Aryl hydrocarbon receptor-mediated induction of microsomal drug-metabolizing enzyme activity by indirubin and indigo
Aryl hydrocarbon receptor-mediated induction of microsomal drug-metabolizing enzyme activity by indirubin and indigo
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DOI：
10.1016/j.bbrc.2004.04.066
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发表时间：
2004-05-28
影响因子：
3.1
通讯作者：
Matsuda, T
中科院分区：
文献类型：
--
作者：
Sugihara, K;Kitamura, S;Matsuda, T
靛玉红和靛蓝。其被认为是芳烃受体（AhR）的天然配体，在使用重组酵母的报道基因测定中显示出显著的AhR配体活性。它们的活性与2，3，7，8-四氯二苯并-对-二恶英相当或更强。当靛玉红和靛蓝给予小鼠，乙氧基试卤灵-O-脱烷基酶和甲氧基试卤灵-O-脱烷基酶活性在肝脏中增加，但随后在2天内下降。靛玉红比靛蓝更有效。细胞色素P450 1A 1/2蛋白和mRNA在小鼠肝脏中的水平与靛玉红剂量也增加。在AhR基因敲除小鼠中未观察到靛玉红和靛蓝的这些增强作用。靛玉红或靛蓝可增强大鼠肝细胞和HepG 2细胞中的乙氧基试卤灵-O-脱烷基酶和甲氧基试卤灵-O-脱烷基酶活性，但其作用弱于2，3，7，8-四氯二苯并-p-二恶英。靛蓝胭脂红，靛蓝的硫酸盐衍生物，用作食品添加剂。没有显示出对药物代谢酶的这些诱导作用。我们的研究结果表明，靛玉红和靛蓝作为诱导剂细胞色素P450 1A 1/2介导的AhR在哺乳动物体内。(C)2004年爱思唯尔公司All rights reserved.
Indirubin and indigo. which are thought to be natural ligands for aryl hydrocarbon receptor (AhR), showed marked AhR ligand activities in a reporter gene assay using recombinant yeast. Their activities were comparable with or more potent than that of 2,3,7,8-tetrachlorodibenzo-p-dioxin. When indirubin and indigo were administered to mice, ethoxyresorufin-O-dealkylase and methoxyresorufin-O-dealkylase activities in the liver were increased, but subsequently decreased within 2 days. Indirubin was more potent than indigo. Levels of cytochrome P450 1A1/2 proteins and mRNAs in the liver of mice dosed with indirubin were also enhanced. These enhancing effects of indirubin and indigo were not observed in AhR knock-out mice. Ethoxyresorufin-O-dealkylase and methoxyresorufin-O-dealkylase activities in rat hepatocytes and HepG2 cells were enhanced by the addition of indirubin or indigo, but less potently than by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Indigocarmine, a sulfate derivative of indigo, which is used as food additive. did not show these inducing effects on drug-metabolizing enzymes. Our results suggest that indirubin and indigo act as inducers for cytochrome P450 1A1/2 mediated by AhR in mammals in vivo. (C) 2004 Elsevier Inc. All rights reserved.