Dietary supplementation with ipriflavone decreases hepatic iron stores in wild type mice
Dietary supplementation with ipriflavone decreases hepatic iron stores in wild type mice
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DOI：
10.1016/j.bcmd.2016.05.004
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发表时间：
2016-09-01
影响因子：
2.3
通讯作者：
Fraenkel, Paula G.
中科院分区：
文献类型：
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作者：
Patchen, Bonnie;Koppe, Tiago;Fraenkel, Paula G.
铁调素，一种在肝脏中产生的肽，通过引起铁输出蛋白ferroportin的降解来减少肠铁吸收和巨噬细胞铁释放。由于铁调素在铁超载综合征患者中的水平不适当地低，因此铁调素是一个潜在的药物靶点。我们先前进行了一项化学筛选，揭示了依普黄酮，一种口服小分子，作为铁调素表达的有效诱导剂。为了评估依普黄酮对铁稳态的影响，我们将5周龄野生型或中间型地中海贫血（Hbb（Th 3 +/-））小鼠组置于无大豆、铁充足的饮食中，AIN-93 G含有220 mg铁和0-750 mg依普黄酮/kg食物，持续50天。依普黄酮500 mg/kg显著降低WT小鼠的肝脏铁储备和肠铁转运蛋白表达，同时增加铁调素转录水平与肝脏铁储备的比率。在Hbb（Th 3 +/-）小鼠中补充依普黄酮未能缓解铁过载，并且与肠铁转运蛋白的轻度减少以及未能改变铁调素转录水平与肝脏铁储存或铁调素调节激素erythroferrone的脾脏表达的比率相关。这些数据表明，饮食中单独补充依普黄酮不足以治疗中间型地中海贫血的铁超载。(C)2016 Elsevier Inc. All rights reserved.
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 220 mg iron and 0-750 mg ipriflavone/kg of food for 50 days. Ipriflavone 500 mg/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. (C) 2016 Elsevier Inc. All rights reserved.