基于网络药理学及分子对接探讨青风藤治疗痛风性关节炎的作用机制

Mechanism of Sinomenii Caulis in treatment of gout arthritis based on network pharmacology and molecular docking

目的基于网络药理学及分子对接技术探讨青风藤治疗痛风性关节炎的作用机制。方法运用中药系统药理学数据库与分析平台(TCMSP),获取青风藤的活性成分,并通过SwissTarget Prediction数据库预测其靶点。使用GeneCards、OMIM、DisGenet、TTD数据库获取与痛风性关节炎相关的靶点,通过维恩图找到两者的共同靶点,并将其输入STRING平台和Cytoscape 3.9.1构建蛋白质相互作用(PPI)网络图。利用DAVID数据库对共同靶点进行基因本体(GO)生物学富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。借助AutoDockTools分子对接和可视化处理。结果获得青风藤6种有效活性成分,药物与疾病靶点交集后获得84个关键靶点,PPI显示核心靶点有前列腺素内过氧化物合酶2(PTGS2)、过氧化物酶体增殖物激活受体G(PPARG)、转录因子AP-1(JUN)、Toll样受体4(TLR4)、一氧化氮合酶2(NOS2)等。KEGG通路分析,可能涉及了癌症通路、肿瘤坏死因子(TNF)、Th17细胞分化、核因子κB(NF-κB)通路、脂质和动脉粥样硬化通路等。分子对接结果显示,青风藤的主要活性成分青藤碱、β-谷甾醇、拉兹马宁碱、乌心石环氧内脂、千金藤啶碱与关键蛋白PPARG、NOS2、PTGS2、TLR4表现出良好的结合能力。结论青风藤具有多成分、多靶点特性,通过多途径来缓解炎症反应,对治疗痛风急性关节炎的发作具有潜在的疗效。

Objective To explore the mechanism of Sinomenii Caulis in treating gouty arthritis based on network pharmacology and molecular docking techniques.Methods To obtain the effective active ingredients of Sinomenii Caulis and predict their targets through the TCMSP and SwissTarget Prediction database.Gouty arthritis related targets were obtained from GeneCards,OMIM,DisGenet,and TTD databases.The intersection targets of both sets were identified using a Venn diagram,and these were input into the STRING platform and Cytoscape 3.9.1 to construct a PPI network.The common targets were subjected to GO biological enrichment analysis and KEGG pathway enrichment analysis using the DAVID database.Molecular docking and visualization processing were performed using AutoDockTools.Results Six effective active ingredients of Sinomenii Caulis were obtained.After the intersection of drug and disease targets,84 key targets were identified.The PPI network revealed core targets including PTGS2,PPARG,JUN,TLR4,NOS2,etc.KEGG pathway analysis suggested involvement in cancer pathways,TNF signaling,Th17 cell differentiation,NFκB pathway,lipid metabolism,and atherosclerosis pathways,among others.Molecular docking results demonstrated favorable binding capabilities of Sinomenii Caulis main active components sinomenine,β-sitosterol,16-epi-isositsirikine,michelenolide,stepholidine with key proteins PPARG,NOS2,PTGS2,and TLR4.Conclusion Sinomenii Caulis exhibits a multi-component,multi-target characteristic,alleviating inflammation through multiple pathways,indicating potential efficacy in treating acute attacks of gouty arthritis.