Hamada Mika, Satsu Hideo, Natsume Yayoi, Nishiumi Shin, Fukuda Itsuko, Ashida Hitoshi, Shimizu Makoto
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Yayoi, Bunkyo-ku, 113-8657, Japan.
J Agric Food Chem. 2006 Nov 15;54(23):8891-8. doi: 10.1021/jf060944t.
Since the toxicological effects of dioxins are mainly mediated by the aryl hydrocarbon receptor (AhR), an in vitro assessment system for AhR activity was used in this study to search for flavonoids that attenuated dioxin toxicity through the intestinal epithelial monolayer. When AhR transformation in Hepa-1c1c7 cells was examined by southwestern ELISA, nine flavonoids among 34 kinds of flavonoids inhibited the transformation by more than one-half. When each flavonoid with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was added to dioxin-responsive HepG2 cells, seven flavonoids significantly restrained the TCDD-induced transcriptional activity of the CYP1A1 promoter. Furthermore, those seven flavonoids that had permeated the Caco-2 cell monolayers demonstrated an inhibitory effect on both the AhR transformation and on the transcriptional activity of the CYP1A1 promoter. The expression level of the CYP1A1 mRNA and protein induced by TCDD was suppressed by flavone, galangin, and tangeretin. It is proposed from these results that some flavonoids have the ability to suppress dioxin-induced AhR activity after permeating the human intestinal epithelial cell monolayer.
由于二噁英的毒理学效应主要由芳烃受体（AhR）介导，本研究使用了一种AhR活性的体外评估系统，以寻找通过肠上皮单层减弱二噁英毒性的黄酮类化合物。当通过western ELISA检测Hepa-1c1c7细胞中的AhR转化时，34种黄酮类化合物中有9种抑制转化率超过一半。当将每种黄酮类化合物与2,3,7,8-四氯二苯并对二噁英（TCDD）添加到二噁英反应性HepG2细胞中时，7种黄酮类化合物显著抑制了TCDD诱导的CYP1A1启动子的转录活性。此外，那些渗透过Caco-2细胞单层的7种黄酮类化合物对AhR转化和CYP1A1启动子的转录活性均表现出抑制作用。黄酮、高良姜素和橘皮素抑制了TCDD诱导的CYP1A1 mRNA和蛋白质的表达水平。从这些结果推测，一些黄酮类化合物在渗透人肠上皮细胞单层后具有抑制二噁英诱导的AhR活性的能力。
