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中国精品科技期刊2020

基于网络药理学与分子对接技术探讨益肝草凉茶解酒保肝的作用机制

王雅芝 张建永 段灿灿

王雅芝,张建永,段灿灿. 基于网络药理学与分子对接技术探讨益肝草凉茶解酒保肝的作用机制[J]. 食品工业科技,2021,42(8):8−18. doi:  10.13386/j.issn1002-0306.2020070092
引用本文: 王雅芝,张建永,段灿灿. 基于网络药理学与分子对接技术探讨益肝草凉茶解酒保肝的作用机制[J]. 食品工业科技,2021,42(8):8−18. doi:  10.13386/j.issn1002-0306.2020070092
WANG Yazhi, ZHANG Jianyong, DUAN Cancan. Mechanism of Relieving Alcohol and Protecting Liver of Yigancao Herbal Tea Based on Network Pharmacology and Molecular Docking Technology[J]. Science and Technology of Food Industry, 2021, 42(8): 8−18. (in Chinese with English abstract). doi:  10.13386/j.issn1002-0306.2020070092
Citation: WANG Yazhi, ZHANG Jianyong, DUAN Cancan. Mechanism of Relieving Alcohol and Protecting Liver of Yigancao Herbal Tea Based on Network Pharmacology and Molecular Docking Technology[J]. Science and Technology of Food Industry, 2021, 42(8): 8−18. (in Chinese with English abstract). doi:  10.13386/j.issn1002-0306.2020070092

基于网络药理学与分子对接技术探讨益肝草凉茶解酒保肝的作用机制

doi: 10.13386/j.issn1002-0306.2020070092
基金项目: 国家自然科学基金项目(81760746);贵州省教育厅科技拔尖人才支持项目(黔教合KY字[2017]078);贵州省科技计划项目(黔科合基础[2020]1Y376,黔科合基础[2019]1346)
详细信息
    作者简介:

    王雅芝(1995−),女,硕士研究生,研究方向:中药质量评价与系统生物学研究,E-mail:2499254895@qq.com

    通讯作者:

    段灿灿(1983−),女,硕士,讲师,研究方向:中药系统生物学研究,E-mail: duancancan2008@126.com

  • 中图分类号: TS255.1

Mechanism of Relieving Alcohol and Protecting Liver of Yigancao Herbal Tea Based on Network Pharmacology and Molecular Docking Technology

  • 摘要: 目的:通过网络药理学方法和分子对接技术,探讨益肝草凉茶解酒保肝的作用机制。方法:利用中药系统药理学分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)、中医药综合数据库(Traditional Chinese Medicines Integrated Database,TCMID)、中药分子机制生物信息学分析工具(A Bioinformatics Analysis Tool for Molecular MechANism of Traditional Chinese Medicine,BATMAN-TCM)、SwissTargetPrediction和TargetNet等数据库,检索益肝草凉茶中9味中药的活性成分及相关靶点;通过比较毒理基因组学数据库(The Comparative Toxicogenomics Database,CTD)、功能关联蛋白网络数据库(Functional Protein Association Networks,STRING)以及蛋白数据库(Universal Protein,Uniprot)数据库获取肝病相关的靶点;通过药物作用靶点及肝病靶点互作筛选益肝草凉茶解酒保肝的靶点,进一步构建解酒保肝靶点的蛋白相互作用网络;通过生物学信息注释数据库(Functional Annotation Bioinformatics Microarray Analysis,DAVID)数据库进行靶点蛋白的基因功能与通路分析;采用Cytoscape软件进行网络构建与分析;借助AutoDock软件,将关键成分与重要靶点进行分子对接验证。结果:本研究共收集到益肝草凉茶的活性成分186个,可作用于298个靶点,其中涉及到肝脏疾病的靶点有78个。预测靶点主要作用于癌症的途径、钙信号通路、神经活性配体-受体相互作用、5-羟色胺能突触、cGMP-PKG信号通路等通路发挥保肝护肝作用。结论:本研究揭示了益肝草凉茶可通过多成分、多靶点、多通路的作用特点调控网络发挥解酒保肝的功效,为其治疗酒精性肝病的研究和临床应用提供科学依据。
  • 图  1  益肝草凉茶解酒保肝作用的系统药理学流程图

