Molecular Nutrition Research, Interdisciplinary Research Center, Justus-Liebig-University of Giessen, Giessen, Germany.
Mol Nutr Food Res. 2012 Nov;56(11):1627-35. doi: 10.1002/mnfr.201200370. Epub 2012 Sep 11.
Based on the studies suggesting that active transport mechanisms contribute to the absorption of flavonoids into human intestinal Caco-2 cells, we here used the structurally similar fluorescent rhodamine 123 to test a possible influence of flavonoids on its uptake.
Rhodamine absorption displayed saturation kinetics with a K(m) of 1.1 μM and a pH-optimum of 8.5 and was stimulated by flavone four-fold in its V(max) . Ring C of the other 16 flavonoids tested turned out to be of special importance in order to act as potent inhibitors for rhodamine transport, with a positive charge there, as present in the anthocyanidins, or a 2,3 double bond together with an aromatic ring fused to position 2, as present in flavones and flavonols, being essential structural requirements. Flavone-stimulated rhodamine uptake was unaffected by classical substrates of organic cation transporters or inhibitors of adenosine triphosphate (ATP)-dependent efflux pumps. Also, inhibitors of mitogen-activated protein kinases or tyrosine kinases did not influence the transport, whose stimulation, however, was essentially dependent on the simultaneous presence of flavone. The existence of a flavone-activated apical flavonoid transporter in Caco-2 cells was finally associated with the potently diminished transepithelial apical to basolateral fluxes of (14) C-kaempferol in the presence of competing unlabeled flavonoid substrates.
In conclusion, flavone activates an as yet unidentified transporter for flavonoids in the apical membrane of Caco-2 cells.
基于研究表明主动转运机制有助于黄酮类化合物被人体肠道 Caco-2 细胞吸收，我们使用结构相似的荧光罗丹明 123 来检测黄酮类化合物对其摄取的可能影响。
罗丹明吸收显示出米氏常数（K(m)）为 1.1 μM 和 pH 最佳值为 8.5 的饱和动力学，黄酮类化合物将其 V(max)增加了四倍。在所测试的其他 16 种黄酮类化合物中，C 环对于作为有效的罗丹明转运抑制剂特别重要，其中存在正电荷，如在花色苷中，或者存在 2,3 双键以及与位置 2 融合的芳环，如在黄酮类和黄酮醇中，是必需的结构要求。黄酮类化合物刺激的罗丹明摄取不受有机阳离子转运体的经典底物或三磷酸腺苷（ATP）依赖性外排泵抑制剂的影响。此外，丝裂原活化蛋白激酶或酪氨酸激酶抑制剂也不会影响运输，但其刺激基本上取决于黄酮类化合物的同时存在。在 Caco-2 细胞中，存在一种黄酮类激活的顶端黄酮类转运体，这与在竞争未标记的黄酮类化合物底物存在的情况下，（14）C-山奈酚的跨上皮顶端到基底外侧通量显著减少有关。
总之，黄酮类化合物激活了 Caco-2 细胞顶膜中一种尚未确定的黄酮类转运体。
