Laboratoire d'Innovation Thérapeutique, Université Louis Pasteur, Faculté de Pharmacie, Strasbourg, France.
J Pharm Pharmacol. 2009 Nov;61(11):1473-83. doi: 10.1211/jpp/61.11.0006.
Flavonoids are phenolic compounds found in most edible fruits and vegetables. Previous studies have demonstrated their biological and beneficial effects on human health. However, their bioavailability and, in particular, their intestinal absorption mechanism have not yet been clearly identified. The aim of our work was to quantify and to characterize in vitro the nature of the transport of two flavonoids distinguished by their physicochemical and pharmacological properties: quercetin, a flavan-3-ol, and naringenin, a flavanone.
Differentiated and polarized Caco-2 human intestinal epithelial cell lines were used for this purpose.
In our experimental conditions, quercetin and naringenin were poorly absorbed by Caco-2 cells. Quercetin was absorbed by passive diffusion and a pH-dependent mechanism mediated by the organic anion transporting protein B (OATP-B). It was not a multidrug resistance associated protein (MRP)1 substrate, but was substrate of the MRP2 efflux transporter and not P-glycoprotein (P-gp). Intestinal permeability from the apical to the basolateral side was higher for naringenin than for quercetin, which was partly explained by naringenin's physicochemical characteristics. Naringenin, partially absorbed by passive diffusion, was also an ATP-dependent transport substrate mediated by MRP1, but was not an OATP-B substrate. However, naringenin was secreted via active P-gp and MRP2 efflux transporters.
The contribution of ATP-dependent efflux transporters (MRP2 and P-gp) to the permeability of these compounds in the apical side could explain their low bioavailability. In conclusion, knowledge of the absorption mechanism of these two flavonoids was used to determine the intake level that has a beneficial effect on human health and their putative role in food-drug interactions.
类黄酮是存在于大多数可食用水果和蔬菜中的酚类化合物。先前的研究表明，它们对人类健康具有生物和有益的影响。然而，它们的生物利用度，特别是其肠道吸收机制尚未明确确定。我们的工作旨在定量和表征两种类黄酮的体外运输性质，这两种类黄酮因其理化和药理学特性而有所区别：槲皮素，一种黄烷-3-醇，和柚皮素，一种黄烷酮。
为此目的使用了分化和极化的 Caco-2 人肠道上皮细胞系。
在我们的实验条件下，槲皮素和柚皮素被 Caco-2 细胞吸收不良。槲皮素通过被动扩散和由有机阴离子转运蛋白 B（OATP-B）介导的 pH 依赖性机制被吸收。它不是多药耐药相关蛋白 1（MRP1）的底物，但却是 MRP2 外排转运蛋白的底物，而不是 P-糖蛋白（P-gp）。柚皮从顶侧向基底侧的通透性高于槲皮素，这部分解释了柚皮素的物理化学特性。部分通过被动扩散吸收的柚皮素也是由 MRP1 介导的 ATP 依赖性转运底物，但不是 OATP-B 底物。然而，柚皮素通过主动 P-gp 和 MRP2 外排转运蛋白被分泌。
ATP 依赖性外排转运蛋白（MRP2 和 P-gp）对这些化合物在顶侧的渗透性的贡献可以解释它们的低生物利用度。总之，对这两种类黄酮吸收机制的了解用于确定对人体健康有益的摄入水平及其在食物-药物相互作用中的潜在作用。
