天然产物研究与开发 ›› 2021, Vol. 33 ›› Issue (4): 667-675.doi: 10.16333/j.1001-6880.2021.4.017

• 数据研究 • 上一篇    下一篇

基于网络药理学探讨溪黄草黄酮类成分对酒精性肝病的作用机制

钟景斌1,刘文彬2,王晖1*   

  1. 1广东药科大学中药学院;2广东药科大学生命科学与生物制药学院 广东省生物活性药物研究重点实验室,广州 510006
  • 出版日期:2021-04-28 发布日期:2021-05-10
  • 基金资助:
    广东省农村科技特派员项目(KTP20200178)

Study on the mechanism of flavonoids from Isodonis Lophanthoidis Herba on alcoholic liver disease based on network pharmacology

ZHONG Jing-bin1,LIU Wen-bin2,WANG Hui1*   

  1. 1School of Traditional Chinese Medicine,Guangdong Pharmaceutical University;2School of Life Sciences and Biopharmaceutics,Guangdong Pharmaceutical University & Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances,Guangzhou 510006,China

  • Online:2021-04-28 Published:2021-05-10

摘要: 基于网络药理学探讨溪黄草黄酮类成分对酒精性肝病(alcoholic liver disease,ALD)的作用机制。通过文献、PubChem、TCMSP、PharmMapper数据库收集成分及预测靶点,利用UniProt数据库规范靶点。再运用GeneCards数据库获取ALD疾病靶点,并经Venny2.1.0获得交集靶点。蛋白相互作用的PPI网络由STRING 数据库构建,接着通过DAVID数据库对交集靶点进行GO功能与KEGG通路富集分析。溪黄草黄酮类成分-靶点-通路的作用网络由Cytoscape3.7.0构建,最后对核心靶点进行分子对接验证。本文共收集溪黄草中12种黄酮类成分,这些成分涉及172个与ALD相关的靶点,筛选24个核心靶点。GO富集显示52条生物过程、24条细胞成分、16条分子功能,主要涉及转录调控、细胞凋亡调节、血管内皮生长因子、NF-κB调节、脂质稳态、DNA损伤凋亡等生物过程;KEGG富集27条通路,主要涉及PI3K/Akt信号、FoxO信号、P53信号等关键通路;分子对接显示HSP90AA1、VEGFA、CCND1核心靶点与活性成分有良好的结合效应。综上,本文揭示溪黄草黄酮类成分作用于多靶点,参与多通路的调控发挥治疗ALD的作用机制,为进一步验证溪黄草黄酮类成分治疗ALD的相关靶点及通路提供依据。


关键词: 网络药理学, 分子对接, 溪黄草黄酮, 酒精性肝病, 作用机制

Abstract:

To explore the mechanism of flavonoids of Isodonis Lophanthoidis Herba on alcoholic liver disease (ALD)based on network pharmacology.Ingredients were collected by literature,PubChem and TCMSP databases,and PharmMapper platform was used to predict targets of components,after that UniProt database was used to standardize targets names.Then the disease targets of ALD was obtained by GeneCards,and the intersection targets were obtained by Venny2.1.0.The protein interactions network was constructed by the STRING,then GO and KEGG pathway for intersection targets were analyzed through DAVID.The interactions network of flavonoids of Isodonis Lophanthoidis Herba-target-pathway was constructed by Cytoscape3.7.0,eventually molecular docking was used to verify core targets.In this paper,12 flavonoids from Isodonis Lophanthoidis Herba were collected,which involved 172 ALD-related targets and 24 core targets were screened.GO enrichment showed 52 biological processes,24 cellular components and 16 molecular functions,which mainly involved transcriptional regulation,apoptosis regulation,vascular endothelial growth factor,NF-κB regulation,lipid homeostasis,DNA damage and apoptosis and other biological processes.KEGG enriched 27 pathways,mainly involving key pathways such as PI3K/Akt signal,FoxO signal,p53 signal and so on.Molecular docking revealed that the core targets of HSP90AA1,VEGFA and CCND1 had good binding effect with active components.In summary,this paper indicates that flavonoids ofIsodonis Lophanthoidis Herba act on multiple targets,participate in the regulation of multiple pathways to exert the mechanism of treating ALD,which provides a basis for further verifying the related targets and pathways of flavonoids of Isodonis Lophanthoidis Herba in the treatment of ALD.

Key words: network pharmacology, molecular docking, flavonoids of Isodonis Lophanthoidis Herba, ALD, mechanism

中图分类号:  R285