网络药理学探索雷公藤治疗口腔扁平苔藓的药理特性和治疗机制

Prediction of the pharmacological characteristics and therapeutic mechanism of Tripterygium wilfordii in treat⁃ing oral lichen planus based on network pharmacology

目的基于网络药理学方法研究雷公藤治疗口腔扁平苔藓(oral lichenplanus,OLP)的主要活性成分及其潜在的药理特性和作用机制。方法基于中药系统药理学分析平台等获取雷公藤化学成分及靶点,Gene Cards等数据库获取OLP靶点,将药物与疾病靶点进行韦恩分析,得到雷公藤治疗OLP的潜在靶点。采用Cytoscape 3.7.2构建化学成分⁃靶点网络,STRING构建蛋白质⁃蛋白质相互作用网络,Network Analyzer计算网络拓扑属性,利用Cluster Profiler软件包进行GO、KEGG富集分析,并构建雷公藤化学成分⁃靶点⁃通路网络。结果获得雷公藤23个成分和150个靶点,OLP靶点472个,交集靶点44个。雷公藤治疗OLP的核心活性成分有雷公藤内酯、山奈酚、川陈皮素等,关键靶点包括肿瘤坏死因子、丝氨酸/苏氨酸蛋白激酶1等。GO富集分析得到白细胞分化、对脂多糖的反应等63个GO条目。KEGG富集分析得到TNF信号通路、IL17信号通路等111条通路。结论应用网络药理学方法初步揭示雷公藤治疗OLP的主要成分、作用靶点和作用途径,为将来从雷公藤中开发出高活性、低毒性的治疗OLP的药物的深入研究提供了理论依据。

Objective To explore the potential mechanism of the main active component Tripterygium wilfordii in the treatment of oral lichen planus based on network pharmacology.Methods The components of Tripterygium wil⁃fordii and targets were searched through the Traditional Chinese Medicine system pharmacology database and analysis platform(TCMSP)and the Traditional Chinese Medicine integrated database(TCMID)databases.The related targets of oral lichen planus(OLP)were obtained through databases such as Gene Cards.The OLP targets were mapped by Venn analysis to the targets of Tripterygium wilfordii to screen out the common targets as the treatment of OLP targets of Tripterygium wilfordii.The Cytoscape software and STRING were used to construct a chemical component⁃target net⁃work and protein⁃protein interaction network,a network analyzer was used to compute the network topology properties,a cluster profiler software was used to analyze the GO classification enrichment analysis and KEGG signal path analy⁃sis,and a Tripterygium wilfordii chemical components⁃targets⁃pathway network diagram was constructed.Results Twenty⁃three components and 44 OLP treatmenttargets of Tripterygium wilfordii were obtained.The key active ingredi⁃ents of Tripterygium wilfordii in the treatment of OLP are triptolide,kaempferol,and tangerine peel.The key targets in⁃clude TNF and AKT1.The GO classification enrichment analysis obtained 63 GO terms,which are mainly involved in the leukocyte differentiation and reaction to lipopolysaccharides.The KEGG analysis identified 111 signaling pathways,which are mainly related to the TNF signaling pathway and IL17 signaling pathway.Conclusion Based on the network pharmacology,this study preliminarily revealed themain components,targets and pathways of Tripterygium wilfordii in the treatment of OLP.This study can provide a theoretical basis for further research to explore drugs with high activity and low toxicity to treat OLP from Tripterygium wilfordii.