基于网络药理学及分子对接技术探讨玉屏风散治疗慢性荨麻疹的作用机制

Mechanism of Yupingfeng San in Treatment of Chronic Urticaria Based on Network Pharmacology and Molecular Docking Technology

目的基于网络药理学和分子对接技术探讨玉屏风散治疗慢性荨麻疹(CU)的作用机制。方法通过中药系统药理学分析平台(TCMSP)筛选玉屏风散的活性化合物和靶点,利用GeneCards数据库以“Chronic urticaria”为关键词检索提取疾病靶点,通过Venn图筛选化合物和疾病的共同靶点。使用Cytoscape 3.7.2软件构建“药物-共同靶点-疾病”网络,通过构建蛋白互作网络(PPI),查找共同靶点之间的相互作用。对共同靶点进行GO功能富集分析及KEGG通路富集分析。依据AutoDock软件将主要活性化合物与主要靶点蛋白受体进行分子对接分析,使用PyMol软件将结果可视化。结果TCMSP数据库显示,玉屏风散三味药物共有44个活性化合物和102个靶点;GeneCards数据库显示,共有960个靶点与CU密切相关,两数据集相互映射共获得35个交集靶点。GO功能富集分析提示,交集靶点共涉及395个参与条目,其生物过程主要富集于对抗生素的反应、细胞对异物的反应、对金属离子的反应、G蛋白偶联乙酰胆碱受体信号通路、对糖皮质激素的反应等。KEGG通路富集分析提示,交集靶点共涉及95条信号通路,主要涵盖前列腺肿瘤、卡波西肉瘤相关疱疹病毒感染、在糖尿病并发症中的晚期糖基化终产物(AGE)-晚期糖基化终产物受体(RAGE)信号通路、磷脂酰肌醇-3激酶(PI3K)-蛋白激酶B(Akt)信号通路、抗药性等。分子对接结果显示,主要化合物与主要靶点之间有较好的结合力。结论玉屏风散通过多成分、多靶点,调节免疫功能、缓解炎性反应治疗CU。

Objective In order to investigate the mechanism of Yupingfeng San in treatment of chronic urticaria(CU)based on network pharmacology and molecular docking technology.Methods Active compounds and targets related to the traditional Chinese medicine(TCM)herbs were searched through the traditional Chinese medicine systems phannacology(TCMSP)database and analysis platform.Through Online Mendelian Inheritance in Man(OMIM),GeneCards,PharmGkb and Therapeutic Target Database(TTD)database searched for relevant targets of CU.The common targets of compounds and diseases were screened by Venn graphs.Cytoscape 3.7.2 software was used to construct the"drug-common target-disease"network,and the interaction between common targets was found by constructing the Protein-Protein Interaction Network(PPI).Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on the common targets.AutoDock was used to perform molecular docking analysis of core active compounds and core target protein receptors,and PyMol was used to visualize the results.Results TCMSP database indicated that there were 44 active compounds and 102 targets of Yupingfeng San.GeneCards database indicated that there were 960 targets closely related to CU,and 35 intersection targets were obtained by mapping between the two data sets.GO analysis function of enrichment,intersection targets involved 395 entries to participate in,its biological process mainly occurred in response to the antibiotic,cellular response toxenobiotic,response to metal ion,G protein-coupledreceptor signaling pathway, response to glucocorticoid. KEGG pathway enrichment analysis suggests that intersection targetsinvolved 95 signaling pathways,mainly covers the prostate cancer,kaposi sarcoma-associated herpesvirus infection,advancedglycation endproduct (AGE) - receptor of advanced glycation endproduct (RAGE) signal pathway in diabetic complications,phosphatidylinositol 3-kinase (PI3K) - protein kinase B (AKT) signaling pathway,platinum drug resistance,etc. The resultsof molecular docking showed that there was a good binding force between the main compounds and the main targets. Conclusion From the perspective of bioinformatics analysis,it is clear that Yupingfeng San treats CU through multiple componentsand multiple targets to regulate immune function and relieve inflammation.