Strong synergistic induction of CYP1A1 expression by andrographolide plus typical CYP1A inducers in mouse hepatocytes
Strong synergistic induction of CYP1A1 expression by andrographolide plus typical CYP1A inducers in mouse hepatocytes
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DOI：
10.1016/j.taap.2007.07.008
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发表时间：
2007-10-15
影响因子：
3.8
通讯作者：
Nemoto, Nobuo
中科院分区：
文献类型：
--
作者：
Jaruchotikamol, Atika;Jarukamjorn, Kanokwan;Nemoto, Nobuo
研究穿心莲的主要二萜成分穿心莲内酯对原代培养小鼠肝细胞细胞色素P450超家族成员细胞色素P450超家族成员细胞色素P1A1、细胞色素P1A2和细胞色素P1B1表达的影响以及对芳香烃受体(AhR)表达的影响，并与典型的细胞色素P1a诱导剂2，3，7，8-四氯二苯并对二恶英进行比较。穿心莲内酯能显著诱导细胞色素P1A1和细胞色素P1A2的mRNAs表达，并呈浓度依赖关系，与典型的细胞色素P1A1a诱导剂一样，穿心莲内酯不能诱导细胞色素P1A1和细胞色素P1A2的表达。有趣的是，穿心莲内酯和典型的CYP1A诱导剂协同诱导细胞色素P1A1的表达，这种协同作用被AhR拮抗剂白藜芦醇阻断。细胞色素P4501A1酶活性表现出类似的诱导模式。这是首次报道穿心莲内酯具有诱导细胞色素P1A1酶的活性，表明穿心莲内酯可能是一种非常有用的化合物，可用于研究细胞色素P1A1诱导途径的调节机制。此外，我们的发现表明，根据其诱导细胞色素PYP1A1表达的能力，为合理给药提供建议。(C)2007 Elsevier Inc.保留所有权利。
The effects of andrographolide, the major diterpenoid constituent of Andrographis paniculata, on the expression of cytochrome P450 superfamily 1 members, including CYP1A1, CYP1A2, and CYP1B1, as well as on aryl hydrocarbon receptor (AhR) expression in primary cultures of mouse hepatocytes were investigated in comparison with the effects of typical CYP1A inducers, including benz[a]anthracene, beta-naphthoflavone, and 2,3,7,8-tetrachlorodibenzo-p-dioxin. Andrographolide significantly induced the expression of CYP1A1 and CYP1A2 mRNAs in a concentration-dependent manner, as did the typical CYP1A inducers, but did not induce that of CYP1B1 orAhR. Interestingly, andrographolide plus the typical CYP1A inducers synergistically induced CYP1A1 expression, and the synergism was blocked by an AhR antagonist, resveratrol. The CYP1A1 enzyme activity showed a similar pattern of induction. This is the first report that shows that andrographolide has a potency to induce CYP1A1 enzyme and indicates that andrographolide could be a very useful compound for investigating the regulatory mechanism of the CYP1A1 induction pathway. In addition, our findings suggest preparing advice for rational administration of A.paniculata, according to its ability to induce CYP1A1 expression. (C) 2007 Elsevier Inc. All rights reserved.