Potent inhibitory effect of alpha-viniferin on human cytochrome P450

被引：16

作者：

Sim, Juhee ^{[1
]}

Jang, Hae Wring ^{[1
]}

Song, Min ^{[1
]}

Kim, Ji Hyang ^{[2
]}

Lee, Seung Ho ^{[2
]}

Lee, Sangkyu ^{[1
]}

机构：

[1] Kyungpook Natl Univ, Pharmaceut Sci Res Inst, Coll Pharm, Taegu 702701, South Korea

[2] Yeungnam Univ, Coll Pharm, Kyongsan 712749, South Korea

来源：

FOOD AND CHEMICAL TOXICOLOGY | 2014年 / 69卷

基金：

新加坡国家研究基金会;

关键词：

Alpha-viniferin; Cytochrome P450; Inhibition; Interaction; Human liver microsomes; IN-VITRO INHIBITION; DRUG-INTERACTIONS; RESVERATROL; METABOLISM; LIVER; RATS; SYNTHASE; CYP3A; ROOT;

D O I：

10.1016/j.fct.2014.04.023

中图分类号：

TS2 [食品工业];

学科分类号：

0832 ;

摘要：

alpha-Viniferin isolated from Caragana chamlagu is a trimer of resveratrol, and has several biological activities, which include anti-inflammatory, anti-oxidant, anti-arthritis, and anti-tumor activities. Herb-drug interactions are the source of the most harmful complications in patients coadministered herbal and modern medicines, and are caused by modulation of the activities of drug metabolizing enzymes. Here, the authors investigated the inhibitory effects of alpha-viniferin on the activities of 9 human cytochrome P450 (CYP) isoforms using a cocktail of probe substrates and LC-MS/MS in pooled human liver microsomes (HLMs). alpha-Viniferin strongly inhibited 7 of the 9 CYP isoforms (except CYP2A6 and CYP2E1). Furthermore, alpha-viniferin strongly inhibited CYP2C19-mediated omeprazole 5-hydroxylation and CYP3A4-catalyzed midazolam 1-hydroxylation with IC50 values of 0.93 and 1.2 mu M, respectively. cc-Viniferin strongly inhibited the activities of these two CYPs dose dependently, but not time-dependently. Lineweaver-Burk plots and secondary plots indicated a typical pattern of mix-mode inhibition for CYP2C19 and 3A4. This is the first investigation conducted on the inhibitory effect of alpha-viniferin on CYP2C19 and 3A4 in HLMs to predict a potential herb-drug interaction. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：276 / 280

页数：5

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