天然产物研究与开发 ›› 2022, Vol. 34 ›› Issue (2): 294-304.doi: 10.16333/j.1001-6880.2022.2.015

• 数据研究 • 上一篇    下一篇

基于网络药理学的益母草治疗产后腹痛的潜在分子机制研究

杨  勇1,张乐乐2*,盛菲亚2,李  维2,陈加容3,邹  亮4,杨  林2*   

  1. 1成都大学药学院;2成都大学基础医学院,成都 610106;3成都大学附属医院药剂科,成都 610081;4成都大学食品与生物工程学院,成都 610106
  • 出版日期:2022-02-28 发布日期:2022-03-07
  • 基金资助:
    国家自然科学基金(81903846)

Potential molecular mechanisms of Yimucao in the treatment of postpartum abdominal pain based on network pharmacology

YANG Yong1,ZHANG Le-le2*,SHENG Fei-ya2,LI Wei2,CHEN Jia-rong3,ZOU Liang4,YANG Lin2*   

  1. 1College of Pharmacy,Chengdu University;2School of Basic Medical Sciences,Chengdu University,Chengdu 610106,China;3Department of Pharmacy,Affiliated Hospital of Chengdu University,Chengdu 610081,China;4School of Food and Bioengineering,Chengdu University, Chengdu 610106,China
  • Online:2022-02-28 Published:2022-03-07

摘要:

本文通过网络药理学方法探讨益母草治疗产后腹痛的潜在分子机制。首先根据TCMSP数据库和文献挖掘益母草的活性成分,在TCMSP、Swiss Target Prediction、Similarity ensemble approach平台上检索活性成分靶点,在OMIM、GeneCards上检索产后腹痛靶点,得到益母草-产后腹痛交集靶点。利用STRING数据库构建蛋白互作(PPI)网络,接着利用Cytoscape软件对PPI网络进行拓扑分析,并对拓扑分析筛选出的核心靶点进行基因本体论(Gene Ontology,GO)分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路分析。最后利用免疫组化实验验证益母草对流产大鼠模型子宫组织中PGF2αR、MMP9、TIMP1、VEGFA、VEGFR2蛋白表达水平的影响。最终得到益母草活性成分10种,与产后腹痛相关靶点144个;通过PPI网络分析筛选出118个靶点,进一步拓扑分析后得到98个节点;然后对这98个节点进行GO和KEGG注释。GO分析得到1 151个生物过程(BP)条目,97个细胞组成(CC)条目,122个分子功能(MF)条目;KEGG分析得到41条通路,主要涉及雌激素、PI3K-Akt、MAPK、HIF-1信号通路等。最后免疫组化实验证明益母草可显著抑制流产模型大鼠子宫组织中PGF2αR、MMP9蛋白上调和TIMP1、VEGFR2蛋白下调。本研究通过网络药理学和免疫组化实验验证,显示益母草治疗产后腹痛是多成分、多靶点、多途径相互作用的结果,为益母草的临床应用提供了一定的理论依据。

关键词: 网络药理学, 益母草, 产后腹痛, 作用机制

Abstract:

This study aims to predict potential targets and molecular mechanisms of Yimucao in the treatment of postpartum abdominal pain based on network pharmacology.At first,the active components of Yimucao were screened by TCMSP platform and literature mining,and then the potential targets of active components of Yimucao were screened by TCMSP platform,Swiss Target Prediction platform,Similarity ensemble approach;relevant targets of postpartum abdominal pain were obtained by OMIM database,GeneCards database.Finally,the overlap targets between the disease and drug were obtained.Then a protein-protein interaction (PPI) network and further network topology were constructed to retrieve the key targets of the interaction relationship between Yimucao and postpartum abdominal pain.Finally,the perform gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were applied to identify the involved mechanisms.Immunohistochemical experiments were carried out to verify the outcomes.Finally,10 kinds of active components,and 144 kinds of intersecting targets with postpartum abdominal pain were screened.Then 98 targets were retrieved by topological analysis,and further analyzed using GO and KEGG enrichment analysis.GO analysis yielded 1 151 entries for biological processes (BP),97 entries for cell composition (CC) and 122 entries for molecular function (MF);KEGG enrichment analysis identified 41 pathways,which mainly involved estrogen signaling pathway and PI3K-Akt signaling pathway and MAPK signaling pathway and HIF-1 signaling pathway.The results of immunohistochemical experiments showed that Yimucao could significantly inhibit the up-regulation of PGF2αR and MMP9 proteins and down-regulation of TIMP1 and VEGFR2 proteins in the uterine tissue on abortion rat model.Through network pharmacology and immunohistochemical experiments,we found that the therapeutical effect of Yimucao against postpartum abdominal pain is an intricate result of multi-components,multi-targets and multi-channel,which provides a theoretical basis for the clinical application of Yimucao.

Key words: network pharmacology, Yimucao, postpartum abdominal pain, mechanism

中图分类号:  R285