五味子素A和五味子素B对CYP3A活性的抑制作用。

Methods and findings in experimental and clinical pharmacology Pub Date : 2010-04-01 DOI:10.1358/mf.2010.32.3.1434161

W L Li, H W Xin, M W Su, L Xiong

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引用次数: 22

摘要

我们的目的是研究五味子素A和五味子素B对大鼠肝微粒体细胞色素P450 (CYP3A)活性的抑制作用及其相互作用机制。采用高效液相色谱法对1′-羟基咪达唑仑和CYP3A催化咪达唑仑1-羟基化反应进行了分析。结果表明，五味子素A和五味子素B抑制CYP3A活性的IC(50)值分别为6.60和5.51 microM, K(i)值分别为5.83和4.24 microM。每种抑制剂的稀释试验图的斜率值高达对照样品的91%。发现五味子甲素和五味子甲素B对CYP3A活性的失活具有时间和浓度依赖性(五味子甲素A: K(I) = 4.51 μ m, K(inact) = 0.134/min;五味子素B: K(I) = 3.01 μ m, K(inact) = 0.112/min。我们得出结论，五味子甲素和五味子甲素B对大鼠肝微粒体CYP3A活性的抑制主要是由于混合的非竞争性和完全抑制。

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Inhibitory effects of schisandrin A and schisandrin B on CYP3A activity.

Our aim was to investigate the inhibitory effects of schisandrin A and schisandrin B on cytochrome P450 (CYP3A) activity in rat liver microsomes and the mechanism of this interaction. 1'-Hydroxy midazolam and midazolam 1-hydroxylation catalyzed by CYP3A were analyzed by high performance liquid chromatography (HPLC). Results showed that schisandrin A and schisandrin B inhibited CYP3A activity with IC(50) values of 6.60 and 5.51 microM and K(i) values of 5.83 and 4.24 microM, respectively. A dilution assay plot of each inhibitor gave a slope value of up to 91% that of the control samples. The inactivation of CYP3A activity by schisandrin A and schisandrin B was found to be both time-and concentration-dependent (schisandrin A: K(I) = 4.51 microM, K(inact) = 0.134/min; schisandrin B: K(I) = 3.01 microM, K(inact) = 0.112/min). We conclude that the inhibition of CYP3A activity in rat liver microsomes by schisandrin A and schisandrin B is mostly attributed to a mixed noncompetitive and complete inhibition.

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来源期刊

Methods and findings in experimental and clinical pharmacology 医学-药学

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>12 weeks