Zuo Zhong, Zhang Li, Zhou Limin, Chang Qi, Chow Moses
School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, SAR, PR China.
Life Sci. 2006 Nov 25;79(26):2455-62. doi: 10.1016/j.lfs.2006.08.014. Epub 2006 Aug 18.
Our previous studies identified hyperoside (HP), isoquercitrin (IQ) and epicatechin (EC) to be the major active flavonoid components of the hawthorn phenolic extract from hawthorn fruits demonstrating inhibitory effect on in vitro Cu(+2)-mediated low density lipoproteins oxidation. Among these three hawthorn flavonoids, EC was the only one detectable in plasma after the oral administration of hawthorn phenolic extract to rats. The present study aims to investigate the intestinal absorption mechanisms of these three hawthorn flavonoids by in vitro Caco-2 monolayer model, rat in situ intestinal perfusion model and in vivo pharmacokinetics studies in rats. In addition, in order to investigate the effect of the co-occurring components in hawthorn phenolic extract on the intestinal absorption of these three major hawthorn flavonoids, intestinal absorption transport profiles of HP, IQ and EC in forms of individual pure compound, mixture of pure compounds and hawthorn phenolic extract were studied and compared. The observations from in vitro Caco-2 monolayer model and in situ intestinal perfusion model indicated that all three studied hawthorn flavonoids have quite limited permeabilities. EC and IQ demonstrated more extensive metabolism in the rat in situ intestinal perfusion model and in vivo study than in Caco-2 monolayer model. Moreover, results from the Caco-2 monolayer model, rat in situ intestinal perfusion model as well as the in vivo pharmacokinetics studies in rats consistently showed that the co-occurring components in hawthorn phenolic extract might not have significant effect on the intestinal absorption of the three major hawthorn flavonoids studied.
我们之前的研究确定了金丝桃苷（HP）、异槲皮苷（IQ）和表儿茶素（EC）是山楂果实中酚类提取物的主要活性黄酮类成分，这些成分对体外铜（+2）介导的低密度脂蛋白氧化具有抑制作用。在这三种山楂黄酮类化合物中，给大鼠口服山楂酚类提取物后，血浆中仅能检测到EC。本研究旨在通过体外Caco-2单层模型、大鼠原位肠灌注模型以及大鼠体内药代动力学研究来探究这三种山楂黄酮类化合物的肠道吸收机制。此外，为了研究山楂酚类提取物中同时存在的成分对这三种主要山楂黄酮类化合物肠道吸收的影响，对HP、IQ和EC以单一纯化合物、纯化合物混合物以及山楂酚类提取物形式的肠道吸收转运情况进行了研究和比较。体外Caco-2单层模型和原位肠灌注模型的观察结果表明，所有三种研究的山楂黄酮类化合物的通透性都相当有限。与Caco-2单层模型相比，EC和IQ在大鼠原位肠灌注模型和体内研究中表现出更广泛的代谢。此外，Caco-2单层模型、大鼠原位肠灌注模型以及大鼠体内药代动力学研究的结果一致表明，山楂酚类提取物中同时存在的成分可能对所研究的三种主要山楂黄酮类化合物的肠道吸收没有显著影响。
