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Quercetin Attenuates Atherosclerosis via Modulating apelin signaling pathway Based on Plasma Metabolomics

Chinese Journal of Integrative Medicine 2023年第12期29卷 1121-1132页

作者： LIU Li-qun ZHANG Peng QI Ying-zi LI Hui JIANG Yue-hua YANG Chuan-hua The First Clinical Medical College Shandong University of Traditional Chinese MedicineJinan(250355)China College of Integrated Chinese and Western Medicine Binzhou Medical UniversityYantaiShandong Province(264000)China Health College Shandong University of Traditional Chinese MedicineJinan(250355)China Department of Pharmacy Ruijin HospitalSchool of MedicineShanghai Jiaotong UniversityShanghai(200050)China Central Laboratory Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan(250014)China Department of Cardiovascular Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan(250014)China

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 evaluation.Besides 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 senescence.Ultra-performance liquid chromatography/tandem mass spectrometry(UPLC-MSC/MS)was performed to study the pharmacology of quercetin against AS.Then,simultaneous administration of an apelin receptor antagonist(ML221)with quercetin was conducted to verify the possible targets of quercetin.Key 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 blot.Results:Quercetin administration decreased lipid deposition in arterial lumen and improved the morphology of ApoE^(-/-)aortas in vivo.Quercetin 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 Papelin signaling pathway was one of the main pathways.Quercetin treatment increased the protein expressions of APJ,AMPK,PGC-1α,TPA and UCP1,while decreased the AT1R level(all Papelin pathway was blocked by ML221,the effect of quercetin was aba

关键词： quercetin atherosclerosis plasma metabonomics apelin signaling pathway

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