 网络药理学 分子对接 

分 类 号：R284.1[医药卫生—中药学] R914[医药卫生—中医学]