苍耳子治疗变应性鼻炎的网络药理学分析及作用机制研究  

Network pharmacology and mechanism of Xanthii Fructus for allergic rhinitis

作　　者：李丹[1] 章秀梅 宣自华[1] 刘丛彬[1] 俞年军[1,2,3] 谢冬梅 LI Dan;ZHANG Xiu-mei;XUAN Zi-hua;LIU Cong-bin;YU Nian-jun;XIE Dong-mei(Anhui University of Chinese Medicine,Hefei 230012;Institute of Traditional Chinese Medicine Resources Protection and Development,Hefei 230012;Anhui Key Laboratory of Research&Development of Chinese Medicine,Hefei 230012)

机构地区：[1]安徽中医药大学,合肥230012 [2]安徽省中医药科学院中药资源保护与开发研究所,合肥230012 [3]中药研究与开发安徽省重点实验室,合肥230012

出　　处：《中南药学》2022年第5期1010-1016,共7页Central South Pharmacy

基　　金：国家自然科学基金项目(No.81503190);安徽中医药大学2021年度校级探索性科研项目(No.2021hxts22)。

摘　　要：目的通过网络药理学分析苍耳子治疗变应性鼻炎(AR)的机制,并通过动物学实验进行药效部位筛选及治疗活性研究。方法①应用Cytoscape软件,通过TCMSP、GeneCards、Uniprot数据库构建“活性成分-靶点-疾病”网络;通过STRING数据库构建蛋白互作网络,推测核心靶点;使用Metascape数据库对靶点进行GO、KEGG富集分析。②建立大鼠AR模型,以血清中的免疫球蛋白E(IgE)、白介素-4(IL-4)和干扰素(IFN-γ)的含量为评价指标,比较苍耳子不同提取物治疗大鼠AR的效果;采用Western blot法检测各组大鼠鼻黏膜组织中的PI3K和P-AKT蛋白表达。结果①本研究纳入活性成分19个,预测靶点217个,疾病靶点2803个,PPI筛选核心靶点108个;GO生物功能分析发现:存在神经元迁移、积极调控细胞迁移、对受伤的反应、对脂多糖的反应等生物过程,膜筏、膜面、细胞外基质等细胞组成,蛋白酶活性、细胞因子受体结合、蛋白质结构域特异性结合等分子功能;KEGG信号通路分析发现,乙型肝炎、PI3K-Akt信号通路、MAPK信号通路、T细胞受体信号通路、Th17细胞分化、细胞周期等通路参与调控。②动物大鼠实验表明苍耳子总水提物及正丁醇部位可改善鼻黏膜病理变化,降低AR大鼠血清IgE和IL-4水平(P<0.01),升高IFN-γ水平(P<0.01);AR模型大鼠鼻黏膜组织中PI3K和P-AKT蛋白表达增加。给予药物治疗干预后,各给药组PI3K、P-AKT蛋白表达下调且苍耳子正丁醇组作用最为显著。结论通过网络药理学和动物实验发现苍耳子可能通过调控PI3K/AKT通路发挥其治疗作用,为更深入研究苍耳子治疗AR提供了依据。Objective To determine the mechanism of Xanthii Fructus for allergic rhinitis(AR)by network pharmacology,and verify it with animal experiments.Methods①Cytoscape software was used to construct an active component-target-disease network through TCMSP,GeneCards and Uniprot databases.The protein interaction network was established with the STRING database,and the core targets were speculated.GO and KEGG enrichment analysis was performed on the targets with Metascape database.②Rats were intraperitoneal injected with ovalbumin and aluminum hydroxide suspension,and local nasal stimulation of aluminum hydroxide drops was used to establish AR model to determine the anti-inflammatory activity of Xanthii Fructus.The contents of immunoglobulin E(IgE),interleukin-4(IL-4)and interferon(IFN-γ)in the serum of the rats were used as the evaluation indexes.PI3K and P-AKT protein expressions in the nasal mucosa of rats in each group were detected by Western blot.Results①This study included 19 active ingredients,217 predicted targets,2803 disease targets,and 108 PPI screening core targets.GO biological function analysis found:t biological processes such as neuronal migration,active regulation of cell migration,response to injury and response to lipopolysaccharide;cell components such as membrane raft,membrane surface,extracellular matrix and other;molecular functions such as protease activity,cytokine receptor binding,protein domain specific binding and other.KEGG signaling pathway analysis showed that hepatitis B,PI3K-Akt signaling pathway,MAPK signaling pathway,T cell receptor signaling pathway,Th17 cell differentiation,cell cycle and other pathways were involved in the regulation.②Rat experiments showed that the total water extract of Xanthii Fructus and n-butanol fractions improved the pathological changes in the nasal mucosa,reduced the levels of serum IgE and IL-4 in AR rats(P<0.01),and increased the level of IFN-γ(P<0.01);The expression of PI3K and P-AKT proteins increased in the nasal mucosa of AR model rats.After t

关 键 词：苍耳子 变应性鼻炎 网络药理学 活性部位 PI3K/AKT通路 

分 类 号：R285[医药卫生—中药学]