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题名: Tissue and species differences in the glucuronidation of glabridin with UDP-glucuronosyltransferases
作者: Guo, Bin1, 3, 4;  Fang, Zhongze2, 3, 4;  Yang, Lu3, 4;  Xiao, Ling5;  Xia, Yangliu6;  Gonzalez, Frank J.7;  Zhu, Liangliang5;  Cao, Yunfeng3, 4, 8;  Ge, Guangbo6;  Yang, Ling6;  Sun, Hongzhi1
关键词: Glabridin ;  Glucuronidation ;  UDP-glucuronosyltransferases ;  Species differences
刊名: CHEMICO-BIOLOGICAL INTERACTIONS
发表日期: 2015-04-25
DOI: 10.1016/j.cbi.2015.03.001
卷: 231, 页:90-97
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Life Sciences & Biomedicine
类目[WOS]: Biochemistry & Molecular Biology ;  Pharmacology & Pharmacy ;  Toxicology
研究领域[WOS]: Biochemistry & Molecular Biology ;  Pharmacology & Pharmacy ;  Toxicology
英文摘要: Glabridin (GA) has gained wide application in the cosmetics and food industry. This study was performed to investigate its metabolic inactivation and elimination by glucuronidation by use of liver and intestine microsomes from humans (HLM and HIM) and rats (RLM and RIM), and liver microsomes from cynomolgus monkeys and beagle dogs (CyLM and DLM). Both hydroxyl groups at the C2 and C4 positions of the B ring are conjugated to generate two mono-glucuronides (M1 and M2). HIM, RIM and RLM showed the most robust activity in catalyzing M2 formation with intrinsic clearance values (Cl-int) above 2000 mu L/min/mg, with little measurable M1 formation activity. DLM displayed considerable activity both in M1 and M2 formation, with Cl-int values of 71 and 214 mu L/min/mg, respectively, while HLM and CyLM exhibited low activities in catalyzing M1 and M2 formation, with Cl-int values all below 20 mu L/min/mg. It is revealed that UGT1A1, 1A3, 1A9, 2B7, 2B15 and extrahepatic UGT1A8 and 1A10 are involved in GA glucuronidation. Nearly all UGTs preferred M2 formation except for UGT1A1. Notably, UGT1A8 displayed the highest activity with a Cl-int value more than 5-fold higher than the other isoforms. Chemical inhibition studies, using selective inhibitors of UGT1A1, 1A9, 2B7 and 1A8, further revealed that UGT1A8 contributed significantly to intestinal GA glucuronidation in humans. In summary, this in vitro study demonstrated large species differences in GA glucuronidation by liver and intestinal microsomes, and that intestinal UGTs are important for the pathway in humans. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
关键词[WOS]: TANDEM MASS-SPECTROMETRY ;  MESSENGER-RNA EXPRESSION ;  ISOFLAVAN GLABRIDIN ;  CYNOMOLGUS MONKEY ;  1A ISOFORMS ;  INHIBITION ;  ENZYMES ;  LIVER ;  SELECTIVITY ;  ABSORPTION
语种: 英语
WOS记录号: WOS:000353741100011
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/146227
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Liaoning Med Univ, Affiliated Hosp 1, Jinzhou, Peoples R China
2.Tianjin Med Univ, Sch Publ Hlth, Dept Toxicol, Tianjin, Peoples R China
3.Chinese Acad Sci, Dalian Inst Chem Phys, Joint Ctr Translat Med, Dalian, Peoples R China
4.Liaoning Med Univ, Affiliated Hosp 1, Dalian, Peoples R China
5.Anqing Normal Univ, Sch Life Sci, Ctr Drug & Food Safety Evaluat, Anqing 246011, Peoples R China
6.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian, Peoples R China
7.NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
8.Shanghai Inst Planned Parenthood Res, Shanghai Engineer & Technol Res Ctr Reprod Hlth D, Key Lab Contracept & Devices Res NPFPC, Shanghai, Peoples R China

Recommended Citation:
Guo, Bin,Fang, Zhongze,Yang, Lu,et al. Tissue and species differences in the glucuronidation of glabridin with UDP-glucuronosyltransferases[J]. CHEMICO-BIOLOGICAL INTERACTIONS,2015,231:90-97.
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