Influence of gut flora-derived ellagitannins' metabolites- urolithins on production and release of pro-inflammatory factors from stimulated neutrophils in the context of cardiovascular disease prevention

Abstract

Ellagitannin-rich products were proven to have beneficial influence on cardiovascular system [1 – 2]. Due to not well-established bioavailability of ellagitannins nowadays their gut flora derived metabolites- urolithins become a target in research of factors responsible for clinical effects. Because of the important role of neutrophils in the development of pathologies in cardiovascular system [3], the influence of urolithins A, B and C on their pro-inflammatory functions was tested. Urolithin B at concentration of 20µM showed significant inhibition of IL-1β, IL-8 and MMP-9 production induced by LPS (26.5 ± 6.2, 31.6 ± 1.7, 49.6 ± 7.7% respectively). Urolithin C was the only active compound towards inhibition of elastase release from cytochalasin A/f-MLP stimulated neutrophils. At concentration 5 and 20µM urolithin C decreased the elastase level by 39.0 ± 6.1 and 66.6 ± 2.9% respectively. Myeloperoxidase release was strongly inhibited by urolithin A and C (at 20µM by 46.7 ± 4.6 and 63.8 ± 3.1% respectively). Urolithin A was the strongest ROS release inhibitor both in f-MLP and PMA stimulated neutrophils. At the concentration of 1µM caused ROS level decrease by 42.6 ± 8.9 and 53.7 ± 5.4% respectively. Obtained results indicate, that urolithins can specifically modulate inflammatory functions of neutrophils, and thus at least partially explain observed beneficial effects of ellagitannin-rich food products, nutraceuticals and medicinal plants on cardiovascular system.