基于网络药理学和分子对接技术探讨雷公藤治疗关节病型银屑病的作用机制

Mechanism of Tripterygium Wilfordii in the Treatment of Psoriatic Arthritis Based on Network Pharmacology and Molecular Docking

目的 基于网络药理学和分子对接的方法,研究雷公藤治疗关节病型银屑病的作用机制。方法 计算机检索中药系统药理学分析平台(TCMSP)获取中药雷公藤的活性成分和对应靶点;应用GeneCards、Online Mendelian Inheritance in Man(OMIM)、DrugBank数据库检索关节病型银屑病的疾病靶点,利用Venn软件获取药物与疾病共同靶点;采用Cytoscape3.7.2软件构建活性成分-靶点网络图;采用STRING数据库和Cytoscape3.7.2软件对交集靶点构建蛋白互作网络图(PPI)进行分析;应用DAVID蛋白数据库进行基因本体(GO)功能和京都基因与基因组数据库(KEGG)通路富集分析;最后采用AutoDock1.5.6软件对核心靶点及核心成分进行对接验证。结果 在中药雷公藤中获取了51个活性成分,414个有效作用靶点,疾病获取1 393个靶点,药物疾病共同靶点70个。PPI中有11个关键靶点包括信号转导和转录活化因子3(STAT3)、肿瘤坏死因子(TNF)和二聚体转录因子(JUN)等。GO功能富集发现356个条目,KEGG通路富集分析作用通路105个,主要涉及癌症的途径、TNF信号通路、磷脂酰肌醇3-激酶/蛋白激酶B(PI3K-Akt)信号通路、Toll样受体(TLR)信号通路等。分子对接验证显示核心靶点与核心活性成分有较强结合活性。结论 初步揭示了雷公藤治疗关节病型银屑病多成分、多靶点、多途径的作用机制,有助于为进一步研究提供依据。

Objective Inorder to study the mechanism of Tripterygium wilfordii in the treatment of arthritis psoriasis based on the methods of network pharmacology and molecular docking.Methods The active ingredients and corresponding targets of Tripterygium wilfordii were obtained through Traditional Chinese medicine systems phannacology(TCMSP).GeneCards,Online Mendelian Inheritance in Man(OMIM),and DrugBank databases were used to search for disease targets of arthropathic psoriasis,and Venn software were used to obtain common targets for drugs and diseases.The active ingredient-target network diagram was constructed through Cytoscape 3.7.2;the String database and Cytoscape 3.7.2 were used to construct a protein-protein interaction network(PPI)analysis of the intersection targets.The Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed through the application of DAVID database;finally,Autodock 1.5.6 was used to verify the core target and core components.Results In the TCM Tripterygium wilfordii,51 active ingredients,414 effective targets,1393 targets for diseases,and 70 common targets for drug diseases were obtained.There were 11 key targets in the PPI network including signal transducer and activator of transcription 3(STAT3),tumor necrosis factor(TNF),dimer transcription factor(JUN),etc.GO function enrichment found 356 entries,KEGG pathway enrichment analysis of 105 pathways,which mainly involved cancer pathways,TNF signaling pathways,PI3K-Akt signaling pathways,Toll-like receptor(TLR)signaling pathways,etc.Molecular docking verification showed that the core target had a strong binding activity with the core active ingredients.Conclusion This study initially reveal the multi-component,multitarget,and multi-path mechanism of Tripterygium wilfordii in the treatment of articular psoriasis,providing basis for further research.