University of Hull logo

The dietary flavonol quercetin ameliorates angiotensin II-induced redox signaling imbalance in a human umbilical vein endothelial cell model of endothelial dysfunction via ablation of p47ᵖʰᵒˣ expression

Jones, Huw S.; Gordon, Andrew; Magwenzi, Simba G.; Naseem, Khalid; Atkin, Stephen L.; Courts, Fraser L.


Andrew Gordon

Khalid Naseem

Fraser L. Courts

Simba G. Magwenzi

Stephen L. Atkin


Scope: Quercetin is reported to reduce blood pressure in hypertensive but not normotensive humans, but the role of endothelial redox signaling in this phenomenon has not been assessed. This study investigated the effects of physiologically obtainable quercetin concentrations in a human primary cell model of endothelial dysfunction in order to elucidate the mechanism of action of its antihypertensive effects. Methods and results: Angiotensin II (100 nM, 8 h) induced dysfunction, characterized by suppressed nitric oxide availability (85 ± 4% p < 0.05) and increased superoxide production (136 ± 5 %, p < 0.001). These effects were ablated by an NADPH oxidase inhibitor. Quercetin (3 μM, 8 h) prevented angiotensin II induced changes in nitric oxide and superoxide levels, but no effect upon nitric oxide or superoxide in control cells. The NADPH oxidase subunit p47 phox was increased at the mRNA and protein levels in angiotensin II-treated cells (130 ± 14% of control, p < 0.05), which was ablated by quercetin co-treatment. Protein kinase C activity was increased after angiotensin II treatment (136 ± 51%), however this was unaffected by quercetin co-treatment. Conclusion: Physiologically obtainable quercetin concentrations are capable of ameliorating angiotensin II-induced endothelial nitric oxide and superoxide imbalance via protein kinase C-independent restoration of p47 phox gene and protein expression. Quercetin restores key cellular signaling molecules (nitric oxide and superoxide) to normal levels in a model of vascular endothelial cell dysfunction.  This is achieved by restoring the levels of p47 phox (a key component in the superoxide generating machinery NADPH oxidase) to normal levels.  The assessment of the modulation of these pathways by quercetin concentrations similar to those measured in human blood is a major part of the novelty of this work.

Journal Article Type Article
Publication Date 2016-04
Journal Molecular nutrition and food research
Print ISSN 1613-4125
Electronic ISSN 1613-4133
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 60
Issue 4
Pages 787-797
Keywords Quercetin; Nitric oxide; Superoxide; Endothelial cells; NADPH oxidase
Publisher URL
Additional Information Authors' accepted manuscript of article published in: Molecular nutrition and food research, 2016, v.60, issue 4.


You might also like

Downloadable Citations