    Figure  1.  Systematic pharmacological flow chart of antialcoholic and hepatoprotective effect of Yigancao herbal tea

    图  2  中药-活性成分-靶点网络图

    Figure  2.  Network diagram of traditional Chinese medicine-active ingredient-target

    注:V形代表中药,圆形代表活性成分,六边形代表靶点,四边形代表单味中药之间共有的活性成分。

    图  3  疾病靶点在益肝草凉茶中9味中药的分布图

    Figure  3.  Distribution map of 9 traditional Chinese medicines in Yigancao herbal tea

    图  4  靶蛋白PPI网络

    Figure  4.  Target protein PPI network

    图  5  活性成分相关靶点功能及通路注释分析

    Figure  5.  Analysis of target function and pathway annotation of active components

    图  6  中药-活性成分-作用靶点-主要通路网络图

    Figure  6.  Network diagram of traditional Chinese medicine-active ingredient-action target-main pathway

    图  7  NOS2、PTGS1、ESR1、CYP19A1与结合能排序最低的前2位化合物的最佳对接构象

    Figure  7.  The best docking conformation of NOS2, PTGS1, ESR1, CYP19A1 and the first two compounds with the lowest binding energy

    表  1  中药-活性成分-靶点网络中度值排名前30的化合物信息

    Table  1.   Information of the top 30 compounds in the traditional Chinese medicine-active ingredient-target network

    编号PubChem CID化合物名称来源度值
    C95281855鞣花酸(Ellagic acid)覆盆子84
    C1815460988没食子酸(Gadelaidic acid)甘草79
    C105280343槲皮素(Quercetin)甘草、枸杞子、大枣、栀子、
    苦丁茶、鱼腥草、覆盆子,蒲公英
    73
    C345363269油酸乙酯(NF)(Ethyl oleate (NF))栀子73
    C1803349565二十碳五烯酸(Icos-5-enoic acid)甘草73
    C535281707香豆素(Coumestrol)大枣72
    C315281232番红花酸(Crocetin)栀子71
    C115280863山柰酚(Kaempferol)甘草、栀子、苦丁茶、鱼腥草、覆盆子69
    C29109703765-羟基-7-甲氧基-2-(3,4,5-三甲氧基苯基)
    色原酮 (5-hydroxy-7-methoxy-2-(3,4,5-trimethoxyphenyl)chromone)
    栀子69
    C1705318869熊竹素(Jaranol)甘草69
    C335282184甘露醇(Mandenol)枸杞子、栀子67
    C1835317768刺果甘草查耳酮(Glypallichalcone)甘草66
    C98N/A(E,E)-1-乙基十八烷基-3,13-二烯酸酯
    ((E,E)-1-ethyl octadeca-3,13-dienoate)
    枸杞子65
    C1625316900槲皮素(Quercetin der.)甘草64
    C3052808623-甲基山柰酚(3-Methylkempferol)栀子63
    C139115584521,3-二羟基-9-甲氧基-6-苯并呋喃[3,2-c]
    色原酮(1,3-dihydroxy-9-methoxy-6-benzofurano[3,2-c]chromenone)
    甘草62
    C1425318679异槲皮酚(Isotrifoliol)甘草62
    C1825318999甘草查耳酮B(Licochalcone B)甘草61
    C5210146核黄素(Nuciferin)大枣59
    C1675281654异鼠李素(Isorhamnetin)甘草58
    C1793543687-甲氧基-2-甲基异黄酮 (7-Methoxy-2-methyl isoflavone)甘草58
    C555280537穆坪马兜铃酰胺(Moupinamide)大枣57
    C92N/A7-O-甲基木犀草素-6-C-β-葡萄糖苷_qt (7-O-Methylluteolin-6-C-beta-glucoside_qt)枸杞子56
    C15910881804(E)-1-(2,4-dihydroxyphenyl)-3-(2,2-dimethylchromen-6-yl)prop-2-en-1-one甘草56
    C28638072角鲨烯(Supraene)栀子55
    C12715380912kanzonols W甘草54
    C17692503驴食草酚(Vestitol)甘草54
    C172250157427,2',4'-三羟基-5-甲氧基-3-芳基香豆素
    (7,2',4'-trihydroxy-5-methoxy-3-arylcoumarin)
    甘草52
    C65280378芒柄花黄素(Formononetin)甘草、葛根51
    C161336327苜蓿素(Medicarpin)甘草51
    下载: 导出CSV

