Pregnane X receptor-mediated induction of Cyp3a by black cohosh.
作者： Xiaoyan Pang , Jie Cheng , Kristopher W. Krausz , De-an Guo , Frank J. Gonzalez
DOI: 10.3109/00498254.2010.527021
关键词: Black cohosh 、 Western blot 、 CYP3A4 、 Biology 、 In vivo 、 Pregnenolone 16α-carbonitrile 、 Endocrinology 、 Luciferase 、 Internal medicine 、 CYP3A 、 Pharmacology 、 Pregnane X receptor
摘要: Black cohosh (BC) has been widely applied for the treatment of menopausal symptoms. However, increasing concerns about herb-drug interactions demand need studies on influence BC cytochrome 450. Cyp3a11 in liver was induced by 7-fold wild-type mice treated with 500 mg/kg black 28 days compared control group as assessed quantitative real-time PCR; no difference found small intestine and kidney, suggesting that up-regulation liver-specific. Western blot, activity assays, pharmacokinetic analyses established dose- time-dependent induction Cyp3a11. To determine mechanism induction, including role pregnane X receptor (PXR) vivo vitro, respectively, Pxr-null, PXR-humanized, double transgenic CYP3A4/hPXR mice, cell-based luciferase assays were employed revealing mouse PXR played a direct Cyp3a11; human not activated cohosh. Overall, these findings demonstrate is liver-specific involved only PXR, counterpart. Thus, incidence interaction patients administered may be mediated CYP3A4.
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