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Molecules 2016, 21(8), 1009; doi:10.3390/molecules21081009

Effects on Nitric Oxide Production of Urolithins, Gut-Derived Ellagitannin Metabolites, in Human Aortic Endothelial Cells

1
Endocrinology and Metabolism, Department of Clinical and Experimental Medicine, University of Parma, Parma 43126, Italy
2
The Laboratory of Phytochemicals in Physiology, Department of Food Science, University of Parma, Parma 43125, Italy
3
Division of Endocrinology, Azienda Ospedaliero-Universitaria of Parma, Parma 43126, Italy
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Rafael Llorach
Received: 13 June 2016 / Revised: 19 July 2016 / Accepted: 29 July 2016 / Published: 2 August 2016
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Abstract

The consumption of foodstuffs yielding circulating compounds able to maintain endothelial function by improving nitric oxide (NO) bioavailability can be considered as an effective strategy for cardiovascular disease prevention. This work assessed the in vitro effects of urolithin A, urolithin B, and urolithin B-glucuronide, ellagitannin-derived metabolites of colonic origin, on NO release and endothelial NO synthase (eNOS) activation in primary human aortic endothelial cells (HAECs). Urolithins were tested both individually at 15 μM and as a mixture of 5 μM each, at different time points. The biotransformation of these molecules in cell media due to cell metabolism was also evaluated by UHPLC-MSn. The mix of urolithins at 5 μM significantly increased nitrite/nitrate levels following 24 h of incubation, while single urolithins at 15 μM did not modify NO bioavailability. Both the mix of urolithins at 5 μM and urolithin B-glucuronide at 15 μM activated eNOS expression. All urolithins underwent metabolic reactions, but these were limited to conjugation with sulfate moieties. This study represents a step forward in the understanding of cardiovascular health benefits of ellagitannin-rich foodstuffs and backs the idea that peripheral cells may contribute to urolithin metabolism. View Full-Text
Keywords: urolithin; ellagic acid; microbiota metabolites; endothelial cells; endothelial nitric oxide synthase; endothelial function; atherosclerosis; peripheral metabolism urolithin; ellagic acid; microbiota metabolites; endothelial cells; endothelial nitric oxide synthase; endothelial function; atherosclerosis; peripheral metabolism
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Spigoni, V.; Mena, P.; Cito, M.; Fantuzzi, F.; Bonadonna, R.C.; Brighenti, F.; Dei Cas, A.; Del Rio, D. Effects on Nitric Oxide Production of Urolithins, Gut-Derived Ellagitannin Metabolites, in Human Aortic Endothelial Cells. Molecules 2016, 21, 1009.

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