title: Quercetin inhibits intestinal iron absorption and ferroportin transporter expression in vivo and in vitro.
abstract: Balancing systemic iron levels within narrow limits is critical for maintaining human health. There are no known pathways to eliminate excess iron from the body and therefore iron homeostasis is maintained by modifying dietary absorption so that it matches daily obligatory losses. Several dietary factors can modify iron absorption. Polyphenols are plentiful in human diet and many compounds, including quercetin--the most abundant dietary polyphenol--are potent iron chelators. The aim of this study was to investigate the acute and longer-term effects of quercetin on intestinal iron metabolism. Acute exposure of rat duodenal mucosa to quercetin increased apical iron uptake but decreased subsequent basolateral iron efflux into the circulation. Quercetin binds iron between its 3-hydroxyl and 4-carbonyl groups and methylation of the 3-hydroxyl group negated both the increase in apical uptake and the inhibition of basolateral iron release, suggesting that the acute effects of quercetin on iron transport were due to iron chelation. In longer-term studies, rats were administered quercetin by a single gavage and iron transporter expression measured 18 h later. Duodenal FPN expression was decreased in quercetin-treated rats. This effect was recapitulated in Caco-2 cells exposed to quercetin for 18 h. Reporter assays in Caco-2 cells indicated that repression of FPN by quercetin was not a transcriptional event but might be mediated by miRNA interaction with the FPN 3'UTR. Our study highlights a novel mechanism for the regulation of iron bioavailability by dietary polyphenols. Potentially, diets rich in polyphenols might be beneficial for patients groups at risk of iron loading by limiting the rate of intestinal iron absorption.
authors: Research Department of Structural and Molecular Biology, Division of Biosciences, University College London, London, United Kingdom; Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences University of Novi Sad, Novi Sad, Serbia.
authors: Marija
authors: M
authors: Lesjak
authors: Diabetes & Nutritional Sciences Division, King's College London, London, United Kingdom.
authors: Rukshana
authors: R
authors: Hoque
authors: Research Department of Structural and Molecular Biology, Division of Biosciences, University College London, London, United Kingdom.
authors: Sara
authors: S
authors: Balesaria
authors: Research Department of Structural and Molecular Biology, Division of Biosciences, University College London, London, United Kingdom.
authors: Vernon
authors: V
authors: Skinner
authors: Research Department of Neuroscience, Physiology and Pharmacology, Division of Biosciences, University College London, Royal Free Campus, London, United Kingdom.
authors: Edward S
authors: ES
authors: Debnam
authors: Research Department of Structural and Molecular Biology, Division of Biosciences, University College London, London, United Kingdom.
authors: Surjit K S
authors: SK
authors: Srai
authors: Diabetes & Nutritional Sciences Division, King's College London, London, United Kingdom.
authors: Paul A
authors: PA
authors: Sharp
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D018938:Caco-2 Cells; D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D007502:Iron Chelating Agents / Q000494:pharmacology*; D019266:Iron, Dietary / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000098742:Ferroportin
chemical_list: D020413:3' Untranslated Regions; D027682:Cation Transport Proteins; D007502:Iron Chelating Agents; D019266:Iron, Dietary; D035683:MicroRNAs; D000098742:Ferroportin; D011794:Quercetin