title: Dietary supplementation with ipriflavone decreases hepatic iron stores in wild type mice.
abstract: Hepcidin, a peptide produced in the liver, decreases intestinal iron absorption and macrophage iron release by causing degradation of the iron exporter, ferroportin. Because its levels are inappropriately low in patients with iron overload syndromes, hepcidin is a potential drug target. We previously conducted a chemical screen that revealed ipriflavone, an orally available small molecule, as a potent inducer of hepcidin expression. To evaluate ipriflavone's effect on iron homeostasis, we placed groups of 5-week old wild type or thalassemia intermedia (Hbb(Th3+/-)) mice on a soy-free, iron-sufficient diet, AIN-93G containing 220mg iron and 0-750mgipriflavone/kg of food for 50days. Ipriflavone 500mg/kg significantly reduced liver iron stores and intestinal ferroportin expression in WT mice, while increasing the ratio of hepcidin transcript levels to liver iron stores. Ipriflavone supplementation in Hbb(Th3+/-) mice failed to alleviate iron overload and was associated with a milder reduction in intestinal ferroportin and a failure to alter the ratio of hepcidin transcript levels to liver iron stores or splenic expression of the hepcidin-regulatory hormone, erythroferrone. These data suggest that dietary supplementation with ipriflavone alone would not be sufficient to treat iron overload in thalassemia intermedia.
authors: Division of Hematology/Oncology, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, MA.
authors: Bonnie
authors: B
authors: Patchen
authors: Division of Hematology/Oncology, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, MA.
authors: Tiago
authors: T
authors: Koppe
authors: Division of Hematology/Oncology, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, MA.
authors: Aaron
authors: A
authors: Cheng
authors: Departments of Genetics and Complex Diseases and Nutrition, Harvard School of Public Health, Boston, MA.
authors: Young Ah
authors: YA
authors: Seo
authors: Departments of Genetics and Complex Diseases and Nutrition, Harvard School of Public Health, Boston, MA.
authors: Marianne
authors: M
authors: Wessling-Resnick
authors: Division of Hematology/Oncology, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, MA.
authors: Paula G
authors: PG
authors: Fraenkel
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000187:drug effects; D019587:Dietary Supplements; D064451:Hepcidins / Q000235:genetics; D007501:Iron / Q000008:administration & dosage / Q000378:metabolism*; D019190:Iron Overload / Q000188:drug therapy* / Q000517:prevention & control; D007529:Isoflavones / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000187:drug effects; D017211:Treatment Failure; D017086:beta-Thalassemia / Q000188:drug therapy; D000098742:Ferroportin
chemical_list: D027682:Cation Transport Proteins; D064451:Hepcidins; D007529:Isoflavones; D012333:RNA, Messenger; D000098742:Ferroportin; C018986:ipriflavone; D007501:Iron
keywords: Ferroportin; Hemoglobinopathy; Hepcidin; Iron; Thalassemia