Flavonoids alter P-gp expression in intestinal epithelial cells in vitro and in vivo
Flavonoids alter P-gp expression in intestinal epithelial cells in vitro and in vivo
复制标题
DOI：
10.1002/mnfr.200600225
复制
发表时间：
2007-03-01
影响因子：
5.2
通讯作者：
Wenzel, Uwe
中科院分区：
文献类型：
--
作者：
Lohner, Katrin;Schnaebele, Kerstin;Wenzel, Uwe
类黄酮是我们饮食中包含的次生植物代谢物，但也存在于越来越多的补充剂中。它们被认为与肠道运输系统相互作用，包括磷酸糖蛋白（P-gp），它介导各种异生物质回流到肠腔。在人肠道 Caco-2 细胞中，我们测试了 14 种不同的黄酮类化合物对体外 P-gp 表达的影响。通过蛋白质印迹、流式细胞术和实时 PCR 定量蛋白质表达水平。在蛋白质印迹实验中，当细胞暴露于化合物超过 4 周时，除芹菜素外，所有浓度为 10 μM 的黄酮类化合物都会增加 P-gp 的表达。黄酮是 Caco-2 细胞中最有效的 P-gp 诱导剂之一，因此，还评估了 C57BL/6 小鼠胃肠道体内 P-gp 变化的影响。黄酮（400 mg/kg 体重 x 天，持续 4 周）可显着增加小肠中的 P-gp 表达，但结肠中的 P-gp 表达没有增加，而结肠中的表达水平本质上最高。总之，黄酮类化合物在体外和体内引起肠上皮细胞中 P-gp 表达的增加可能作为限制亲脂性外源物进入生物体的适应和防御机制。
Flavonoids are secondary plant metabolites included in our diet but are also provided in a growing number of supplements. They are suggested to interact with intestinal transport systems including phospbo-glycoprotein (P-gp) which mediates the efflux of a variety of xenobiotics back into the gut lumen. In human intestinal Caco-2 cells, we tested the effects of 14 different flavonoids on P-gp expression in vitro. Protein expression levels were quantified by Western blotting, flow cytometry, and real-time PCR. Except apigenin, all flavonoids at concentrations of 10 mu M increased P-gp expression in Western blotting experiments when cells were exposed to the compounds over 4 wk. Flavone was one of the most effective P-gp inducers in Caco-2 cells and its effects were, therefore, also assessed for changes in P-gp in vivo in the gastrointestinal tract of C57BL/6 mice. P-gp expression was significantly increased by flavone (400 mg/kg body weight x day over 4 wk) in the small intestine but not in the colon which displayed intrinsically the highest expression level. In conclusion, the increase in P-gp expression caused by flavonoids in intestinal epithelial cells in vitro and also in vivo may serve as an adaptation and defense mechanism limiting the entry of lipophilic xenobiotics into the organism.