Identification of human UDP-glucuronosyltransferase isoforms involved in the isofraxidin glucuronidation and assessment of the species differences of the reaction
文献类型：期刊论文
| 作者 | Meng, Fanxing2; Li, Yan1; He, Guiyuan1; Ge, Guangbo1; Liu, Shumin2 |
| 刊名 | FITOTERAPIA
 |
| 出版日期 | 2017-03-01 |
| 卷号 | 117页码:118-125 |
| 关键词 | Isofraxidin Udp-glucuronosyltransferases (Ugts) Human Liver Microsomes (Hlm) Human Intestinal Microsomes (Him) Species Differences |
| ISSN号 | 0367-326X |
| DOI | 10.1016/j.fitote.2016.11.017 |
| 文献子类 | Article |
| 英文摘要 | Isofraxidin, 7-Hydroxy-6.8-dimethoxy-2H-1-benzopyran-2-one, is a major active component of Acanthopanax senticosus, which has been used as Acanthopanax (Ciwujia) injection to treat cardiovascular and cerebrovascular diseases in China for more than thirty years. The purpose of this study was to identify the roles of human UDP-glucuronosyltransferases (UGTs) in isofraxidin glucuronidation in the liver and intestinal microsomes and to reveal the potential species differences by comparing the liver microsomal glucuronidation from different experimental animals. One metabolite was biosynthesized and characterized as isofraxidin-7-O-glucuronide by liquid chromatography tandeirt mass spectrometry (LC-MS/MS) and nuclear magnetic resonance (NMR). The intrinsic clearances in human liver and intestinal microsomes were 63.8 and 16.4 mu L/min/mg, respectively. Human liver microsomes displays higher potential for isofraxidin elimination than human intestinal microsomes. The reaction phenotyping analysis Was conducted using cDNA-expressed human UGTs and chemical inhibitors. The results indicated that UGT1A1 and UGT1A9 were the main isoforms involved in the formation of isofraxidin-7-O-glucuronide. The isofraxidin glucuronidation in liver microsomes from human (HLM), rat (RLM), mouse (MLM), dog (DLM), monkey (CyLM), minipig (PLM), and guinea pig (GpLM) followed the Michealis-Menten model. The isofraxidin glucuronidation displays species differences in terms of catalytic activities. GpLM had the highest clearance with the CLint value of 152 mu L/min/mg. CyLM, RLM and MLM exhibit similar catalytic activities in isofraxidin glucuronidation with the intrinsic clearance values of 54.6, 58.0 and 50.2 mu L/min/mg, respectively, which are higher than those of PLM and DLM (23.9 and 37.7 mu L/min/mg, respectively). Rat exhibits the most similar intrinsic metabolic clearance (CLint) to human. (C) 2016 Published by Elsevier B.V. |
| WOS关键词 | IN-VITRO ; ACANTHOPANAX-SENTICOSUS ; MASS-SPECTROMETRY ; EXPRESSION ; METABOLISM ; RAT ; SELECTIVITY ; ENZYMES ; DOG ; 1A |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000395852600019 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/169348]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 通讯作者 | Liu, Shumin |
| 作者单位 | 1.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Peoples R China 2.Heilongjiang Univ Chinese Med, Inst Tradit Chinese Med, Drug Safety Evaluat Ctr, Chinese Med Toxicol Lab, Harbin 150040, Peoples R China |
| 推荐引用方式 GB/T 7714 | Meng, Fanxing,Li, Yan,He, Guiyuan,et al. Identification of human UDP-glucuronosyltransferase isoforms involved in the isofraxidin glucuronidation and assessment of the species differences of the reaction[J]. FITOTERAPIA,2017,117:118-125. |
| APA | Meng, Fanxing,Li, Yan,He, Guiyuan,Ge, Guangbo,&Liu, Shumin.(2017).Identification of human UDP-glucuronosyltransferase isoforms involved in the isofraxidin glucuronidation and assessment of the species differences of the reaction.FITOTERAPIA,117,118-125. |
| MLA | Meng, Fanxing,et al."Identification of human UDP-glucuronosyltransferase isoforms involved in the isofraxidin glucuronidation and assessment of the species differences of the reaction".FITOTERAPIA 117(2017):118-125. |
入库方式： OAI收割
来源：大连化学物理研究所
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