UPLC-Q-Exactive Orbitrap MS/MS结合网络药理学探讨复方截敏汤治疗儿童过敏性鼻炎药效物质基础及作用机制

Pharmacodynamic material basis and mechanism of Compound Jiemin Decoction for the treatment of allergic rhinitis in children based on UPLC-Q-Exactive Orbitrap MS/MS and network pharmacology

关键词:  复方截敏汤  UPLC-Q-Exactive Orbitrap MS/MS  网络药理学  作用机制  过敏性鼻炎  

Key words:  Compound Jiemin Decoction  UPLC-Q-Exactive Orbitrap MS/MS  network pharmacology  molecular mechanism  allergic rhinitis  

摘要:

目的 采用血清药物化学与网络药理学探究复方截敏汤（Compound Jiemin Decoction, JMD）治疗儿童过敏性鼻炎（allergic rhinitis，AR）的药效物质基础及作用机制。方法 利用UPLC-Q-Exactive Orbitrap MS/MS技术，结合BiotreeDB V3.0数据库及对照品比对，鉴定JMD入血成分；通过网络药理学构建蛋白-蛋白互作网络，结合“药物-成分-靶点-疾病”分析、GO功能分析、KEGG富集分析和分子对接技术，揭示JMD治疗儿童AR的关键活性成分及潜在作用机制。结果 JMD提取物中共鉴定出115种化合物，其中75种成分可在血清中溯源。网络药理学结果显示JMD治疗儿童AR的潜在靶点176个，其可能通过戈米辛A、α-亚麻酸、香叶木素、光甘草定、杨梅素等活性成分作用于TNF、IL6、GAPDH、AKT1、STAT3等核心靶点，调控Th17细胞分化、HIF-1、PI3K/AKT、TNF、NF-κB等信号通路发挥疗效。结论 JMD通过多成分协同、多靶点作用及多通路调控发挥治疗AR作用，研究结果为后续药理机制的深度剖析及临床实践应用提供了科学支撑。

Abstract:

OBJECTIVE To investigate the pharmacological basis and mechanism of action of Compound Jiemin Decoction (JMD) in the treatment of allergic rhinitis (AR) in children using a combination of serum medicinal chemistry and network pharmacology. METHODS The blood components of JMD were identified by UPLC-Q-Exactive Orbitrap MS/MS, combined with BiotreeDB V3.0 database and control comparison. The protein-protein interaction network was constructed by network pharmacology, combined with the ‘drug-component-target-disease’ analysis, GO functional analysis, KEGG enrichment analysis and molecular docking techniques to reveal the key active components and potential mechanism of action of JMD in the treatment of AR in children. RESULTS A total of 115 compounds were identified in the JMD extracts, of which 75 components were found in serum. The results of the network pharmacological research showed that JMD has 176 potential targets for the treatment of AR in children, which may act on the core targets such as TNF, IL6, GAPDH, AKT1, STAT3, and regulate Th17 cell differentiation, HIF-1, PI3K/AKT other signaling pathways to exert the therapeutic effect through the active ingredients such as gomisin A, linolenic acid, diosmetin, glabridin and myricetin. CONCLUSION JMD exerts therapeutic effects on AR through multi-component synergy, multi-target action and multi-pathway regulation, and the results of this study provide scientific support for the subsequent in-depth analysis of pharmacological mechanisms and application in clinical practice.