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

JIANG Liyuan; DONG Xin; TIAN Yuxin; SONG Jianfeng; ZHAO Weiliang; HU Yingfei; LI Mengying; FENG Jingqian

Abstract：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-RAGE signaling pathway,EGFR signaling pathway and core genes such as AKT1,ALB,and TP53.