基于网络药理学和分子对接分析雷公藤治疗银屑病的作用机制

Effect mechanism of Tripterygium wilfordii in treatment of psoriasis based on network pharmacology and molecular docking

本文将探讨基于网络药理学研究雷公藤治疗银屑病的作用机制。在GeneCards数据库中收集银屑病相关靶点,在中药系统药理学数据库与分析平台(TCMSP)数据库中筛选雷公藤的活性成分及其作用靶点,并利用PubChem数据库确认活性成分的化学式。将能确认化学式的活性成分对应的蛋白质靶点与银屑病相关的蛋白质靶点进行匹配取交集,确定雷公藤中与银屑病相关的活性成分及靶点。利用生物信息分析软件Cytoscape 3.8.0进行雷公藤活性成分-银屑病作用靶点网络构建。通过STRING平台构建蛋白质相互作用(protein-protein interaction,PPI)网络,通过生物信息学资源数据库DAVID在线分析工具进行基因本体(GO)以及京都基因和基因组百科全书(KEGG)富集分析。最终从雷公藤中筛选出与银屑病相关的主要活性成分21个,对应89个银屑病相关靶点。PPI网络构建结果筛选出相互作用的核心靶蛋白共33个。KEGG富集分析结果显示:雷公藤活性成分作用的银屑病靶点主要涉及肿瘤坏死因子(TNF)信号通路、PI3K-Akt信号通路、HIF-1信号通路、Toll样受体信号通路。分子对接结果显示,山萘酚、雷公藤甲素、β-谷甾醇、穿陈皮素与PTGS2之间具有较强结合性。本研究通过网络药理学研究了雷公藤治疗银屑病的主要活性成分及其对应的靶点和作用通路,为雷公藤治疗银屑病提供了新思路。

Based on network pharmacology,the mechanism of treatment of psoriasis by Tripterygium wilfordii was studied.The related targets of psoriasis were collected in the GeneCards database.The active ingredients and potential target genes of Tripterygium wilfordii were screened out in the TCMSP database,and the chemical formulas of the active ingredients were confirmed in the PubChem database.Then,the targets of psoriasis and Tripterygium wilfordii were intersected and aggregated to obtain the active ingredients and action targets related to psoriasis in Tripterygium wilfordii.The network diagram was constructed by using Cytoscape3.8.0 software,the protein interaction network was constructed by using STRING database,GO and KEGG analysis were analyzed with DAVID online analysis tool.Finally,21 main active ingredients related to psoriasis were screened from Tripterygium wilfordii,corresponding to 89 psoriasis-related targets.Kaempferol,Triptolide,β-sitosterol and Nobiletin were ingredients with most targets related to psoriasis.PTGS1,PTGS2,ADRA1B,NCOA1,PDE3A,OPRM1,RXRA were targets that closely related to psoriasis of Tripterygium wilfordii.The results of PPI network construction showed that there were 33 interacting core target proteins,including JUN,STAT3,RELA,AKT1,TNF,TP53,etc.KEGG enrichment analysis showed that the psoriatic targets of Tripterygium wilfordii active ingredients mainly related to TNF signal pathway,PI3K-Akt signal pathway,HIF-1 signal pathway and Toll like receptor signal pathway.The results of molecular docking showed that Kaempferol,Triptolide,beta-Sitosterol and Nobiletin successfully docked with PTGS2.Using the method of network pharmacology,the main active ingredients,target points and related pathways of Tripterygium wilfordii in the treatment of psoriasis are initially revealed,which provides a new idea for Tripterygium wilfordii to treat psoriasis.