Prediction of intestinal absorption and metabolism of pharmacologically active flavones and flavanones
Prediction of intestinal absorption and metabolism of pharmacologically active flavones and flavanones
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DOI：
10.1016/j.bmc.2008.01.028
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发表时间：
2008-04-01
影响因子：
3.5
通讯作者：
Simplicio, Ana Luisa
中科院分区：
文献类型：
--
作者：
Serra, H.;Mendes, T.;Simplicio, Ana Luisa
使用细胞模型 Caco-2 以及人工膜模型 PAMPA 对三种糖基化黄酮类化合物（地奥司明、橙皮苷和柚皮苷）和各自的苷元的表观电离常数和双向渗透性进行了表征。通过毛细管电泳建立电离曲线。已证实大量糖苷配基在生理 pH 值下电离，而糖苷则呈中性形式。没有检测到糖苷在顶端到基底外侧或基底外侧到顶端方向的渗透，这证实了在通过肠膜吸收之前需要代谢。苷元在两个方向上渗透，表观渗透率 (P-app) 在 1-8 x 10(-5) cm/s 范围内。两种体外方法的结果相关，提供了一些被动转运的证据，但是不能排除主动转运的假设，特别是在香叶木丁的情况下。糖苷配基的代谢通过细胞模型进行检测，当加载到顶端时更广泛地检测到。通过酶水解，一些代谢物被鉴定为葡萄糖醛酸结合物。 (C) 2008 Elsevier Ltd. 保留所有权利。
Three glycosilated flavonoids (diosmin, hesperidin and naringin) and respective aglycones were characterized in terms of their apparent ionisation constants and bidirectional permeability using the cellular model Caco-2 as well as the artificial membrane model PAMPA. Ionisation curves were established by capillary electrophoresis. It was confirmed that significant amounts of the aglycones are ionised at physiological pH whereas the glycosides are in the neutral form. Permeation was not detected for the glycosides in either the apical to basolateral or basolateral to apical directions confirming the need for metabolism before absorption through the intestinal membrane. The aglycones permeated in both directions with apparent permeabilities (P-app) in the range of 1-8 x 10(-5) cm/s. The results from both in vitro methods correlated providing some evidence of passive transport however the hypothesis of active transport can not be excluded particularly in the case of diosmetin. Metabolism of the aglycones was detected with the cell model, more extensively when loading in the apical side. Some of the metabolites were identified as glucuronide conjugates by enzymatic hydrolysis. (C) 2008 Elsevier Ltd. All rights reserved.