基于网络药理学分析荆芥—防风药对的分子作用机制

Molecular Mechanism of Couplet Medicinals Jingjie‐Fangfeng Based on Network Pharmacology

目的:基于网络药理学,探讨“荆芥-防风”药对的功效物质基础和配伍药理机制。方法:采用网络药理学方法,利用网络数据库检索荆芥-防风药对中的化学成分及其作用靶点;利用STRING平台构建蛋白互作网络(protein protein interaction,PPI),依据度值和介数挑选关键靶蛋白;利用DAVID数据库对关键靶基因进行基因本体(gene ontology,GO)生物过程富集和聚类分析,并对靶点的京都基因和基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)信号通路进行分析。结果:通过口服利用度(oral bioavailability,OB)和类药性(drug-likeness,DL)条件筛选出27个荆芥-防风药对活性化合物,相应作用靶点208个,PPI网络包含118个靶点。GO富集分析包含GO条目377个,其中生物过程相关条目305个,分子功能相关条目27个,细胞组分相关条目45个,KEGG通路富集分析包含KEGG条目84条。结论:荆芥-防风药对的有效化合物成分可能通过调控抑癌基因TP53(tumor protein p53,TP53)、AKT1、肿瘤坏死因子(tumor necrosis factor,TNF)、血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)、白细胞介素6(interleukin-6,IL-6)、细胞周期素D1(G1/S-specific cyclin-D1,CCND1)及周期表依赖性激酶因子1A(cyclin-dependent kinase inhibitor 1,CDKN1A)等靶点,使基因功能富集于肿瘤细胞信号通路、病毒感染、病毒致癌信号通路和PI3K-Akt、p53信号通路等通路,从而清除外邪侵达到祛风解表的目的。

Objective:To explore the material basis of efficacy and compatibility mechanism of"Jingjie(herba schizonepetae)-Fangfeng(saposhnikovia divaricata)"based on network pharmacology.Methods:Network pharmacology was used in the study,the chemical ingredients and its action targets of the couplet medicinals were searched in network database;PPI was constructed by using STRING platform,the key target proteins were selected according to the degree value and intermediate number;GO biological process enrichment and cluster analysis of key target genes were carried out by using DAVID database,and KEGG signaling pathway of the targets was analyzed.Results:All 27 active compounds from Jingjie‐Fangfeng were screened by OB and DL condition,208 corresponding targets and PPI network contains 118 targets.GO enrichment analysis contained 377 GO items,among them,there were 305 biological process related items and 27 molecular function related items,45 cellular component related items,enrichment analysis of KEGG pathway embodied 84 KEGG items.Conclusion:effective ingredients of Jingjie-Fangfeng may regulate tumor suppressor genes TP53,AKT1,TNF,VEGFA,IL-6,CCND1,CDKN1A and other targets,the gene functions are enriched in tumor cell signaling pathway,virus infection,virus carcinogenic signaling pathway,PI3K-Akt,p53 signaling pathway and others,therefore,the couplet medicinals could develop the effects of dispelling wind and relieving the exterior by eliminating the tissue and cells infected by external pathogen invading human body.