基于网络药理学及分子对接探讨当归饮子治疗慢性自发性荨麻疹的作用机制

Mechanism of Danggui Yinzi Decoction in Treating Chronic Spontaneous Urticaria based on Network Pharmacological and Molecular Docking Technology

目的使用网络药理学方法及分子对接技术探究当归饮子治疗慢性自发性荨麻疹(CSU)多成分-多靶点-多通路的作用机制。方法通过TCMSP数据库、BATMAN-TCM数据库、GeneCards数据库及OMIM数据库获取当归饮子的主要活性成分、作用靶点以及CSU疾病相关靶点。通过CytoScape软件和String数据库构建药物-活性成分-靶点-疾病网络和蛋白质-蛋白质相互作用(PPI)网络,借助DAVID数据库对药物-疾病共同靶点进行基因功能和通路富集分析,以AutoDock-Vina软件实现核心靶点与关键成分的分子对接。结果从当归饮子中筛选得到138个活性成分,涉及CSU疾病靶点120个,得到基因功能和通路富集分析结果共709条,分子对接结果显示核心靶点与关键成分结合活性较好。结论黄酮类化合物是当归饮子治疗CSU的主要有效成分,可能通过干预CSU中炎性反应、血管通透性、氧化应激和自身免疫等生物过程,调节肿瘤坏死因子(TNF)信号通路、磷脂酰肌醇3-激酶-蛋白激酶B(PI3K-Akt)信号通路和缺氧诱导因子-1(HIF-1)信号通路等来发挥治疗CSU的作用。

Objective In order to explore the mechanism of Danggui Yinzi decoction on the multi-component,multi-target and multi-pathway of chronic spontaneous urticaria(CSU)by network pharmacology and molecular docking technology.Methods The main active components of Danggui Yinzi decoction and their targets were obtained through traditional Chinese medicine systems pharmacology(TCMSP),Bioinformatics Analysis Tool for Molecular mechanism of traditional Chinese medicine(BATMAN-TCM)and literature search.GeneCards database and online mendelian inheritance in man(OMIM)were used to select the disease targets of CSU.CytoScape software and String database were used to construct the drug-component-target-disease network and the protein-protein interaction network(PPI).Gene function and pathway enrichment involved in the targets were analyzed by the database for annotation,visualization and integrated discovery(DAVID).AutoDock-Vina software was used to verify the molecular docking of core targets and active components.Results Totally 138 active ingredients and 120 CSU related targets were screened in Danggui Yinzi decoction.All of 709 related results of gene function and pathway enrichment analysis were obtained.The results of molecular docking showed that the active components had good binding activity with core targets.Conclusion Flavonoids are the main effective components of Danggui Yinzi decoction in the treatment of CSU,which may play a role in the treatment of CSU by interfering with inflammation,vascular permeability,oxidative stress and autoimmunity,tumor necrosis factor(TNF)signaling pathways,phosphatidylinositol 3-kinase-Akt(PI3K-Akt)signaling pathways and hypoxia inducible factor-1(HIF-1)signaling pathways and so on.