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题名: Glucuronidation of bavachinin by human tissues and expressed UGT enzymes: Identification of UGT1A1 and UGT1A8 as the major contributing enzymes
作者: Lv, Xia1, 2;  Hou, Jie3;  Xia, Yang-Liu2;  Ning, Jing2, 3;  He, Gui-Yuan2;  Wang, Ping2;  Ge, Guang-Bo2;  Xiu, Zhi-Long1;  Yang, Ling2
关键词: Bavachinin ;  UDP-glucuronosyltransferases ;  UGT1A1 ;  UGT1A8 ;  Glucuronidation ;  Human tissues
刊名: DRUG METABOLISM AND PHARMACOKINETICS
发表日期: 2015-10-01
DOI: 10.1016/j.dmpk.2015.07.001
卷: 30, 期:5, 页:358-365
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Life Sciences & Biomedicine
类目[WOS]: Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
英文摘要: Bavachinin (BCI), a major bioactive compound in Chinese herbal Psoralea corylifolia, possesses a wide range of biological activities. In this study, the glucuronidation pathway of BCI was characterized for the first time, by using pooled human liver microsomes (HLM), pooled human intestine microsomes (HIM) and recombinant human UDP-glucosyltransferases (UGTs). One mono-glucuronide was detected in HLM in the presence of uridine-diphosphate glucuronic acid (UDPGA), and it was biosynthesized and well-characterized as BCI-4'-O-glucuronide (BCIG). Reaction phenotyping assay showed that UGT1A1, UGT1A3 and UGT1A8 were involved in BCI-4'-O-glucuronidation, while UGT1A1 and UGT1A8 displayed the higher catalytic ability among all tested UGT isoforms. Kinetic analysis demonstrated that BCI-4'-O-glucuronidation in both HLM and UGT1A1 followed sigmoidal kinetic behaviors and displayed much close Km values (12.4 mu M in HLM & 9.7 mu M in UGT1A1). Both chemical inhibition assays and correlation analysis demonstrated that UGT1A1 displayed a predominant role in BCI-4'-O-glucuronidation in HLM. Both HIM and UGT1A8 exhibited substrate inhibition at high concentrations, and Km values of HIM and UGT1A8 were 3.6 and 2.3 mM, respectively. Similar catalytic efficiencies were observed for HIM (199.3 mu L/min/mg) and UGT1A8 (216.2 mL/min/mg). These findings suggested that UGT1A1 and UGT1A8 were the primary isoforms involved in BCI-4'-O-glucuronidation in HLM, and HIM, respectively. Copyright (C) 2015, The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.
关键词[WOS]: UDP-GLUCURONOSYLTRANSFERASE ISOFORMS ;  HUMAN LIVER ;  PSORALEA-CORYLIFOLIA ;  IN-VITRO ;  LIQUID-CHROMATOGRAPHY ;  ACID ;  INTESTINE ;  MAGNOLOL ;  POTENT ;  SEEDS
语种: 英语
WOS记录号: WOS:000362974900006
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/146597
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.Dalian Univ Technol, Dept Biosci & Biotechnol, Dalian, Peoples R China
2.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian, Peoples R China
3.Dalian Med Univ, Dalian, Peoples R China

Recommended Citation:
Lv, Xia,Hou, Jie,Xia, Yang-Liu,et al. Glucuronidation of bavachinin by human tissues and expressed UGT enzymes: Identification of UGT1A1 and UGT1A8 as the major contributing enzymes[J]. DRUG METABOLISM AND PHARMACOKINETICS,2015,30(5):358-365.
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