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 PGE₂, 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

Consumption of macronutrients, fiber, ethanol and main food groups.

<p>Consumption of macronutrients, fiber, ethanol and main food groups.</p

Fat and muscle body composition parameters.

<p>Fat and muscle body composition parameters.</p

Changes induced in relative abundance of gut bacteria species by lifestyle in women.

<p>(A) <i>Bifidobacterium longum</i>, <i>(</i>B) <i>Faecalibacterium prausnitzii</i>, (C) <i>Roseburia hominis</i>, (D) <i>Akkermansia muciniphila</i>. Data were log transformed and analyzed by t-test * p<0.05 **p<0.01.</p

Bacterial phyla and families in feces of active and sedentary women.

<p>Bacterial phyla and families in feces of active and sedentary women.</p

Spearman correlation of microbiota genera, body composition and physical activity parameters.

<p>Spearman correlation of microbiota genera, body composition and physical activity parameters.</p

Multivariate linear regression analysis of the bacterial groups significantly different between active and sedentary women as dependent variants, and diet composition, fecal water, body composition parameters and physical activity parameters as independent variables.

<p>Multivariate linear regression analysis of the bacterial groups significantly different between active and sedentary women as dependent variants, and diet composition, fecal water, body composition parameters and physical activity parameters as independent variables.</p

A Dietary Resveratrol-Rich Grape Extract Prevents the Developing of Atherosclerotic Lesions in the Aorta of Pigs Fed an Atherogenic Diet

The presence of grape and wine polyphenol resveratrol (RES) in the diet is negligible. Therefore, the cardiovascular benefits of this molecule, in a dietary context, remain to be established. We aimed to investigate, through dietary intervention, the effects of a resveratrol-rich grape extract (GE-RES) on the prevention of early aortic lesions in pigs fed an atherogenic diet (AD). These effects were compared with those produced by a grape extract lacking RES (GE) or RES alone. Pigs fed the AD for 4 months showed early atherosclerotic lesions in the thoracic aorta: degeneration and fragmentation of elastic fibers, increase of intima thickness, subendothelial fibrosis, and accumulation of fatty cells and anion superoxide radicals. GE-RES was the most effective treatment and prevented the disruption of aortic elastic fibers, decreased their alteration (57%), and reduced the intima thickness (33%) and the accumulation of fatty cells (42%) and O₂^•– (38%) in aortic tissue. In addition, GE-RES moderately downregulated the expression of the suppressors of cytokine signaling 1 (<i>SOCS1</i>) and 3 (<i>SOCS3</i>), key regulators of vascular cell responses, in peripheral mononuclear blood cells. Our results suggest that the consumption of this GE-RES nutraceutical, in a dietary prevention context, could prevent early atherosclerotic events. The presence of RES in the grape extract strengthened these effects

Effects of the consumption of RE on body weight (g) and food utility index (FUI) in Zucker female rats.

<p>Lean (Le) and obese (Ob) rats were fed the control diet (CT) or the diet supplemented with 0.05% of RE (RE) for 64 days. Data are presented as the mean value ± SD (n = 7 for lean animals and n = 5 for obese animals). * <i>P</i><0.05, ** <i>P</i><0.01 compared to their respective CT values.</p

Effect of the RE-supplementation on gut enzyme activity.

<p>α-Amylase activity in the small intestine and β-glucosidase activity in the caecum of obese (Ob) and lean (Le) Zucker female rats. Results are shown as % of inhibition respect to the activity in the corresponding control (CT) group.</p