Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo, Japan.
J Pharm Pharm Sci. 2012;15(2):256-64. doi: 10.18433/j38k56.
Lutein is a carotenoid mainly found in green leafy vegetables and is located in the macula lutea in the human eye. Since humans cannot synthesize lutein de novo, it must be digested as food. The physiological importance of an orally administered compound depends on its interaction with target tissues. It is therefore important to clarify the absorption mechanism in the intestine. Cholesterol membrane transporters Niemann-Pick C1 Like 1 (NPC1L1) and scavenger receptor class B type 1 (SR-B1) are involved in the intestinal absorption of highly lipophilic compounds including cholesterol. Ezetimibe, a selective inhibitor of intestinal NPC1L1, is the widespread lipid-lowering agent. It is important to investigate the possibility of food-drug interactions in order to prevent undesirable and harmful clinical consequences. The aim of this work was to determine whether NPC1L1, SR-B1 and other transporters are involved in absorption of lutein.
Caco-2 cells were used for accumulation and permeability study of lutein. Lutein concentration was determined by an HPLC system. The cDNA of transporters was isolated from total RNA of Caco-2 cells, and the expression of these transporters was confirmed by RT-PCR (reverse transcription-polymerase chain reaction).
Ezetimibe inhibited up to 40% of lutein accumulation by Caco-2 cell monolayers. Block lipid transport 1 (BLT-1), a selective chemical inhibitor of SR-B1, also inhibited lutein accumulation by Caco-2 cells. On the other hand, ATP-depletion reagents (sodium fluoride and sodium azide or carbonyl cyanide m-chlorophenylhydrazone) did not influence the accumulation or permeation of lutein significantly.
The results show that lutein absorption is, at least in part, mediated by influx transporters NPC1L1 and SR-B1 rather than mediated by efflux transporters such as ABC (ATP-binding cassette) transporters.
叶黄素是一种主要存在于绿叶蔬菜中的类胡萝卜素，位于人眼的黄斑区。由于人体不能从头合成叶黄素，因此必须作为食物进行消化。口服化合物的生理重要性取决于其与靶组织的相互作用。因此，阐明肠道中的吸收机制很重要。胆固醇膜转运蛋白 Niemann-Pick C1 样 1（NPC1L1）和清道夫受体 B 类 1 型（SR-B1）参与包括胆固醇在内的高度亲脂性化合物的肠道吸收。依泽替米贝是一种选择性的肠道 NPC1L1 抑制剂，是广泛使用的降脂药物。为了防止不良和有害的临床后果，有必要研究食物-药物相互作用的可能性。本研究旨在确定 NPC1L1、SR-B1 和其他转运蛋白是否参与叶黄素的吸收。
Caco-2 细胞用于叶黄素的积累和渗透性研究。通过 HPLC 系统测定叶黄素浓度。从 Caco-2 细胞总 RNA 中分离转运蛋白的 cDNA，并通过 RT-PCR（逆转录-聚合酶链反应）确认这些转运蛋白的表达。
依泽替米贝抑制 Caco-2 细胞单层中高达 40%的叶黄素积累。BLT-1（选择性 SR-B1 化学抑制剂）也抑制 Caco-2 细胞中叶黄素的积累。另一方面，ATP 耗竭试剂（氟化钠和叠氮化钠或羰基氰化物 m-氯苯腙）对叶黄素的积累或渗透没有显著影响。
结果表明，叶黄素的吸收至少部分是由内流转运蛋白 NPC1L1 和 SR-B1 介导的，而不是由 ABC（ATP 结合盒）转运蛋白等外排转运蛋白介导的。
