The antioxidant effects of quercetin metabolites on the prevention of high glucose-induced apoptosis of human umbilical vein endothelial cells.
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.
Chao
Chia-Lun
CL
Division of Cardiology, Department of Internal Medicine, Taoyuan General Hospital, Department of Health, The Executive Yuan, Taoyuan, Taiwan.
Hou
Yu-Chi
YC
Chao
Pei-Dawn Lee
PD
Weng
Ching-Sung
CS
Ho
Feng-Ming
FM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020719:Glucuronides / Q000494:pharmacology; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D020719:Glucuronides; D017382:Reactive Oxygen Species; D011794:Quercetin; D048670:MAP Kinase Kinase 4; D053148:Caspase 3; D005947:Glucose