Quercetin Attenuates Atherosclerosis via Modulating Apelin Signaling Pathway Based on Plasma Metabolomics

作     者：LIU Li-qun ZHANG Peng QI Ying-zi LI Hui JIANG Yue-hua YANG Chuan-hua LIU Li-qun;ZHANG Peng;QI Ying-zi;LI Hui;JIANG Yue-hua;YANG Chuan-hua

作者机构：The First Clinical Medical CollegeShandong University of Traditional Chinese MedicineJinan(250355)China College of Integrated Chinese and Western MedicineBinzhou Medical UniversityYantaiShandong Province(264000)China Health CollegeShandong University of Traditional Chinese MedicineJinan(250355)China Department of PharmacyRuijin HospitalSchool of MedicineShanghai Jiaotong UniversityShanghai(200050)China Central LaboratoryAffiliated Hospital of Shandong University of Traditional Chinese MedicineJinan(250014)China Department of CardiovascularAffiliated Hospital of Shandong University of Traditional Chinese MedicineJinan(250014)China 

出 版 物：《Chinese Journal of Integrative Medicine》 (中国结合医学杂志（英文版）)

年 卷 期：2023年第29卷第12期

页      面：1121-1132页

核心收录：

学科分类：1008[医学-中药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学] 

基　　金：Supported by Shandong Province'Taishan Scholar'Construction Project Funds (No.2018-35) 

主　　题：quercetin atherosclerosis plasma metabonomics apelin signaling pathway 

摘      要：Objective:To interpret the pharmacology of quercetin in treatment of atherosclerosis(AS).Methods:Fourteen apolipoprotein E-deficient(ApoE^(-/-))mice were divided into 2 groups by a random number table:an AS model(ApoE^(-/-))group and a quercetin treatment group(7 in each).Seven age-matched C57 mice were used as controls(n=7).Quercetin[20 mg/(kg·d)]was administered to the quercetin group intragastrically for 8 weeks for pharmacodynamic *** morphological observation,the distribution of CD11b,F4/80,sirtuin 1(Sirt1)and P21 was assayed by immunohistochemistry and immunofluorescence to evaluate macrophage infiltration and tissue ***-performance liquid chromatography/tandem mass spectrometry(UPLC-MSC/MS)was performed to study the pharmacology of quercetin against ***,simultaneous administration of an apelin receptor antagonist(ML221)with quercetin was conducted to verify the possible targets of *** proteins in apelin signaling pathway,such as angiotensin domain type 1 receptor-associated proteins(APJ),AMP-activated protein kinase(AMPK),peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α),tissue plasminogen activator(TPA),uncoupling protein 1(UCP1)and angiotensinⅡreceptor 1(AT1R),were assayed by Western ***:Quercetin administration decreased lipid deposition in arterial lumen and improved the morphology of ApoE^(-/-)aortas in *** decreased the densities of CD11b,F4/80 and P21 in the aorta and increased the level of serum apelin and the densities of APJ and Sirt1 in the aorta in ApoE^(-/-)mice(all P0.05).Plasma metabolite profiling identified 118 differential metabolites and showed that quercetin affected mainly glycerophospholipids and fatty *** analysis suggested that the apelin signaling pathway was one of the main *** treatment increased the protein expressions of APJ,AMPK,PGC-1α,TPA and UCP1,while decreased the AT1R level(all P0.05).After the apelin pathway was