Transport and metabolism of ferulic acid through the colonic epithelium
Transport and metabolism of ferulic acid through the colonic epithelium
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DOI：
10.1124/dmd.107.017558
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发表时间：
2008-01-01
影响因子：
3.9
通讯作者：
Williamson, Gary
中科院分区：
文献类型：
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作者：
Poquet, Laure;Clifford, Michael N.;Williamson, Gary
阿魏酸是一种重要的抗氧化剂，存在于食品、饮料、补充剂和草药中。然而，其在结肠中的吸收机制从未被研究过，即使这是其体内吸收的主要部位。阿魏酸以游离形式有效转运通过由共培养的Caco-2和产粘液的HT 29-MTX细胞组成的结肠上皮体外模型，仅少量以阿魏酰-葡糖苷酸或硫酸盐形式转运，以及一些游离的二氢阿魏酸。使用大鼠外翻的升结肠囊和降结肠囊也观察到这种代谢和渗透模式。在细胞模型中，游离阿魏酸通过被动扩散渗透，如通过摄取随时间的线性和非饱和浓度依赖性所判断的。的渗透是独立的紧密连接，但强烈的疏水性的不同的酚酸测试，表明跨细胞，而不是细胞旁运输。使用抑制剂，我们发现只有一小部分（< 20%）的游离阿魏酸转运是载体介导的。3-[[ 3-[2-（7-氯喹啉-2-基）乙烯基]苯基]-（2-二甲基氨基甲酰基乙基硫基）甲硫基]丙酸（MK 571）降低了基底室中代谢物的产生，而环孢菌素A增加了代谢物的产生，这意味着多药耐药蛋白和P-糖蛋白转运蛋白参与了代谢物分别向浆膜侧和管腔侧的外排。这些结果表明，在穿过结肠屏障后，血液中可用的阿魏酸形式主要是游离形式，只有小百分比的共轭和还原的阿魏酸。
Ferulic acid is an important antioxidant found in food, beverages, supplements, and herbal medicines. However, its mechanism of absorption in the colon has never been examined, even though this is its main site of in vivo absorption. Ferulic acid was efficiently transported as the free form through an in vitro model for the colonic epithelium consisting of cocultured Caco-2 and mucus-producing HT29-MTX cells, with only a small amount transported as feruloyl-glucuronide or sulfate, together with some free dihydroferulic acid. This pattern of metabolism and permeation was also seen with the use of rat everted ascending and descending colon sacs. In the cell model, free ferulic acid permeated by passive diffusion, as judged by the linearity of the uptake over time and nonsaturable concentration dependence. The permeation was independent of tight junctions but strongly linked to the hydrophobicity of the different phenolic acids tested, suggesting a transcellular rather than a paracellular transport. Using inhibitors, we showed that only a small proportion (< 20%) of the free ferulic acid transport was carrier-mediated. The production of metabolites in the basal chamber was lowered by 3-[[ 3-[2-(7-chloroquinolin-2-yl)vinyl] phenyl]-(2-dimethylcarbamoylethylsulfanyl) methylsulfanyl] propionic acid (MK571) and increased by cyclosporin A, implying an involvement of multidrug resistance protein and P-glycoprotein transporters in the efflux of metabolites, respectively to the serosal and luminal sides. These results show that the form of ferulic acid available to the blood after passage across the colonic barrier would be mainly the free form, together with only a small percentage of conjugated and reduced ferulic acid.