1 research outputs found
Intestinal Ellagitannin Metabolites Ameliorate Cytokine-Induced Inflammation and Associated Molecular Markers in Human Colon Fibroblasts
Pomegranate ellagitannins
(ETs) are transformed in the gut to ellagic
acid (EA) and its microbiota metabolites, urolithin A (Uro-A) and
urolithin B (Uro-B). These compounds exert anti-inflammatory effects
in vitro and in vivo. The aim of this study was to investigate the
effects of Uro-A, Uro-B, and EA on colon fibroblasts, cells that play
a key role in intestinal inflammation. CCD18-Co colon fibroblasts
were exposed to a mixture of Uro-A, Uro-B, and EA, at concentrations
comparable to those found in the colon (40 μM Uro-A, 5 μM
Uro-B, 1 μM EA), both in the presence or in the absence of IL-1β
(1 ng/mL) or TNF-α (50 ng/mL), and the effects on fibroblast
migration and monocyte adhesion were determined. The levels of several
growth factors and adhesion cytokines were also measured. The mixture
of metabolites significantly inhibited colon fibroblast migration
(∼70%) and monocyte adhesion to fibroblasts (∼50%).
These effects were concomitant with a significant down-regulation
of the levels of PGE<sub>2</sub>, PAI-1, and IL-8, as well as other
key regulators of cell migration and adhesion. Of the three metabolites
tested, Uro-A exhibited the most significant anti-inflammatory effects.
The results show that a combination of the ET metabolites found in
colon, urolithins and EA, at concentrations achievable in the intestine
after the consumption of pomegranate, was able to moderately improve
the inflammatory response of colon fibroblasts and suggest that consumption
of ET-containing foods has potential beneficial effects on gut inflammatory
diseases