Influence of Gut Microbiota-Derived Ellagitannins' Metabolites Urolithins on Pro-Inflammatory Activities of Human Neutrophils

Ellagitannin-rich products exhibit beneficial influence in the case of inflammation-associated diseases. Urolithins, metabolites of ellagitannins produced by gut microbiota, in contrary to high molecular weight hydrophilic parental polyphenols, possess well established bioavailability. Because of the important role of neutrophils in progression of inflammation, the influence of urolithins on their pro-inflammatory functions was tested. Urolithin B at a concentration of 20 mu M showed significant inhibition of interleukin 8 and extracellular matrix-degrading enzyme MMP-9 production. It was also significantly active in prevention of cytochalasin A/formyl-met-leuphenylalanine-triggered selectin CD62L shedding. Urolithin C was the only active compound towards inhibition of elastase release from cyto-chalasin A/formyl-met-leu-phenylalanine-stimulated neutrophils with 39.0 +/- 15.9% inhibition at a concentration of 5 mu M. Myeloperoxidase release was inhibited by urolithins A and C (at 20 mu M by 46.7 +/- 16.1 and 63.8 +/- 8.6%, respectively). Urolithin A was the most potent reactive oxygen species release inhibitor both in formyl-met-leu-phenylalanine and 4 beta-phorbol-12 beta-myristate-R13-acetate-stimulated neutrophils. At the concentration of 1 mu M, it caused reactive oxygen species level decrease by 42.6 +/- 26.6 and 53.7 +/- 16.0%, respectively. Urolithins can specifically modulate inflammatory functions of neutrophils, and thus could contribute to the beneficial health effects of ellagitannin-rich medicinal plant materials and food products.