Inhibition of cytochrome P450 activities by oleanolic acid and ursolic acid in human liver microsomes
Inhibition of cytochrome P450 activities by oleanolic acid and ursolic acid in human liver microsomes
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DOI：
10.1016/j.lfs.2003.10.020
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发表时间：
2004-04-16
期刊：
影响因子：
6.1
通讯作者：
Lim, S
中科院分区：
文献类型：
--
作者：
Kim, KA;Lee, JS;Lim, S
利用人肝微粒体检测了具有抗炎、抗癌、保肝等多种药理活性的三萜酸类化合物油酸（OA）和熊果酸（UA）对几种细胞色素P450（CYP）酶活性的调节能力。OA竞争性抑制CYP 1A 2-催化的非那西丁O-脱乙基和CYP 3A 4-催化的咪达唑仑1-羟基化（主要的人体药物代谢CYP），IC 50（Ki）值分别为143.5（74.2）μ M和78.9（41.0）μ M。UA竞争性抑制CYP 2CI 9催化的S-美芬妥英4 '-羟基化，IC 50（Ki）值为119.7（80.3）μ M。然而，其他CYP测试显示没有或弱抑制OA和UA。目前的研究表明，OA和UA对人肝微粒体的β-淀粉样蛋白异构体具有抑制作用。因此，当与主要通过β-受体亚型代谢的药物同时使用时，食用含有OA或UA的草药或给予OA或UA可能会引起人体内的药物相互作用。此外，OA对CYP 1A 2的抑制作用似乎部分与其抗炎和抗癌活性有关。(C)2004年爱思唯尔公司All rights reserved.
Oleanolic acid (OA) and ursolic acid (UA), triterpene acids having numerous pharmacological activities including, anti-inflammatory, anti-cancer, and hepato-protective effects, were tested for their ability to modulate the activities of several cytochrome P450 (CYP) enzymes using human liver microsomes. OA competitively inhibited CYP1A2-catalyzed phenacetin O-deethylation and CYP3A4-catalyzed midazolam 1-hydroxylation, the major human drug metabolizing CYPs, with IC50 (K-i) values of 143.5 (74.2) muM and 78.9 (41.0) muM, respectively. UA competitively inhibited CYP2CI9-catalyzed S-mephenytoin 4'-hydroxylation with an IC50 (K-i) value of 119.7 (80.3) muM. However, other CYPs tested showed no or weak inhibition by both OA and UA. The present study demonstrates that OA and UA have inhibitory effects on CYP isoforms using human liver microsomes. It is thus likely that consumption of herbal medicines containing OA or UA, or administration of OA or UA, can cause drug interactions in humans when used concomitantly with drugs that are metabolized primarily by CYP isoforms. In addition, it appears that the inhibitory effect of OA on CYP1A2 is, in part, related to its anti-inflammatory and anticancer activities. (C) 2004 Elsevier Inc. All rights reserved.