天然产物研究与开发 ›› 2021, Vol. 33 ›› Issue (增刊1): 127-136.doi: 10.16333/j.1001-6880.2021.S.015

• 数据研究 • 上一篇    下一篇

基于网络药理学和分子对接技术探讨越鞠丸治疗非酒精性脂肪肝病的潜在靶点和作用机制

彭小园,王月,彪雅宁,李易水,王杨,步洁,张一昕*


  

  1. 河北中医学院药学院,河北省高校中药组方制剂应用技术研究中心,石家庄 050200
  • 出版日期:2021-08-28 发布日期:2021-09-08
  • 基金资助:
    河北省自然科学基金(H2020423028);河北省中医药管理局科研计划(2019036)

Study on the potential targets and mechanism of Yueju pills in the treatment of nonalcoholic fatty liver disease based on network pharmacology and molecular docking

PENG Xiao-yuan,WANG Yue,BIAO Ya-ning,LI Yi-shui,WANG Yang,BU Jie,ZHANG Yi-xin*   

  1. School of Pharmacy,Hebei University of Chinese Medicine,Application Technology Research Center of Traditional Chinese Medicine Prescription in University of Hebei Province,Shijiazhuang 050200,China

  • Online:2021-08-28 Published:2021-09-08
  • Supported by:


摘要:

本文通过运用网络药理学和分子对接技术探究越鞠丸治疗非酒精性脂肪肝病的主要活性成分及作用靶点,分析其治疗非酒精性脂肪肝病的分子机制。通过TCMSP数据库筛选越鞠丸中各味药物的化学成分信息及作用于人体的靶点,使用OMIM、GeneCards疾病数据库收集非酒精性脂肪肝病的疾病基因。将NAFLD靶点与预测药物靶点进行映射,获得越鞠丸治疗非酒精性脂肪肝的最终靶标。DAVID富集分析数据库进行GO功能和KEGG通路富集分析并结合文献对相关通路进行分析;Cytoscape 3.7.2平台构建“越鞠丸-成分-NAFLD靶点-通路”网络图,进行网络拓扑分析并制作“PPI蛋白互作图”;PyMOL、Auto DockTools 1.5.6、Discovery Studio 3.5软件将靶标蛋白与关键化合物的小分子进行对接,以验证其治疗作用。网络药理学分析发现越鞠丸中共有31个有效成分可用于治疗非酒精性脂肪肝病,涉及59个靶基因及26条信号通路。查阅文献分析预测到越鞠丸可以通过调控PI3K-Akt信号通路、cAMP信号通路、胰岛素抵抗等通路治疗非酒精性脂肪肝病。分子对接结果显示越鞠丸有效成分关键靶蛋白NOS3与8-isopentenyl-kaempferol、MAPK14与异鼠李素具有良好的结合性。综上所述,本研究通过网络药理学预测了越鞠丸治疗非酒精性脂肪病可能的药效物质基础及其作用机制,并使用分子对接技术进行验证,为进一步挖掘越鞠丸的药效成分和临床应用提供新思路。

关键词: 网络药理学, 分子对接, 越鞠丸, 非酒精脂肪肝病

Abstract:

In order to explore the possible mechanism of Yueju pills in the treatment of nonalcoholic fatty liver disease (NAFLD),the active components and potential targets of Yueju pills were screened by network pharmacology and molecular docking technology.TCMSP database was used to screen the chemical composition information of each drug in Yueju pills and its target on human body.NAFLD target information was obtained by combining OMIM and GeneCardsand disease databases.The NAFLD targets were mapped to the predicted Chinese medicines targets to obtain the final targets of Yueju pills for the treatment of NAFLD.The potential targets were analyzed by GO function enrichment analysis and KEGG pathway enrichment analysis with DAVID platform,and the related pathways were analyzed combined with literatures.The network diagram of "Yueju pills-components-NAFLD targets-pathways" was constructed on Cytoscape 3.7.2 platform,the network topology analysis was carried out,and made the "PPI proteins interaction diagram"was made.PyMoL,Auto Docktools1.5.6 and Discovery Studio3.5 softwares was used to dock the target proteins with the small molecules of the key compounds to verify its therapeutic effect.The 31 active compounds,26 signaling pathways and 59 targets of Yueju pills in the treatment of NAFLD were obtained through network pharmacology analysis,the KEGG and literature analysis showed that Yueju pills can play a role by regulating many related pathways,such as PI3K-Akt signaling pathway,cAMP signaling pathway,insulin resistance and so on.The molecular docking indicated that the key target protein NOS3 with 8-isopentenyl-kaempferol,and MAPK14 with isorhamnetin of YueJu pills had high binding energy.In summary,this study predicted the possible pharmacodynamic substance basis and action mechanism of Yueju pills in the treatment of NAFLD through network pharmacology,and verified it by molecular docking technology,which providing a new idea for further mining the pharmacodynamic components of Yueju pills and its clinical application.

Key words: network pharmacology, molecular docking, Yueju pills, nonalcoholic fatty liver disease

中图分类号:  R285