为研究迷迭香酸缓解食物过敏的效应机制,利用网络药理学和分子对接以及脂质组学探究迷迭香酸(Rosmarinic acid,RA)缓解食物过敏的效应机制.利用数据库分析平台(TCMSP)、Swiss Target Prediction、Pharm Mapper、Super Pred和Gene Cards等获得RA的潜在效应靶点.通过软件Cytoscape和String数据库构建"活性成分-靶点"蛋白互作(PPI)网络,并采用AutoDockTools软件进行分子对接验证.进一步通过建立卵清蛋白(Ovalbumin,OVA)食物过敏小鼠模型验证RA缓解食物过敏的效应,并基于高分辨质谱对小鼠血清进行脂质代谢分析.结果表明,网络药理分析共筛选到关联靶点46个.基因本体(Geno ontology,GO)富集分析表明RA主要通过对蛋白质磷酸化、鞘糖脂、磷脂和类固醇等的结合发挥作用.京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析表明关联靶点主要富集在Th1和Th2细胞分化通路、脂代谢和炎症性肠病通路等.动物实验结果显示RA干预可以显著(P＜0.05,P＜0.01,P＜0.001)抑制OVA致敏引起的小鼠血清过敏反应介质上升,且RA干预组小鼠血清总胆固醇(Total Cholesterol,T-CHO)和甘油三酯(Triglyceride,TG)水平下降.脂质组学分析中,在正/负离子模式下分别筛选出25/36种潜在差异脂质代谢物.对脂质差异代谢物的富集分析表明,小鼠的血清脂质代谢影响甘油磷脂代谢和鞘脂代谢通路.因此,本研究表明RA主要通过调节脂质代谢和机体炎症反应发挥缓解食物过敏的作用.
Abstract
To investigate the mechanism of rosmarinic acid in alleviating food allergy,an integrated approach,involving network pharmacology,molecular docking and lipid-omics were employed to investigate the potential mechanism of rosmarinic acid(RA)in alleviating food allergy.To obtain potential therapeutic targets for RA,database analysis platform such as database and analysis platform(TCMSP),Swiss Target Prediction,Pharm Mapper,Super Pred and Gene Cards were employed.The"active ingredient-target"protein-protein(PPI)network was constructed using Cytoscape software and the String database.The validation of molecular docking was performed using AutoDockTools software.Furthermore,a food allergy mouse model using ovalbumin(OVA)and lipid metabolism studies on mouse serum based on high-resolution mass spectrometry were applied to investigate the antiallergic effect of RA and the underling mechanism.Results showed that,through the network pharmacology analysis,a total of 46 associated target proteins were identified.The geno ontology(GO)enrichment analysis of the target proteins indicated that RA primarily exerted its effects through modula-tion of protein phosphorylation and the binding between glycosphingolipids,phospholipids and steroids.The kyoto encyclopedia of genes and genomes(KEGG)analysis indicated that the associated targets were mainly enriched in the Thl/Th2 cell differentiation pathways,lipid metabolism and inflammatory bowel disease pathways.The results indicated that RA intervention could significantly suppress the elevation of allergic mediators in the serum of mice sensitizes with OVA.In addition,the RA intervention group showed a decrease in the levels of total cholesterol and triglycerides in the mouse serum.In lipidomics analysis,25 and 36 differentially expressed lipid metabolites were screened in positive and negative ion modes,respectively.Enrichment analysis of the differentially expressed lipid metabolites indicated that the serum lipid metabolism in mice affected glycerophospholipid metabolism and sphingolipid metabolic pathways.Therefore,this study demonstrated that RA primarily exerted its alleviating effect on food allergies by regulating lipid metabolism and the body's inflammatory response.
维普
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