Identification of UDP-glucuronosyltransferase isoforms involved in hepatic and intestinal glucuronidation of phytochemical carvacrol

被引：16
作者：
Dong, Rui-Hua [2 ]
Fang, Zhong-Ze [1 ]
Zhu, Liang-Liang [1 ]
Ge, Guang-Bo [1 ]
Yang, Ling [1 ]
Liu, Ze-Yuan [2 ]
机构：
[1] Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Peoples R China
[2] Acad Mil Med Sci, Affiliated Hosp, Dept Clin Pharmacol, Beijing 100071, Peoples R China
来源：
XENOBIOTICA | 2012年 / 42卷 / 10期
基金：
中国国家自然科学基金;
关键词：
UDP-glucuronosyltransferase; carvacrol; human liver microsomes; human intestinal microsomes; LIVER CYTOCHROME-P450 ENZYMES; IN-VITRO; DRUG-GLUCURONIDATION; ANTIOXIDANT ACTIVITY; NOMENCLATURE UPDATE; GENE SUPERFAMILY; ESSENTIAL OILS; SUBSTRATE; THYMOL; XENOBIOTICS;
D O I：
10.3109/00498254.2012.682614
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
1. Carvacrol (2-methyl-5-(1-methylethyl)-phenol), one of the main components occurring in many essential oils of the family Labiatae, has been widely used in food, spice and pharmaceutical industries. 2. The carvacrol glucuronidation was characterized by human liver microsomes (HLMs), human intestinal microsomes (HIMs) and 12 recombinant UGT (rUGT) isoforms. 3. One metabolite was identified as a mono-glucuronide by liquid chromatography/mass spectrometry with HLMs, HIMs, rUGT1A3, rUGT1A6, rUGT1A7, rUGT1A9 and rUGT2B7. 4. The study with a chemical inhibition, rUGT, and kinetics study demonstrated that rUGT1A9 was the major isozyme responsible for glucuronidation in HLMs, and rUGT1A7 played a major role for glucuronidation in HIMs.
引用
收藏
页码：1009 / 1016
页数：8
相关论文
共 38 条
[1]   Characterization of catechol glucuronidation in rat liver [J].
Antonio, L ;
Grillasca, JP ;
Taskinen, J ;
Elovaara, E ;
Burchell, B ;
Piet, MH ;
Ethell, B ;
Ouzzine, M ;
Fournel-Gigleux, S ;
Magdalou, J .
DRUG METABOLISM AND DISPOSITION, 2002, 30 (02) :199-207
[2]   Effect of carvacrol on hepatic marker enzymes and antioxidant status in d-galactosamine-induced hepatotoxicity in rats [J].
Aristatile, Balakrishnan ;
Al-Numair, Khalid S. ;
Veeramani, Chinnadurai ;
Pugalendi, Kodukkur Viswanathan .
FUNDAMENTAL & CLINICAL PHARMACOLOGY, 2009, 23 (06) :757-765
[3]   METABOLISM IN RATS OF PARA-CYMENE DERIVATIVES - CARVACROL AND THYMOL [J].
AUSTGULEN, LT ;
SOLHEIM, E ;
SCHELINE, RR .
PHARMACOLOGY & TOXICOLOGY, 1987, 61 (02) :98-102
[4]  
Baser KHC, 2008, CURR PHARM DESIGN, V14, P3106, DOI 10.2174/138161208786404227
[5]   Isoform-selective probe substrates for in vitro studies of human UDP-glucuronosyltransferases [J].
Court, MH .
PHASE II CONJUGATION ENZYMES AND TRANSPORT SYSTEMS, 2005, 400 :104-116
[6]   Interindividual variability in hepatic drug glucuronidation: studies into the role of age, sex, enzyme inducers, and genetic polymorphism using the human liver bank as a model system [J].
Court, Michael H. .
DRUG METABOLISM REVIEWS, 2010, 42 (01) :209-224
[7]   Constituents of aromatic plants: carvacrol [J].
De Vincenzi, M ;
Stammati, A ;
De Vincenzi, A ;
Silano, M .
FITOTERAPIA, 2004, 75 (7-8) :801-804
[8]   Identification of Cytochrome P450 (CYP) Isoforms involved in the Metabolism of Corynoline, and Assessment of its Herb-Drug Interactions [J].
Fang, Zhong-Ze ;
Zhang, Yan-Yan ;
Ge, Guang-Bo ;
Liang, Si-Cheng ;
Sun, Dong-Xue ;
Zhu, Liang-Liang ;
Dong, Pei-Pei ;
Cao, Yun-Feng ;
Yang, Ling .
PHYTOTHERAPY RESEARCH, 2011, 25 (02) :256-263
[9]   Time-dependent inhibition (TDI) of CYP3A4 and CYP2C9 by noscapine potentially explains clinical noscapine-warfarin interaction [J].
Fang, Zhong-Ze ;
Zhang, Yan-Yan ;
Ge, Guang-Bo ;
Huo, Hong ;
Liang, Si-Cheng ;
Yang, Ling .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2010, 69 (02) :193-199
[10]  
Green MD, 1996, DRUG METAB DISPOS, V24, P356
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