Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima, Japan.
J Pharm Pharmacol. 2013 Jul;65(7):1037-43. doi: 10.1111/jphp.12062. Epub 2013 Apr 3.
The aim of this study was to investigate the transporter-mediated transport of N-acetyl 5-aminosalicylic acid (Ac-5-ASA) and the effect of quercetin on Ac-5-ASA transport.
Caco-2 cell monolayers grown in Transwells were used to study the transport of Ac-5-ASA in the absence or presence of quercetin, and apical-to-basolateral and basolateral-to-apical apparent permeability (PappAB and PappBA values, respectively) was determined. The effect of transporter inhibitors, such as MK571, quinidine and mitoxantrone, on the transport of Ac-5-ASA was investigated.
In the absence of transporter mediators, the transport of Ac-5-ASA was much higher in the basolateral-to-apical direction than in the opposite direction. The PappBA/PappAB ratio of Ac-5-ASA was 4.89. Quercetin inhibited the apical efflux of Ac-5-ASA and decreased the PappBA/PappAB ratio to 1.05. Of the transporter inhibitors, MK571 decreased the PappBA/PappAB ratio to 1.07; however, neither quinidine nor mitoxantrone had an effect on Ac-5-ASA transport.
Ac-5-ASA was excreted by multidrug resistance-associated protein 2 from Caco-2 cells, and its transport was inhibited by quercetin. Our findings suggest that dose levels of sulfasalazine or 5-aminosalicylic acid can be decreased by coadministration of quercetin, leading to improved pharmaceutical care for inflammatory bowel diseases.
本研究旨在探讨 N-乙酰-5-氨基水杨酸（Ac-5-ASA）的转运体介导转运及其与槲皮素相互作用对 Ac-5-ASA 转运的影响。
采用 Transwell 中培养的 Caco-2 细胞单层模型，研究 Ac-5-ASA 在无槲皮素或槲皮素存在时的转运情况，并测定其顶侧至基底侧（PappAB）和基底侧至顶侧（PappBA）表观渗透系数。同时考察了 MK571、奎尼丁和米托蒽醌等转运体抑制剂对 Ac-5-ASA 转运的影响。
在无转运体介导物的情况下，Ac-5-ASA 从基底侧向顶侧的转运明显高于相反方向。Ac-5-ASA 的 PappBA/PappAB 比值为 4.89。槲皮素抑制 Ac-5-ASA 的顶端外排，使 PappBA/PappAB 比值降低至 1.05。MK571 降低 PappBA/PappAB 比值至 1.07；然而，奎尼丁和米托蒽醌对 Ac-5-ASA 转运均无影响。
Ac-5-ASA 由 Caco-2 细胞中的多药耐药相关蛋白 2 排出，其转运被槲皮素抑制。本研究结果表明，与磺胺吡啶或 5-氨基水杨酸合用可降低剂量水平的槲皮素，从而改善炎症性肠病的药物治疗。
