摘要
目的 结合网络药理学和分子对接技术探索消银颗粒治疗银屑病的分子机制。方法 通过TCMSP数据库筛选中药复方消银颗粒的活性成分及活性成分对应的靶点。在GEO数据库获得银屑病转录组数据(GSE13355),分析银屑病差异表达基因。通过TTD、Drugbank、Disgenet、Genecards数据库获取银屑病治疗靶点。然后对药物靶点、银屑病治疗靶点、银屑病差异基因取交集得到消银颗粒治疗银屑病的关键靶点。采用cluster Profiler包对关键靶点进行GO和KEGG富集分析,揭示关键靶点的生物学功能。将潜在靶点导入String数据库构建关键靶点的PPI网络。将获得的有效活性成分及作用靶点导入Cytoscape软件构建药物-活性成分-靶点网络。最后,采用分子对接技术对有效成分和靶点进行验证。结果 共筛选出消银颗粒的活性成分198种,包括槲皮素、木犀草素、山柰酚、汉黄芩素等。将鉴定出的4408个银屑病治疗靶点,635个差异表达及254个活性成分相关靶点取交集得到24个消银颗粒治疗银屑病的关键靶点。关键靶点主要富集在TNF信号通路、IL-17信号通路。PPI分析结果显示FOS、IL-1B、MMP-9及CCL-2位于网络核心。最后,分子对接表明FOS、IL-1B、MMP-9及CCL-2能与消银颗粒主要活性成分槲皮素稳定结合。结论 消银颗粒治疗银屑病可能通过多成分、多靶点、多通路,发挥抗炎、促进角质形成细胞凋亡、抑制炎性因子趋化作用治疗银屑病。
Objective To explore the molecular mechanism of Xiaoyin granules in the treatment of psoriasis based on network pharmacology and molecular docking technology. Methods We obtained the active ingredients of Xiaoyin granules from the Traditional Chinese Medicine Systems Pharmacology(TCSMP)database,whose relatied targets were identified from the TCSMP.The transcriptome data of psoriasis(GSE13355) were obtained from GEO database to analyze the differentially expressed genes in psoriasis. TTD,Drugbank,Disgenet and Genecards database were used to collect the genes associated with psoriasis. The intersected genes of targets of active compounds,genes associated with psoriasis and differentially expressed genes between psoriasis and normal samples were then identified as treatment targets Xiaoyin granule in the treatment of psoriasis. The clusterProfiler package was applied to perform Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis to reveal the biological functions of key targets of psoriasis. Import potential targets into String database,then the protein-protein interaction network of psoriasis targets was analyzed by String database. Moreover,a herbs-active compounds-psoriasis targets network was built by Cytoscape.Additionally,Autodock Vina was applied to perform molecular docking analysis to verify the effective components and targets. Results A total of 194 active ingredients were selected and 254 targets were identified after deleting duplicates in both databases. 635 DEGs were identified between the psoriasis patients and controls. According to the above results,24 targets for the treatment of psoriasis were screened,which significantly enriched in TNF signal pathway and IL-17 signaling pathway. Among them,FOS,IL-1B,MMP-9 and CCL-2 were screened as hub genes in the PPI network. Molecular docking analysis suggested that FOS,IL-1B,MMP-9 and CCL-2 formed stably bind to quercetin, the main active component of Xiaoyin granule,respectively. Conclusion Compound Xiaoyin Granules may throu
作者
鲁有望
董荣静
石年
陈用军
LU Youwang;DONG Rongjing;SHI Nian;CHEN Yong-jun(Dermatology Department of Huangshi Central Hospital/Affiliated Hospital of Hubei Institute of Technology,Huangshi,Hubei 435000,Hubei Province;Medical College of Hubei Institute of Technology,Huangshi,Hubei 435000)
出处
《皮肤病与性病》
2022年第6期427-435,共9页
Dermatology and Venereology
基金
湖北理工学院人才引进项目(21xjz33R、21xjz34R)。
