基于网络药理学和分子对接探讨玉屏风散“异病同治”荨麻疹、过敏性哮喘的作用机制

Mechanism of Yupingfeng Powder for Urticaria and Allergic Asthma with "Treating Different Diseases with Same Method" Based on Network Pharmacology and Molecular Docking

目的:基于网络药理学和分子对接探讨玉屏风散对荨麻疹和过敏性哮喘异病同治的作用机制。方法:通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)检索玉屏风散组方中药黄芪、白术、防风的活性成分及相关靶点。通过GeneCards数据库和在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)检索疾病相关靶点,并取荨麻疹和过敏性哮喘的交集靶点。将玉屏风散活性成分靶点与荨麻疹和过敏性哮喘的交集靶点导入R4.0.0软件绘制Venn图,得到药物与疾病的共同作用靶点,即为玉屏风散治疗荨麻疹及过敏性哮喘的潜在靶点。使用Cytoscape3.8.0绘制“药物-活性成分-潜在靶点-疾病”交互网络图。利用String数据库绘制潜在靶点的蛋白相互作用(protein-protein interaction,PPI)网络,并使用Cytoscape3.9.0对PPI网络进行优化。利用R4.0.0软件对潜在靶点进行基因本体(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)信号通路富集分析。选择玉屏风散中度值排名靠前的活性成分与疾病的核心靶点进行分子对接。结果:在TCMSP数据库中检索到活性成分45个及相关靶点305个。在GeneCard数据库和OMIM数据库得到交集靶点386个。取玉屏风散靶点及荨麻疹和过敏性哮喘共同靶点绘制Venn图,得到玉屏风散治疗荨麻疹和过敏性哮喘的潜在靶点24个。“药物-活性成分-潜在靶点-疾病”交互网络图分析得出槲皮素、山柰酚、β-谷甾醇、汉黄芩素为核心成分。PPI网络分析发现白细胞介素-6(interleukin-6,IL-6)、血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)、表皮生长因子受体(epidermal growth factor receptor,EGFR)等为核心靶点。GO功能富集分析获得38个生物过程条目和43个分子功能条目;KEGG信号通路富集分析获得93条通路。分子对接发现,活性成分与核心靶点有较好的结合力。结论:玉屏风散对荨麻疹和过敏性哮喘的异病同治作用具有多成分、多靶点、多通路的特点。

Objective:Based on network pharmacology and molecular docking to explore the mechanism of Yupingfeng Powder in "treating different diseases with same method" for urticaria and allergic asthma.Methods:The traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP) was used to search for the active ingredients and related targets of Chinese medicines Huangqi(Radix Astragali seu Hedysari),Baizhu(Rhizoma Atractylodis Macrocephalae),and Fangfeng(Radix Saposhnikoviae) in Yupingfeng Powder.The disease related targets were searched through the GeneCards database and the online mendelian inheritance in man(OMIM) database,and the intersection targets of urticaria and allergic asthma were collected.Then import the active ingredient targets of Yupingfeng powder and the intersection targets of urticaria and allergic asthma into the R4.0.0 software to draw a Venn diagram,and obtain the intersection targets of the drug and the disease,which is the potential targets of Yupingfeng Powder in the treatment of urticaria and allergic asthma.Use Cytoscape 3.8.0 to draw the "drugs-active ingredients-potential targets-diseases" interaction network diagram.Then use the String database to draw the protein-protein interaction(PPI) network of potential targets,and the PPI network was optimized using Cytoscape 3.9.0.And R4.0.0 software was used to conduct gene ontology(GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) signaling pathway enrichment analysis for potential targets.Finally,the active ingredients with the highest degree value in Yupingfeng San were selected for molecular docking with the core target of the disease.Results:45 active ingredients and 305 related targets were retrieved from the TCMSP database.386 intersection targets were obtained in GeneCard database and OMIM database.Taking the targets of Yupingfeng Powder and the common targets of urticaria and allergic asthma to draw a Venn diagram,24 potential targets of Yupingfeng Powder for treating urticaria and allergic asthma was obtained.And the interactive network diagram analysis of "drugs-active ingredients-potential targets-diseases" suggests that quercetin,kaempferol,β-sitosterol,and wogonin are the core components.PPI network analysis found that interleukin-6(IL-6),vascular endothelial growth factor A(VEGFA),and epidermal growth factor receptor(EGFR) are the core targets.GO function enrichment analysis obtained 38 biological process items and 43 molecular function items.KEGG signaling pathway enrichment analysis obtained 93 pathways.And molecular docking found that the active ingredients have a better binding force with the targets.Conclusion:"Treating different diseases with same method" of Yupingfeng Powder has the characteristics of multi-component,multi-target,and multi-channel in urticaria and allergic asthma treatment.