基于网络药理学研究麻芥方抗过敏性鼻炎的潜在生物学机制及初步验证

Mechanism of Majie Decoction against allergic rhinitis based on network pharmacology and preliminary verification

目的基于网络药理学研究麻芥方治疗过敏性鼻炎的潜在生物学机制,并通过小鼠体内实验进行初步验证。方法利用中药系统药理学数据库和分析平台(TCMSP)数据库,筛选麻芥方中符合口服利用率、药物相似性阈值的有效成分组,并得到成分所对应的靶点,构建活性成分-靶点相互作用网络。采用Digsee数据库搜集过敏性鼻炎相关靶点,分析2个靶点数据集,找到连接活性成分和过敏性鼻炎的交集靶点。运用String数据库分析交集靶点的蛋白质-蛋白质相互作用关系及其参与的KEGG/Reactome信号通路。通过动物实验对IL-4信号通路进行了验证。结果筛选出了麻芥方53个具有入血潜力的活性成分(新黄芩素、榄核莲黄酮等),34个抗过敏性鼻炎靶点(雌激素受体、雄激素受体、过氧化物酶体增殖物激活受体、前列腺素内过氧化物合酶2、二肽基肽酶4等)。分析发现麻芥方的抗过敏性鼻炎相关靶点显著富集于多条炎症因子相关信号通路中。验证结果表明麻芥方能够降低过敏性鼻炎小鼠血清组胺、IgE及IL-4的水平。结论麻芥方抗过敏性鼻炎的主要生物学机制可能与调控多种炎症因子信号通路,尤其是IL-4和IL-13信号通路有关。

Objective To study the mechanism of Majie Decoction(Ephedra and White Mustard Seed Decoction)against allergic rhinitis based on network pharmacology and preliminarily verify it through in vivo experiments in mice.Methods Effective constituents of Majie Decoction(Ephedra and White Mustard Seed Decoction)were selected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP database)based on threshold of oral availability(OB)and drug-likeness(DL).Then corresponding targets of the selected constituents were obtained to form an effective constituents-targets network Targets relevant to allergic rhinitis were achieved based on Digsee database.The intersection dataset of these datasets was analyzed.Then the protein-protein reaction and its effect on the KEGG/Reactome pathway were analyzed based on String database.IL-4 signal pathway were verified by mouse model.Results 53 unduplicated effective constituents,including neobaicalein,panicolin,and 34 important targets against allergic rhinitis,including ESR1,AR,PPARG,PTGS2,DPP4,were obtained.The protein interaction network and enrichment analyses showed that targets of Majie Decoction(Ephedra and White Mustard Seed Decoction)are enriched in various inflammatory factor-related pathways.Animal experiments showed that Majie Decoction(Ephedra and White Mustard Seed Decoction)significantly reduced the levels of serum IgE,histamine and IL-4 in mice with allergic rhinitis.Conclusion The main mechanism of Majie Decoction(Ephedra and White Mustard Seed Decoction)may be relevant to regulation of multiple inflammatory factor-related pathways,especially IL-4 and IL-13.