Document Detail


The antioxidant effects of quercetin metabolites on the prevention of high glucose-induced apoptosis of human umbilical vein endothelial cells.
MedLine Citation:
PMID:  19007452     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Diabetes mellitus is an important risk factor for CVD. A previous study showed that high glucose induced the apoptosis of human umbilical vein endothelial cells (HUVEC) via the sequential activation of reactive oxygen species, Jun N-terminal kinase (JNK) and caspase-3. The apoptosis cascade could be blocked by ascorbic acid at the micromolar concentration (100 microm). In addition to ascorbic acid, quercetin, the most abundant dietary flavonol, has been recently actively studied in vascular protection effects due to its antioxidant effect at low micromolar concentrations (10-50 microm). Quercetin sulfate/glucuronide, the metabolite of quercetin in blood, however, has been rarely evaluated. In the present study, we investigated the effect of quercetin sulfate/glucuronide on the prevention of high glucose-induced apoptosis of HUVEC. HUVEC were treated with media containing high glucose (33 mm) in the presence or absence of ascorbic acid (100 microm) or quercetin sulfate/glucuronide (100 nm, 300 nm and 1 microm). For the detection of apoptosis, a cell death detection ELISA assay was used. The level of intracellular H2O2 was measured by flow cytometry. JNK and caspase-3 were evaluated by a kinase activity assay and Western blot analysis. The results showed that high glucose-induced apoptosis was inhibited by quercetin sulfate/glucuronide in a dose-dependent manner. The effect of quercetin sulfate/glucuronide on H2O2 quenching, inhibition of JNK and caspase-3 activity at the nanomolar concentration (300 nm) was similar to that of ascorbic acid at the micromolar concentration (100 microm). The findings of the present study may shed light on the pharmacological application of quercetin in CVD.
Authors:
Chia-Lun Chao; Yu-Chi Hou; Pei-Dawn Lee Chao; Ching-Sung Weng; Feng-Ming Ho
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-11-14
Journal Detail:
Title:  The British journal of nutrition     Volume:  101     ISSN:  1475-2662     ISO Abbreviation:  Br. J. Nutr.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-16     Completed Date:  2009-07-08     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0372547     Medline TA:  Br J Nutr     Country:  England    
Other Details:
Languages:  eng     Pagination:  1165-70     Citation Subset:  IM    
Affiliation:
Division of Cardiology, Department of Internal Medicine, Taoyuan General Hospital, Department of Health, The Executive Yuan, Taoyuan, Taiwan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*
Caspase 3 / metabolism
Cells, Cultured
Dose-Response Relationship, Drug
Endothelial Cells / drug effects,  metabolism
Endothelium, Vascular / cytology,  drug effects*,  metabolism
Glucose / antagonists & inhibitors,  pharmacology*
Glucuronides / pharmacology
Humans
MAP Kinase Kinase 4 / metabolism
Quercetin / pharmacology*
Rats
Reactive Oxygen Species / metabolism
Umbilical Veins / cytology,  drug effects*,  metabolism
Chemical
Reg. No./Substance:
0/Glucuronides; 0/Reactive Oxygen Species; 117-39-5/Quercetin; 50-99-7/Glucose; EC 2.7.12.2/MAP Kinase Kinase 4; EC 3.4.22.-/Caspase 3

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