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基于超高效液相色谱-四级杆飞行时间串联质谱和网络药理学的甘枣宁治疗非酒精性脂肪性肝病药效物质基础研究
引用本文:王婉先,姚曼,余钦,李一璇,凌昌全.基于超高效液相色谱-四级杆飞行时间串联质谱和网络药理学的甘枣宁治疗非酒精性脂肪性肝病药效物质基础研究[J].中草药,2021,52(12):3591-3601.
作者姓名:王婉先  姚曼  余钦  李一璇  凌昌全
作者单位:上海中医药大学, 上海 201203;海军军医大学中医系, 上海 200433;海军军医大学附属长海医院中医肿瘤科, 上海 200433;上海中医药大学附属岳阳医院, 上海 200437
摘    要:目的探究甘枣宁的主要活性成分,预测并验证其治疗非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)的主要物质基础。方法采用超高效液相色谱-四级杆飞行时间串联质谱(UPLC-Q-TOF-MS/MS),明确甘枣宁水煎液的化学成分。采用网络药理学方法检索甘枣宁活性成分及其潜在靶点,将药物靶点与NAFLD相关靶点取交集,进行蛋白质与蛋白质相互作用(protein-protein interaction,PPI)、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。考察甘枣宁水煎液及(S)-N-衡州乌药碱、(R)-N-衡州乌药碱、N-去甲基亚美罂粟碱、O-去甲基荷叶碱、(-)-表儿茶素和N-去甲基荷叶碱6个关键活性成分对小鼠单核巨噬细胞RAW264.7上清液一氧化氮水平的影响;考察甘枣宁水煎液及N-去甲基荷叶碱对RAW264.7细胞存活率的影响。结果从甘枣宁水煎液鉴定出96个主峰成分,网络药理学分析出甘枣宁治疗NAFLD的活性成分31个,所对应的相关靶点42个,其中一氧化氮合酶3(nitric oxide synthase 3,NOS3)、白细胞介素-6(interleukin-6,IL-6)等靶点关联性较强;甘枣宁治疗NAFLD主要涉及糖尿病并发症中的晚期糖基化终末产物(advanced glycation end products,AGEs)及其糖基化终末产物受体(receptor for advanced glycation end products,RAGE)通路、程序性坏死等通路。甘枣宁水煎液具有良好的抗炎活性,N-去甲基荷叶碱可能为其发挥抗炎作用的关键成分。结论甘枣宁治疗NAFLD具有多成分、多靶点的特点,其药效物质基础与抗炎相关。

关 键 词:甘枣宁  非酒精性脂肪性肝病  超高效液相色谱-四级杆飞行时间串联质谱  网络药理学  N-去甲基荷叶碱
收稿时间:2020/12/16 0:00:00

Pharmacodynamic material basis of Ganzaoning for treatment of non-alcoholic fatty liver disease based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and network pharmacology
WANG Wan-xian,YAO Man,YU Qin,LI Yi-xuan,LING Chang-quan.Pharmacodynamic material basis of Ganzaoning for treatment of non-alcoholic fatty liver disease based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and network pharmacology[J].Chinese Traditional and Herbal Drugs,2021,52(12):3591-3601.
Authors:WANG Wan-xian  YAO Man  YU Qin  LI Yi-xuan  LING Chang-quan
Affiliation:Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;Department of Traditional Chinese Medicine, the Second Military Medical University, Shanghai 200433, China;Department of Traditional Chinese Medicine Oncology, Changhai Hospital Affiliated to the Second Military Medical University, Shanghai 200433, China;Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
Abstract:
Keywords:Ganzaoning  non-alcoholic fatty liver  ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry  network pharmacology  N-nornuciferine
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