Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 68, Issue 39, Pages 10875-10883Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.0c03907
Keywords
quercetin; NADPH oxidase; HO-1; endothelial dysfunction; atherosclerosis
Funding
- National Natural Science Foundation of China [31960196, 31760255, 31560255]
- Natural Science Foundation of Jiangxi province [20171BCB23041, 20161BAB215215]
- Graduate Innovation Fund Project of Jiangxi Normal University [YJS2019015]
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NADPH oxidase-dependent superoxide (O-2(-)) production and oxidative stress play important roles in endothelial dysfunction and atherosclerosis. Herein, we investigated the potential effects of dietary quercetin, a flavonoid derived in the diet from vegetables and fruit, on vascular endothelial function and atherosclerosis in the high-fat diet (HFD)-fed apolipoprotein E-deficient (ApoE(-/-)) mice. Dietary quercetin treatment significantly suppressed endothelial dysfunction and aortic atherosclerosis in HFD-fed ApoE(-/-) mice (P < 0.05, all cases). Mechanistic studies demonstrated that dietary quercetin significantly attenuated p47phox expression and inhibited NADPH oxidase-derived oxidative stress in the aortas of HFD-fed ApoE(-/-) mice, while the expression and activity of antioxidant enzyme heme oxygenase-1 (HO-1) was enhanced after quercetin treatment (P < 0.05, all cases). In vitro, it was found that quercetin significantly attenuated NADPH oxidase-derived O-2- formation (75 +/- 5.6% for quercetin versus 100 +/- 6.0% for the control group, P < 0.01) in endothelial cells through induction of HO-1. In addition, the favorable effects of quercetin on oxidant (i.e., H2O2 )-induced endothelial dysfunction could be eliminated by tin protoporphyrin IX (an HO-1 inhibitor) or HO1-specific siRNA. Our results demonstrated the critical roles of NADPH oxidase and HO-1 for the indirect antioxidant properties of quercetin in vascular diseases.
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