基于HPLC-Q-Exactive Orbitrap MS/MS整合网络药理学研究衢枳壳降糖的物质基础及作用机制  

Study on the Material Basis and Mechanism of Quzhiqiao's Hypoglycemic Effect Based on HPLC-Q-Exactive Orbitrap MS/MS Integrated Network Pharmacology

作　　者：姜莉苑[1] 董馨 田雨欣 宋剑锋 赵维良 胡颖菲[1] 李梦盈 冯敬骞[1] JIANG Liyuan;DONG Xin;TIAN Yuxin;SONG Jianfeng;ZHAO Weiliang;HU Yingfei;LI Mengying;FENG Jingqian(Quzhou College of Technology,Quzhou 324000,China;Department of Pharmacy,Inner Mongolia Medical University,Hohhot 010110,China;Quzhou Institute for Food and Drug Control,Quzhou 324000,China;Zhejiang Institute for Food and Drug Control,Hangzhou 310052,China)

机构地区：[1]衢州职业技术学院,浙江衢州324000 [2]内蒙古医科大学药学院,呼和浩特010110 [3]衢州市食品药品检验研究院,浙江衢州324000 [4]浙江省食品药品检验研究院,杭州310052

出　　处：《中国中医基础医学杂志》2024年第3期461-467,共7页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：浙江省高等学校国内访问工程师校企合作项目(FG2023217);衢州市重点科技攻关项目(2023K245);衢州市指导性科技攻关项目(2021051);衢州市重点创新团队资助项目(衢委人才〔2020〕3号)。

摘　　要：目的以入血成分为研究对象,基于网络药理学探究衢枳壳对糖尿病起效的物质基础及作用机制。方法采用高效液相色谱串联四极杆-静电场轨道阱高分辨质谱(high-performance liquid chromatography tandem quadrupole-electrostatic field orbitrap high resolution mass spectrometry,HPLC-Q-Exactive Orbitrap MS/MS)对衢枳壳入血成分进行鉴定,在此基础上通过Swiss Target Prediction与SuperPred数据库预测入血成分作用靶点,同时在OMIM,GeneCards等数据库获取糖尿病靶点。采用Cytoscape 3.9.1绘制中药衢枳壳“活性成分-靶点-疾病”网络关系图,利用String数据分析平台进行蛋白互作(protein-protein interaction,PPI)网络分析,筛选关键靶点。通过DAVID数据库对关键靶点进行基因本体功能(gene ontology,GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。应用Autodock 1.5.7软件进行分子对接验证。结果共鉴定衢枳壳入血成分20个,筛选出潜在靶点170个,核心靶点32个。GO功能富集和KEGG信号通路分析结果显示缺氧诱导因子(hypoxia-inducible factor,HIF)-1信号通路、晚期糖基化终末产物(advanced glycation end products,AGE)-晚期糖基化终产物受体(receptor for advanced glycation end products,RAGE)信号通路、表皮生长因子(epidermal growth factor receptor,EGFR)信号通路、癌症蛋白聚糖通路等为衢枳壳降糖的关键通路,丝氨酸/苏氨酸蛋白激酶(RAC serine/threonine-protein kinase,AKT)1、白蛋白(albumin,ALB)、细胞肿瘤抗原p53(cellular tumor antigenp 53,TP53)、肿瘤坏死因子(tumor necrosis factor,TNF)、EGFR为其中关键靶点,且衢枳壳中5个活性成分与核心靶点经分子对接后的结合活性较好。结论衢枳壳中的芦丁、新橙皮苷、橙皮苷、芸香柚皮苷、川陈皮素等可能为衢枳壳降糖的物质基础,可能是通过调控HIF-1、AGE-RAGE、EGFR等信号通路及AKT1、ALB、TP53等核心基因发挥降糖作�Objective Taking blood-absorbed components as the research object,the material basis and mechanism of Quzhiqiao in the treatment of diabetes were clarified by network pharmacology.Methods High-performance liquid chromatography tandem quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(HPLC-Q-Exactive Orbitrap MS/MS)was used to identify the blood components of Quzhiqiao.On this basis,the target prediction of the blood-entering components was obtained from the Swiss Target Prediction and SuperPred database,and the target related to diabetes was acquired from OMIM,GeneCards,and other disease databases.The network model of"components-targets-diseases"of Quzhiqiao population was established by Cytoscape 3.9.1 software.The PPI network was constructed by the String data analysis platform for screening out the core targets.The DAVID database was used for gene ontology(GO)enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of the core targets.Molecular docking analysis was conducted by Autodock 1.5.7 software.Results A total of 20 blood-absorbed ingredients were identified,while 170 potential targets and 32 core targets were screened.The results of GO function annotation and KEGG signaling pathway analysis showed that hypoxia-inducible factor(HIF)-1 signaling pathway,advanced glycation end products(AGE)-receptor for advanced glycation end products(RAGE)signaling pathway,epidermal growth factor receptor(EGFR)signaling pathway and cancer proteoglican pathway were the key pathways of Quzhiqiao among which RAC serine/threonine-protein kinase(AKT)1,albumin(ALB),cellular tumor antigenp 53(TP53),tumor necrosis factor(TNF),EGFR were the key targets.In addition,molecular docking showed that the five active ingredients of Quzhiqiao had robust binding abilities with the core targets.Conclusion Rutin,neohesperidin,hesperidin,narirutin,and nobiletin might be the hypoglycemic substances of Quzhiqiao,which may play a role in regulating the HIF-1 signaling pathway,AGE

关 键 词：衢枳壳 糖尿病 网络药理学 物质基础 作用机制 

分 类 号：R966[医药卫生—药理学]