清热凉血方治疗寻常型银屑病作用机制的网络药理学研究

Mechanism of Qingre Liangxue Formula in the Treatment of Psoriasis Vulgaris Based on Network Pharmacology

目的探讨清热凉血方治疗寻常型银屑病的分子机制。方法通过本草组鉴数据库、中国知网、PubChem、Swiss Target Prediction、UniProt数据库检索清热凉血方的活性成分和靶点;通过GeneCards、Therapeutic Target Database、DrugBank、phramGKB、OMIM数据库检索疾病靶点;绘制维恩图,筛选方剂与疾病的共有靶点;利用STRING数据库构建蛋白相互作用(PPI)网络,利用Cytoscape3.9.1软件筛选方剂治疗疾病的核心靶点;利用Cytoscape 3.9.1软件构建药物-活性成分-共有靶点网络,筛选度中心性排名前10的主要活性成分,并结合文献预测关键成分;通过Metascape数据库和RStudio的clusterProfiler包对共有靶点分别进行基因本体论(GO)功能富集和京都基因与基因组百科全书(KEGG)通路富集分析,采用Cytoscape 3.9.1软件构建药物-活性成分-靶点-通路网络,选取与PPI网络共有的靶点,并结合相关文献,筛选关键靶点。利用AutoDock 1.5.7软件对关键成分和关键靶点进行分子对接验证。结果共获得80种活性成分及449个靶点、1122个疾病靶点、115个共有靶点。共获得MAPK1、RELA、JAK2等10个核心靶点。关键成分包括槲皮素、山柰酚、常春藤苷元、黄芩素。GO功能富集分析获得生物学过程1904条、细胞组分56条和分子功能155条,包括炎性反应、激素反应、脂质结合等;KEGG通路富集分析获得8条主要路径,包括PI3K-Akt、HIF-1、IL-17信号通路等。关键靶点包括IL-6、VEGFA、TNF、EGFR。分子对接结果证明4种关键成分与其相应关键靶点均有较好的结合活性(≤5 kJ/mol)。结论清热凉血方治疗寻常型银屑病具有多成分-多靶点-多通路的特点,其作用机制可能与免疫、氧化应激、能量代谢等有关。

Objective To investigate the molecular mechanism of Qingre Liangxue Formula in the treatment of psoriasis vulgaris.Methods The active ingredients and targets of Qingre Liangxue Formula were searched by the HERB,CNKI,PubChem,Swiss Target Prediction and UniProt databases.The disease targets were searched by the GeneCards,Therapeutic Target Database,DrugBank,phramGKB and OMIM databases.The Venn diagram was drawn to screen common targets between the formula and psoriasis vulgaris.A protein-protein interaction(PPI)network was constructed by the STRING database,and the core targets of Qingre Liangxue Formula in the treatment of psoriasis vulgaris were screened by the Cytoscape 3.9.1 software.A drug-active ingredient-common target network was constructed by the Cytoscape 3.9.1 software,the top 10 active ingredients with high degree centrality were screened,and key ingredients were predicted based on literature.Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on common targets by the Metascape database and RStudio clusterProfiler package,respectively;a drug-active ingredient-target-pathway network was constructed by the Cytoscape 3.9.1 software;the common targets in this network with the PPI network were selected,and key targets were screened based on relevant literature.The molecular docking on key ingredients and key targets were performed by the AutoDock 1.5.7 software.Results A total of 80 active ingredients and 449 targets,1122 disease targets and 115 common targets were obtained.A total of 10 core targets were obtained,including MAPK1,RELA,JAK2,etc.The key ingredients included quercetin,kaempferol,hederagenin and baicalein.GO functional enrichment analysis showed 1904 biological processes,56 cellular components,and 155 molecular functions,including inflammatory response,hormone response,lipid binding,etc;KEGG pathway enrichment analysis showed eight main pathways,including PI3K-Akt,HIF-1,IL-17 signaling pathways,etc.The key targets included IL-6,VEGFA,TNF,EGFR.The molecular docking showed that four key ingredients had good binding activity with their corresponding key targets(≤5 kJ/mol).Conclusion Qingre Liangxue Formula in the treatment of psoriasis vulgaris has the multi-ingredients,multi-targets,and multi-pathways characteristics,and its mechanism may be related to immunity,oxidative stress,energy metabolism,and other factors.