title: Intestinal ellagitannin metabolites ameliorate cytokine-induced inflammation and associated molecular markers in human colon fibroblasts.
abstract: 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(2), 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.
authors.affiliation: Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology,  CEBAS-CSIC , P.O. Box 164, 30100 Campus de Espinardo, Murcia, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Giménez-Bastida
authors.forename: Mar
authors.initials: M
authors.lastname: Larrosa
authors.forename: Antonio
authors.initials: A
authors.lastname: González-Sarrías
authors.forename: Francisco
authors.initials: F
authors.lastname: Tomás-Barberán
authors.forename: Juan C
authors.initials: JC
authors.lastname: Espín
authors.forename: María-Teresa
authors.initials: MT
authors.lastname: García-Conesa
mesh_terms: D000893:Anti-Inflammatory Agents / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001711:Biotransformation; D002460:Cell Line; D002465:Cell Movement; D003106:Colon / Q000276:immunology*; D003374:Coumarins / Q000276:immunology* / Q000378:metabolism; D004610:Ellagic Acid / Q000276:immunology* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology*; D006801:Humans; D047348:Hydrolyzable Tannins / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology; D029561:Lythraceae / Q000737:chemistry; D010936:Plant Extracts / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D003374:Coumarins; D047348:Hydrolyzable Tannins; D053583:Interleukin-1beta; D016209:Interleukin-8; D010936:Plant Extracts; D017395:Plasminogen Activator Inhibitor 1; D014409:Tumor Necrosis Factor-alpha; C026423:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one; D004610:Ellagic Acid