title: Antiatherogenic effects of ellagic acid and urolithins in vitro.
abstract: Atherosclerosis, one of the leading causes of death worldwide, is characterized by impaired endothelial function and lipid metabolism, among other factors. Ellagitannins are a class of phenolic compounds that may play a role in cardiovascular health. This work aimed to study the potential atheroprotective effects of urolithins, ellagitannin-derived gut microbiota metabolites, on different key factors in atherosclerosis development: the ability of monocytes to adhere to endothelial cells and the uptake and efflux of cholesterol by macrophages. The biotransformations urolithins undergo in peripheral cells were also evaluated. Results indicated that some urolithins and ellagic acid were able to reduce the adhesion of THP-1 monocytes to human umbilical vein endothelial cells (HUVECs) and the secretion of a cellular adhesion molecule (sVCAM-1) and pro-inflammatory cytokine (IL-6). Urolithin C, a combination of urolithins A and B, and ellagic acid also decreased the accumulation of cholesterol in THP-1-derived macrophages, but they were not able to promote cholesterol efflux. The analysis of cell media by UHPLC-ESI-MS(n) indicated urolithins and ellagic underwent extensive metabolism, with sulfate and methyl conjugation. This evidence indicates that atherosclerotic processes may be attenuated by urolithins, but future human intervention trials are required to establish if is translated in vivo.
authors.affiliation: Human Nutrition Unit, Department of Food Science, University of Parma, Via Volturno 39, 43125 Parma, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Mele
authors.affiliation: Human Nutrition Unit, Department of Food Science, University of Parma, Via Volturno 39, 43125 Parma, Italy.
authors.forename: Pedro
authors.initials: P
authors.lastname: Mena
authors.affiliation: Department of Pharmacy, University of Parma, Viale delle Scienze 27a, 43124 Parma, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Piemontese
authors.affiliation: Department of Pharmacy, University of Parma, Viale delle Scienze 27a, 43124 Parma, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Marino
authors.affiliation: Group "Analytical Chemistry of Contaminants", Department of Chemistry and Physics (Analytical Chemistry Area), University of Almería, Carretera de Sacramento s/n, E-04120 Almería, Spain.
authors.forename: Noelia
authors.initials: N
authors.lastname: López-Gutiérrez
authors.affiliation: Department of Pharmacy, University of Parma, Viale delle Scienze 27a, 43124 Parma, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Bernini
authors.affiliation: Human Nutrition Unit, Department of Food Science, University of Parma, Via Volturno 39, 43125 Parma, Italy.
authors.forename: Furio
authors.initials: F
authors.lastname: Brighenti
authors.affiliation: Department of Pharmacy, University of Parma, Viale delle Scienze 27a, 43124 Parma, Italy. Electronic address: ilaria.zanotti@unipr.it.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Zanotti
authors.affiliation: Human Nutrition Unit, Department of Food Science, University of Parma, Via Volturno 39, 43125 Parma, Italy; The Need for Nutrition Education/Innovation Programme (NNEdPro), University of Cambridge, Cambridge, UK. Electronic address: daniele.delrio@unipr.it.
authors.forename: Daniele
authors.initials: D
authors.lastname: Del Rio
mesh_terms: D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism*; D003374:Coumarins / Q000494:pharmacology*; D004610:Ellagic Acid / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D003374:Coumarins; D047348:Hydrolyzable Tannins; C508600:IL6 protein, human; D015850:Interleukin-6; D019010:Vascular Cell Adhesion Molecule-1; C000595064:urolithin B; C588364:urolithin C; C026423:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one; D004610:Ellagic Acid; D002784:Cholesterol
keywords: Atherosclerosis; Cholesterol transport; Ellagitannin metabolites; Endothelial function; Peripheral metabolism; Urolithins