机构地区:[1]北京中医药大学东方医院,北京100078 [2]北京中医药大学东直门医院通州院区,北京101100 [3]大兴区妇幼保健院,北京102600
出 处:《世界中医药》2023年第16期2289-2297,共9页World Chinese Medicine
基 金:国家重点研发计划资助项目(2018YFC1704101);第六批国家老中医药专家学术经验继承项目(20170615)。
摘 要:目的:基于网络药理学方法分析苍耳子散治疗季节性变应性鼻炎的作用机制,为经典方剂临床拓展运用及疗效评价提供参考。方法:通过中药系统药理学数据库与分析平台(TCMSP)获取苍耳子、辛夷、白芷、川芎的主要化学成分及其靶点,根据毒药物动力学(ADME)筛选中药活性组分,并应用网络图像化软件CytoScape 3.7.2构建苍耳子散活性成分及作用靶点网络;通过人类基因信息数据库(GeneCards)获取季节性变应性鼻炎相关靶点;应用CytoScape 3.7.2构建蛋白质-蛋白质相互作用(PPI)网络,将网络提取的关键靶点提交至STRING 11.0数据库,分析其参与的生物过程。将药物靶点与疾病靶点取交集基因后,利用注释、可视化和富集分子功能数据库(DAVID)进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,构建“成分-靶点-通路”网络。通过构建卵清蛋白(VOA)大鼠变应性鼻炎模型对筛选的靶点应用酶联免疫吸附试验(ELISA)进行验证。结果:苍耳子散治疗季节性变应性鼻炎的核心的活性成分为柚皮苷、谷甾醇、木犀草素等,核心靶点有前列腺素内过氧化物合酶(PTGS)2、磷脂酰肌醇-3激酶γ催化亚基(PIK3CG)、PTGS1、蛋白激酶B(AKT)1、肿瘤坏死因子(TNF)、β2-肾上腺素受体(ADRB2)、表皮生长因子受体(EGFR)、白细胞介素-1β(IL-1β)等。苍耳子散治疗季节性变应性鼻炎的生物学通路主要作用于钙信号通路、缺氧诱导因子-1(HIF-1)信号通路、Toll样受体信号通路、TNF信号通路等,其功能主要为调节炎症反应及免疫相关细胞因子的表达等。动物实验结果显示,与正常对照组比较,模型对照组大鼠血清IgE、IL-4、PTGS2、PTGS1、AKT1 mRNA表达均显著上调(P<0.01),同时γ干扰素(IFN-γ)mRNA表达显著下调(P<0.01);与模型对照组比较,苍耳子散组大鼠血清IgE、IL-4、PTGS2、PTGS1、AKT1 mRNA表达显著下调(P<0.01),同时IFN-γ mRObjective:The study aims to analyze the action mechanism of Cangerzi Powder in the treatment of seasonal allergic rhinitis based on network pharmacology and provide references for the clinical expansion of the classic prescriptions and the evaluation of the efficacy.Methods:The main chemical components and targets of Fructus Xanthii,Flos Magnoliae,Radix Angelicae Dahuricae,and Rhizoma Ligustici Chuanxiong were obtained from the traditional Chinese medicines systems pharmacology platform(TCMSP),and the active components of traditional Chinese medicine were screened according to absorption,distribution,metabolism,and excretion(ADME).The network imaging software Cytoscape 3.7.2 was used to analyze the active components and target networks of Cangerzi Powder.Corresponding targets of seasonal allergic rhinitis were obtained through the Gencards database.Cytoscape 3.7.2 was utilized to construct a protein-protein interaction(PPI)network,and the key targets extracted from the network were submitted to the STRING11.0 database to analyze the biological processes involved.After taking the intersection genes of drug targets and disease targets,the database for annotation,visualization,and integrated discovery(DAVID database)was used to perform gene ontology(GO)enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis,and the“component-target-pathway”network was built.The screened targets were verified by enzyme-linked immunosorbent assay(ELISA)by constructing an ovalbumin(VOA)rat model of allergic rhinitis.Results:The core active components of Cangerzi Powder in the treatment of seasonal allergic rhinitis were naringin,stigmasterol,luteolin,etc.The core targets were PTGS2,PIK3CG,PTGS1,AKT1,TNF,ADRB2,EGFR,IL-1β,etc.The biological pathway of Cangerzi Powder in the treatment of seasonal allergic rhinitis mainly acted on the calcium signaling pathway,HIF-1 signaling pathway,Toll-like receptor signaling pathway,TNF signaling pathway,etc.Its function was mainly to regulate the expressio
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