基于HPLC-Q-TOF/MS和网络药理学的清心滋肾方防治绝经综合征潜在药效物质基础和作用机制研究  

Investigation of potential pharmacodynamic substances and mechanism of Qingxin-zishen prescription decoction in treatment of menopause syndrome based on HPLC-Q-TOF-MS/MS and network pharmacology

作　　者：姚倩 陈赟[1] 商娟 袭晓昀 陈影 顾潇 居文政[1] 邹建东[1] 卢苏[1] 许美娟[1] YAO Qian;CHEN Yun;SHANG Juan;XI Xiaoyun;CHEN Ying;GU Xiao;JU Wenzheng;ZOU Jiandong;LU Su;XU Meijuan(Affiliated Hospital of Nanjing University of Chinese Medicine,Jiangsu Provincial Hospital of Traditional Chinese Medicine,Nanjing 210029,Jiangsu,China;Huaian Hospital of Traditional Medicine,Huaian 223001,Jiangsu,China;Nanjing University of Chinese Medicine,Nanjing 210023,Jiangsu,China)

机构地区：[1]南京中医药大学附属医院江苏省中医院,江苏南京210029 [2]淮安市中医院,江苏淮安223001 [3]南京中医药大学,江苏南京210023

出　　处：《中国临床药理学与治疗学》2022年第5期481-497,共17页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金(81574009);江苏省卫计委科研课题(Q201602);江苏省研究生科研与实践创新计划(SJCX20_0580);南京中医药大学自然科学基金面上项目(XZR2020015)。

摘　　要：目的:借助高效液相色谱-四级杆飞行时间串联质谱(HPLC-Q-TOF/MS)技术结合网络药理学的方法,分析清心滋肾方的化学成分,预测其防治绝经综合征(MPS)的药效的物质基础和作用机制。方法:分析色谱峰保留时间、精确相对分子质量、二级质谱裂解碎片等信息,与已建的化学成分数据库和文献对比,鉴定出清心滋肾方的化学成分。借助中药系统药理学数据库和分析平台(TCMSP)和SwissTargetPrediction数据库预测清心滋肾方成分靶点;利用人类孟德尔遗传数据库(OMIM)及GeneCards数据库检索疾病靶点。经Metascape数据库对潜在靶点进行基因本体(GO)注释和京都基因与基因组百科全书(KEGG)通路富集分析,用Cytoscape 3.7.2软件构建“活性成分-核心靶点-通路”网络图,并经AutoDockTools 4.2.5软件对清心滋肾方的核心活性成分与核心靶点进行分子对接验证。结果:从清心滋肾方共鉴定出83个化学成分,预测出847个药物靶点,检索出3050个疾病靶点,获得共同靶点395个。经网络拓扑分析,获得74个核心靶点,主要涉及MAPK信号通路、磷脂酰肌醇-3激酶-蛋白激酶B(PI3K-Akt)信号通路和转化生长因子-β(TGF-β)等19条信号通路。分子对接结果表明小檗碱、表小檗碱、黄连碱、缝籽嗪甲醚、莲心碱、去甲基衡州乌药碱、巴马汀、槲皮素和木犀草素等成分与部分核心靶点有较好的结合活性。结论:本研究初步鉴定了清心滋肾方水煎液防治绝经综合征潜在的有效成分并预测了其作用靶点,为该方药效物质基础及作用机制的深入研究提供了参考。AIM:To analyze the chemical ingredients of Qingxin-zishen prescription decoction(QZPD)and predict its main pharmacodynamic substances and mechanism in the prevention and treatment of menopause syndrome(MPS)with the help of high performance liquid chromatography-quadrupole-time of flight mass spectrometry(HPLC-Q-TOF/MS)combined with network pharmacology.METHODS:The chemical ingredients of QZPD were identified after analyzing the retention time,exact mass,secondary mass spectrometry fragmentation and other information obtained from HPLC-Q-TOF/MS and comparing them with the established chemical ingredients database and the literatures.The targets of ingredients in QZPD were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and SwissTargetPrediction database.The disease targets of MPS were obtained through Online Mendelian Inheritance in Man(OMIM)and GeneCards Database.Gene ontology(GO)function enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of potential targets were analyzed with the Metascape database.Cytoscape 3.7.2 software was used to construct the network of active components-key targets-pathways.AutoDockTools 4.2.5 software was applied in the molecular docking verification between the key active components and key targets.RESULTS:A total of 83 components were identified in QZPD and 847 drug targets were predicted.After intersection them with 3050 disease targets,395 common targets were obtained.After network topology analysis,74 key targets were obtained,involving mitogen-activated protein kinase(MAPK),phosphatidylinositol-3 kinase/protein kinase B(PI3K/Akt),transforming growth factor-β(TGF-β)and other signaling pathways.Molecular docking analysis results indicated that 23 key active components,such as berberine,epiberberine,coptisine,geissoschizine methyl ether,liensinine,norcoclaurine,palmatine,quercetin,and luteolin,had good binding activity with several of the key targets.CONCLUSION:This study preliminarily identifies the pote

关 键 词：清心滋肾方 绝经综合征 网络药理学 HPLC-Q-TOF/MS 分子对接 信号通路 

分 类 号：R965.2[医药卫生—药理学]