Song Jian, Kwon Oran, Chen Shenglin, Daruwala Rushad, Eck Peter, Park Jae B, Levine Mark
Molecular and Clinical Nutrition Section, Digestive Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1372, USA.
J Biol Chem. 2002 May 3;277(18):15252-60. doi: 10.1074/jbc.M110496200. Epub 2002 Feb 7.
Vitamin C and flavonoids, polyphenols with uncertain function, are abundant in fruits and vegetables. We postulated that flavonoids have a novel regulatory action of delaying or inhibiting absorption of vitamin C and glucose, which are structurally similar. From six structural classes of flavonoids, at least 12 compounds were chosen for studies. We investigated the effects of selected flavonoids on the intestinal vitamin C transporter SVCT1(h) by transfecting and overexpressing SVCT1(h) in Chinese hamster ovary cells. Flavonoids reversibly inhibited vitamin C transport in transfected cells with IC(50) values of 10-50 microm, concentrations expected to have physiologic consequences. The most potent inhibitor class was flavonols, of which quercetin is most abundant in foods. Because Chinese hamster ovary cells have endogenous vitamin C transport, we expressed SVCT1(h) in Xenopus laevis oocytes to study the mechanism of transport inhibition. Quercetin was a reversible and non-competitive inhibitor of ascorbate transport; K(i) 17.8 microm. Quercetin was a potent non-competitive inhibitor of GLUT2 expressed in Xenopus oocytes; K(i) 22.8 microm. When diabetic rats were administered glucose with quercetin, hyperglycemia was significantly decreased compared with administration of glucose alone. Quercetin also significantly decreased ascorbate absorption in normal rats given ascorbate plus quercetin compared with rats given ascorbate alone. Quercetin was a specific transport inhibitor, because it did not inhibit intestinal sugar transporters GLUT5 and SGLT1 that were injected and expressed in Xenopus oocytes. Quercetin inhibited but was not transported by SVCT1(h). Considered together, these data show that flavonoids modulate vitamin C and glucose transport by their respective intestinal transporters and suggest a new function for flavonoids.
维生素C以及功能尚不明确的黄酮类和多酚类物质在水果和蔬菜中含量丰富。我们推测，黄酮类物质对结构相似的维生素C和葡萄糖的吸收具有延缓或抑制的新调节作用。从六类结构的黄酮类物质中，选取了至少12种化合物进行研究。我们通过在中国仓鼠卵巢细胞中转染并过表达肠道维生素C转运体SVCT1(h)，研究了所选黄酮类物质对其的影响。黄酮类物质可在转染细胞中可逆性抑制维生素C转运，半数抑制浓度（IC50）值为10 - 50微摩尔，此浓度预期会产生生理效应。最有效的抑制类别是黄酮醇类，其中槲皮素在食物中最为丰富。由于中国仓鼠卵巢细胞具有内源性维生素C转运功能，我们在非洲爪蟾卵母细胞中表达SVCT1(h)以研究转运抑制机制。槲皮素是抗坏血酸转运的可逆性非竞争性抑制剂；抑制常数（Ki）为17.8微摩尔。槲皮素是非洲爪蟾卵母细胞中表达的葡萄糖转运蛋白2（GLUT2） 的有效非竞争性抑制剂；抑制常数（Ki）为22.8微摩尔。给糖尿病大鼠喂食含槲皮素的葡萄糖时, 与单独喂食葡萄糖相比，高血糖症显著降低。与单独给予抗坏血酸的大鼠相比，给予抗坏血酸加槲皮素的正常大鼠中，槲皮素也显著降低了抗坏血酸的吸收。槲皮素是一种特异性转运抑制剂，因为它不抑制注射并在非洲爪蟾卵母细胞中表达的肠道糖转运蛋白GLUT5和钠葡萄糖协同转运蛋白1（SGLT1）。槲皮素抑制SVCT1(h)但不被其转运。综合来看，这些数据表明黄酮类物质通过各自的肠道转运体调节维生素C和葡萄糖的转运，并提示了黄酮类物质的一种新功能。
