游离蒽醌在人肠Caco-2细胞模型的转运(英文)

Intestinal Transport of Free Anthraquinones in Caco-2 Cell Model

目的:研究1,8-二羟基蒽醌(1,8-dihydroxyanthraquinone,DQ)、大黄酚(chrysophanol,CP)、大黄素(emodin,EN)、大黄酸(rhein,RN)、芦荟大黄素(aloe-emodin,AE)和ω-羟基大黄素(citreorosein,CN)在人肠Caco-2细胞单层模型的转运。方法:以人源Caco-2细胞单层为药物的肠吸收转运模型,将DQ、CP、EN、RN、AE和CN与其共温孵进行吸收转运,高效液相色谱法测定吸收转运量。结果:DQ、CP、EN、RN、AE和CN从顶侧(肠腔侧)向底侧(体循环侧)吸收转运的表观渗透系数(Papp)值分别为(2.16±0.38)×10-6、(3.00±0.09)×10-7、(1.99±0.94)×10-6、(4.58±0.20)×10-6、(6.24±0.19)×10-6和(7.34±0.61)×10-6cm.s-1;从底侧向顶侧吸收转运的Papp分别为(3.20±0.10)×10-6,(4.50±0.02)×10-7,(2.22±0.62)×10-6,(4.94±0.39)×10-6,(2.87±0.18)×10-6和(6.80±0.37)×10-6cm·s-1。DQ、EN、RN、AE和CN的Papp值比在Caco-2细胞单层模型上呈被动扩散机制、吸收良好的阳性对照化合物普萘洛尔的Papp值[(6.30±0.26)×10-5cm·s-1]小10倍,但比呈被动扩散机制、吸收不良的阳性对照化合物阿替洛尔的Papp值(<1×10-7cm.s-1)大10倍。CP的Papp值与阿替洛尔的Papp值基本上在同一数量级。ATP耗竭剂碘乙酰胺不影响AE在两个方向上的转运。结论:DQ、CP、EN、RN、AE和CN在人源Caco-2细胞单层模型的吸收转运机制为被动扩散;DQ、EN、RN、AE和CN属于中等吸收的化合物,CP属于吸收不良的化合物。

AIM： To investigate the transepithelial transport of the six free anthraquinones 1, 8-dihydroxyanthraquinone （DQ）, chrysophanol （CP）, emodin （EN）, rhein （RN）, aloe-emodin （AE） and citreorosein （CN） in the human intestinal Caco-2 cell monolayer model. METHODS： The monolayers of the human intestinal epithelial cancer cell line Caeo-2 were incubated with DQ, CP, EN, RN, AE and CN to model its intestinal absorption and transport, respectively. The determination of the compounds was performed by high-performance liquid chromatography. RESULTS： The apparent permeability coefficients （Papp,） in the Caco- 2 cell monolayers for DQ, CP, EN, RN, AE and CN were （2. 16±0.38） ×10 6, （3.00 ±0.09） × 10^-7, （1.994±0.94） × 10^-6, （4.58±0.20） × 10^-6, （6.24±0. 19） × 10^-6 and （7.34±0.61） × 10^-6cm.s^-1 from the apieal-to-basolateral direction, respectively, and（3.20±0.10） × 10^-6, （4.50± 0.02） × 10^-7, （2.22 ± 0.62） × 10^-6, （4.94± 0.39） × 10^-6, （2.87 ± 0. 18） × 10^-6 and （6.80 ± 0. 37） × 10^-6 cm.s^-1 from the basolateral-to-apical direction, respectively. The Papp values of DQ, EN, RN, AE and CN were about 10 times less than those [（6. 30 ± 0. 26） × 10^-5 cm.s^-1] of propranolol as a reference standard compound of high permeability and the main mechanism of intestinal absorption by passive diffusion, and about 10 times higher than those （ 〈 1 × 10^-7 cm.s^-1） of atenolol as a reference standard compound of poor permeability and the main mechanism of intestinal absorption by passive diffusion. Whereas, the Papp value of CP was at nearly the same magnitude with those of atenolol. In the presence of iodoacetamide, the Papp, of AE were not affected in both apical-to-basolateral and basolateral-to-apical directions. CONCLUSION： The intestinal absorption of all test compounds was passive diffusion as the dominating process in Caco-2 cell monolayer model. DQ, EN, RN, AE and CN will be moderately absorbed compounds and CP was estimated to be a poor- ly absorbed compound.