    表  2  有效靶点作用于肝病的信息

    Table  2.   Information of effective targets acting on liver disease

    疾病ID疾病名称疾病类别注释基因数量
    MESH:D008107肝病消化系统疾病78
    MESH:D008103肝硬化消化系统疾病|病理学(过程)44
    MESH:D008106肝硬化,实验性消化系统疾病|病理学(过程)35
    MESH:D008113肝肿瘤癌症|消化系统疾病28
    MESH:D006528癌, 肝细胞癌症|消化系统疾病23
    MESH:D056486化学和药物诱导消化系统疾病17
    MESH:D005234肝损伤消化系统疾病13
    MESH:D048550脂肪肝消化系统疾病9
    MESH:D065626肝功能不全消化系统疾病8
    MESH:D002780非酒精性脂肪肝消化系统疾病7
    MESH:D006501胆汁淤积,肝内消化系统疾病|代谢性疾病|6
    MESH:D017093肝性脑病神经系统疾病6
    MESH:D006529肝衰竭消化系统疾病6
    MESH:D008105肝肿大消化系统疾病|病理学(解剖条件)5
    MESH:D058625肝硬化,胆汁性消化系统疾病|病理学(过程)3
    下载: 导出CSV

    表  3  关键成分及对照药与NOS2、PTGS1、ESR1、CYP19A1的结合能

    Table  3.   Binding energy of key components and control drugs with NOS2, PTGS1, ESR1 and CYP19A1

    类别来源化学成分靶点Energy of Binding
    (kcal/mol)
    化学药物熊去氧胆酸
    胶囊
    熊去氧胆酸NOS2−3.83
    PTGS1−2.58
    ESR1−2.78
    CYP19A1−3.47
    化学药物双环醇片双环醇NOS2−1.34
    PTGS1−1.28
    ESR1−0.51
    CYP19A1−1.73
    中药覆盆子鞣花酸NOS2−1.80
    PTGS1−2.88
    ESR1−2.14
    CYP19A1−3.83
    中药甘草没食子酸NOS2−0.13
    PTGS1−0.17
    ESR10.52
    CYP19A1−0.58
    中药甘草,枸杞子,
    大枣,栀子,
    苦丁茶,鱼腥草,
    覆盆子,蒲公英
    槲皮素NOS2−1.93
    PTGS1−2.44
    ESR1−1.65
    CYP19A1−2.23
    中药栀子油酸乙酯NOS20.29
    PTGS10.27
    ESR10.90
    CYP19A10.78
    中药甘草二十碳五烯酸NOS2−0.36
    PTGS10.20
    ESR10.73
    CYP19A10.31
    中药大枣香豆素NOS2−3.35
    PTGS1−3.19
    ESR1−3.25
    CYP19A1−3.96
    中药栀子番红花酸NOS2−2.16
    PTGS1−2.97
    ESR1−2.86
    CYP19A1−2.08
    中药甘草、栀子、
    苦丁茶、鱼腥草、
    覆盆子
    山柰酚NOS2−2.52
    PTGS1−2.59
    ESR1−2.33
    CYP19A1−2.21
    中药栀子5-羟基-7-甲氧基-
    2-(3,4,5-三甲氧基
    苯基)色原酮
    NOS2−2.24
    PTGS1−2.08
    ESR1−1.89
    CYP19A1−2.27
    中药甘草熊竹素NOS2−1.90
    PTGS1−2.51
    ESR1−2.46
    CYP19A1−2.41
    下载: 导出CSV
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  • 收稿日期:  2020-07-09
  • 网络出版日期:  2021-02-27
  • 刊出日期:  2021-04-16

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