Tun Temdara, Kang Young-Sook
College of Pharmacy, Drug Information Research Institute and Research Center for Cell Fate Control, Sookmyung Women's University, Seoul 04310, Republic of Korea.
Biomol Ther (Seoul). 2017 Jul 1;25(4):441-451. doi: 10.4062/biomolther.2017.082.
Imperatorin, a major bioactive furanocoumarin with multifunctions, can be used for treating neurodegenerative diseases. In this study, we investigated the characteristics of imperatorin transport in the brain. Experiments of the present study were designed to study imperatorin transport across the blood-brain barrier both and . study was performed in rats using single intravenous injection and in situ carotid artery perfusion technique. Conditionally immortalized rat brain capillary endothelial cells were as an model of blood-brain barrier to examine the transport mechanism of imperatorin. Brain distribution volume of imperatorin was about 6 fold greater than that of sucrose, suggesting that the transport of imperatorin was through the blood-brain barrier in physiological state. Both and imperatorin transport studies demonstrated that imperatorin could be transported in a concentration-dependent manner with high affinity. Imperatorin uptake was dependent on proton gradient in an opposite direction. It was significantly reduced by pretreatment with sodium azide. However, its uptake was not inhibited by replacing extracellular sodium with potassium or -methylglucamine. The uptake of imperatorin was inhibited by various cationic compounds, but not inhibited by TEA, choline and organic anion substances. Transfection of plasma membrane monoamine transporter, organic cation transporter 2 and organic cation/carnitine transporter 2/1 siRNA failed to alter imperatorin transport in brain capillary endothelial cells. Especially, tramadol, clonidine and pyrilamine inhibited the uptake of [H]imperatorin competitively. Therefore, imperatorin is actively transported from blood to brain across the blood-brain barrier by passive and carrier-mediated transporter.
欧前胡素是一种具有多种功能的主要生物活性呋喃香豆素，可用于治疗神经退行性疾病。在本研究中，我们研究了欧前胡素在脑内的转运特性。本研究的实验旨在研究欧前胡素穿过血脑屏障的情况，采用单次静脉注射和原位颈动脉灌注技术在大鼠身上进行研究。将条件永生化大鼠脑微血管内皮细胞作为血脑屏障的模型来研究欧前胡素的转运机制。欧前胡素的脑分布体积比蔗糖大6倍左右，表明欧前胡素在生理状态下可通过血脑屏障转运。欧前胡素的转运研究均表明，欧前胡素能够以高亲和力呈浓度依赖性转运。欧前胡素的摄取依赖于相反方向的质子梯度。用叠氮化钠预处理可使其显著降低。然而，用钾或甲基葡糖胺替代细胞外钠并不会抑制其摄取。欧前胡素的摄取受到各种阳离子化合物的抑制，但不受TEA、胆碱和有机阴离子物质的抑制。转染质膜单胺转运体、有机阳离子转运体2和有机阳离子/肉碱转运体2/1的小干扰RNA未能改变脑微血管内皮细胞中欧前胡素的转运。特别是，曲马多、可乐定和吡苄明竞争性抑制[H]欧前胡素的摄取。因此，欧前胡素通过被动和载体介导的转运体从血液主动转运至脑内，穿过血脑屏障。
