天然产物研究与开发 ›› 2021, Vol. 33 ›› Issue (3): 479-489.doi: 10.16333/j.1001-6880.2021.3.016

• 数据研究 • 上一篇    下一篇

基于网络药理学及分子对接探讨雷公藤干预结缔组织相关间质性肺病的分子机制

张希涛1,葛春蕾1,彭井华1,贾新华2*   

  1. 1山东中医药大学,济南 250014;2山东中医药大学附属医院,济南 250011
  • 出版日期:2021-03-28 发布日期:2021-04-01
  • 基金资助:
    国家中医药管理局“全国中医药创新骨干人才培训项目”(国中医药人教函[2019]128号);“泰山学者”建设工程专项经费资助(ts201712096)

Study on the molecular mechanism of Tripterygium wilfordii in the treatment of connective tissue disease-associated interstitial lung disease based on network pharmacology and molecular docking

ZHANG Xi-tao1,GE Chun-lei1,PENG Jing-hua1,JIA Xin-hua2*   

  1. 1Shandong University of Traditional Chinese Medicine,Jinan 250014,China; 2Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250011,China

  • Online:2021-03-28 Published:2021-04-01

摘要:

为探究雷公藤干预结缔组织相关间质性肺疾病(CTD-ILD)的分子机制。运用网络药理学的方法,通过TCMSP数据库挖掘雷公藤的主要化学成分及作用靶点,利用Genecards、OMIM、DrugBank数据库获取CTD-ILD相关靶点,利用String平台进行蛋白质相互作用分析,构建PPI网络并挖掘网络中潜在的蛋白质功能模块,然后采用Metascape进行GO及KEGG富集分析,利用Cytoscape3.8.0软件构建“雷公藤成分-CTD-ILD-信号通路”网络,最后通过AutoDock Vina进行分子对接。通过分析得到雷公藤干预CTD-ILD的靶点共80个,核心成分为山奈酚、雷公藤内酯醇、川陈皮素、β-谷甾醇等,核心靶点有PTGS2、JUN、MAPK8、RELA、SCN5A、TNF等。GO和KEGG富集分析显示,IL17信号通路、Toll样受体信号通路、TNF信号通路、HIF-1信号通路、FoxO信号通路、Cancer信号通路等为雷公藤干预CTD-ILD的主要通路,涉及炎症,氧化应激,细胞凋亡及癌症等多个生物过程。分子对接结果亦显示,分子亲和力小于-7 kcal/mol占总数的62.5%,其中5次化合物的预测值超过原配体。综上,本研究初步揭示了雷公藤通过多成分、多靶点、多通路作用机制干预CTD-ILD的分子机制,并经分子对接予以验证,为临床应用雷公藤治疗CTD-ILD提供了理论依据。

关键词: 雷公藤, CTD-ILD, 网络药理学, 分子对接

Abstract:

To explore the molecular mechanism of Tripterygium wilfordii intervention in connective tissue-related interstitial lung disease (CTD-ILD).Applying the methods of network pharmacology.First,the main chemical components and targets of T. wilfordii  were mined by TCMSP database,Using gencards,OMIM and DrugBank database to obtain the related targets of CTD-ILD,using String platform to analyze protein interaction,constructing PPI network and mining potential protein function modules in the network.Go and KEGG enrichment analysis was carried out on Metascape platform,and then a network of "T. wilfordii component CTD-ILD signal pathway" was constructed with the software of Cycloscape 3.8.0.Finally,molecular docking was carried out through autodockvina.Through the analysis,80 targets of T. wilfordii intervention in CTD-ILD were obtained.The core components were kaempferol,triptolide,kaempferin,β-sitosterol and so on.The core targets were PTGS2,Jun,mapk8,rela,SCN5A,TNF and so on.The enrichment analysis of go and KEGG showed that IL17 signaling pathway,toll like receptor signaling pathway,TNF signaling pathway,HIF-1 signaling pathway,FOXO signaling pathway and cancer signaling pathway were the main pathways for T. wilfordii to intervene CTD-ILD,involving multiple biological processes such as inflammation,oxidative stress,apoptosis and cancer.The results of molecular docking also showed that the molecular affinity was less than -7 kcal/mol,accounting for 62.5% of the total,and the predicted value of five compounds was higher than that of the original ligands.To sum up,this study preliminarily revealed the mechanism of T. wilfordii intervention in CTD-ILD with multi-component,multi-target and multi-channel,provided theoretical basis for clinical application of T. wilfordii intervention in CTD-ILD,and verified by molecular docking.

Key words: Tripterygium wilfordii, CTD-ILD, network pharmacology, molecular docking

中图分类号:  R285