NATURAL PRODUCT RESEARCH AND DEVELOPMENT ›› 2021, Vol. 33 ›› Issue (3): 479-489. doi: 10.16333/j.1001-6880.2021.3.016

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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

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

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