天然和合成酚类化合物对小鼠肝脏细胞色素P450活性的抑制作用。

Inhibition of murine hepatic cytochrome P450 activities by natural and synthetic phenolic compounds.

Baer-Dubowska W, Szaefer H, Krajka-Kuzniak V

K. Marcinkowski University of Medical Sciences, Department of Pharmaceutical Biochemistry, Poznan, Poland.

Xenobiotica. 1998 Aug;28(8):735-43. doi: 10.1080/004982598239155.

Abstract

The effect of the phenolic compounds protocatechuic acid, chlorogenic acid, tannic acid, gallates and silybin on ethoxyresorufin O-dealkylase (CYP1A1), methoxyresorufin O-dealkylase (CYP1A2) and pentoxy-O-dealkylase (CYP2B) was examined in mouse liver microsomes from induced animals. 2. All compounds tested could inhibit cytochrome P450-mediated enzyme activities, but to different extents. Tannic acid was the most potent inhibitor, especially toward EROD activity with an IC50=2.6 microM. Synthetic dodecyl gallate was also relatively selective toward this enzyme activity with an IC50=120 microM. 3. Protocatechuic acid, chlorogenic and silybin were more selective towards PROD and MROD activities. Their relative inhibitory potency for PROD activity was as follows: chlorogenic acid > protocatechuic acid > silybin > dodecyl gallate > propyl gallate. Protocatechuic acid was a more effective inhibitor of MROD activity than chlorogenic acid, and propyl gallate more effective than dodecyl gallate. Thus, no clear structure-activity or selectivity relationship was observed. 4. Analysis of the kinetics of inhibition revealed that the inhibition in most cases was non-competitive in nature.

摘要

在诱导动物的小鼠肝微粒体中检测了酚类化合物原儿茶酸、绿原酸、单宁酸、没食子酸盐和水飞蓟宾对乙氧基异吩恶唑酮O-脱烷基酶（CYP1A1）、甲氧基异吩恶唑酮O-脱烷基酶（CYP1A2）和戊氧基-O-脱烷基酶（CYP2B）的影响。2. 所有测试的化合物都能抑制细胞色素P450介导的酶活性，但程度不同。单宁酸是最有效的抑制剂，尤其是对EROD活性，IC50=2.6微摩尔。合成十二烷基没食子酸盐对该酶活性也相对具有选择性，IC50=120微摩尔。3. 原儿茶酸、绿原酸和水飞蓟宾对PROD和MROD活性更具选择性。它们对PROD活性的相对抑制效力如下：绿原酸＞原儿茶酸＞水飞蓟宾＞十二烷基没食子酸盐＞丙基没食子酸盐。原儿茶酸对MROD活性的抑制作用比绿原酸更有效，丙基没食子酸盐比十二烷基没食子酸盐更有效。因此，未观察到明确的构效关系或选择性关系。4. 抑制动力学分析表明，在大多数情况下，抑制作用本质上是非竞争性的。