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.
Highlights
The endothelium is a key regulator of vascular homeostasis, representing a selective barrier, and modulating circulating blood cell adhesion, smooth muscle cell proliferation, and inflammation
To establish whether urolithins could modulate vascular reactivity in a non-inflammatory scenario, the production of nitric oxide (NO) was studied in non-stimulated conditions
Since NO is a gaseous molecule with a short half-life, nitrite (NO2 ́ ) and nitrate (NO3 ́ ) levels—which represent the stable degradation products of NO accumulating in supernatants of cell culture—were assessed at 5 min and at 24 h as an integrated measure of NO production [31,32,33]
Summary
The endothelium is a key regulator of vascular homeostasis, representing a selective barrier, and modulating circulating blood cell adhesion, smooth muscle cell proliferation, and inflammation. It plays a crucial role in the maintenance of vascular tone by regulating the fine-tuned balance between vasodilation and vasoconstriction [1]. Is the most important endothelium-dependent vasodilator produced by the endothelial nitric oxide synthase (eNOS) in blood vessels. Endothelial dysfunction is a reversible process and effective strategies in maintaining or improving vascular homeostasis are of critical interest for cardiovascular disease (CVD) prevention. Phenolic compounds may exert protective actions against atherosclerosis and other CVDs [3,4,5,6]
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