Identification and Characterization of Human UDP-glucuronosyltransferases Responsible for the Glucuronidation of Fraxetin
文献类型：期刊论文
| 作者 | Xia, Yang-Liu1,2; Liang, Si-Cheng1,2; Zhu, Liang-Liang1; Ge, Guang-Bo1; He, Gui-Yuan1,2; Ning, Jing1; Lv, Xia1; Ma, Xiao-Chi3; Yang, Ling1; Yang, Sheng-Li1 |
| 刊名 | drug metabolism and pharmacokinetics
 |
| 出版日期 | 2014-04-25 |
| 卷号 | 29期号:2页码:135-140 |
| 关键词 | fraxetin UDP-glucuronosyltransferases (UGTs) UGT1A9 glucuronidation human liver microsomes (HLMs) |
| 通讯作者 | 葛广波 |
| 英文摘要 | fraxetin, a major constituent of the traditional medicine plant fraxinus rhynchophylla hance (oleaceae), has been found to possess multiple bioactivities. however, the metabolic pathway(s) of fraxetin in human tissues has not been reported yet. this study aimed to characterize the glucuronidation pathway(s) of fraxetin in human tissues. fraxetin could be metabolized to two glucuronides in human liver microsomes (hlms). these two glucuronides were biosynthesized and characterized as 7-o-glucuronide (7-o-g) and 8-o-glucuronide (8-o-g). ugt1a1, -1a6, -1a7, -1a8, -1a9 and -1a10 participated in the formation of 7-o-g, while the formation of 8-o-g was catalyzed selectively by ugt1a6 and ugt1a9. ugt1a9 showed the highest catalytic activities in the formation of 7-o-g and 8-o-g. both kinetic characterization and inhibition assays demonstrated that ugt1a9 played important roles in fraxetin glucuronidations in hlms, especially in the formation of the major metabolite 8-o-g. furthermore, the intrinsic clearance of fraxetin in both human liver microsomes and ugt1a9 was greater than that of 7,8-dihydroxylcoumarin, revealing that the addition of a c-6 methoxy group led to the higher metabolic clearance. in summary, the glucuronidation pathways of fraxetin in human liver microsomes were well-characterized, and ugt1a9 was the major isoform responsible for the glucuronidations of fraxetin. |
| WOS标题词 | science & technology ; life sciences & biomedicine |
| 学科主题 | 物理化学 |
| 类目[WOS] | pharmacology & pharmacy |
| 研究领域[WOS] | pharmacology & pharmacy |
| 关键词[WOS] | human liver ; rats ; chromatography ; inhibition ; metabolism ; microsomes ; kidney ; mice |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000334596600005 |
| 公开日期 | 2016-05-09 |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/144431]  |
| 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 |
| 作者单位 | 1.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian, Peoples R China 2.Chinese Acad Sci, Grad Univ, Beijing, Peoples R China 3.Dalian Med Univ, Dalian, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xia, Yang-Liu,Liang, Si-Cheng,Zhu, Liang-Liang,et al. Identification and Characterization of Human UDP-glucuronosyltransferases Responsible for the Glucuronidation of Fraxetin[J]. drug metabolism and pharmacokinetics,2014,29(2):135-140. |
| APA | Xia, Yang-Liu.,Liang, Si-Cheng.,Zhu, Liang-Liang.,Ge, Guang-Bo.,He, Gui-Yuan.,...&Yang, Sheng-Li.(2014).Identification and Characterization of Human UDP-glucuronosyltransferases Responsible for the Glucuronidation of Fraxetin.drug metabolism and pharmacokinetics,29(2),135-140. |
| MLA | Xia, Yang-Liu,et al."Identification and Characterization of Human UDP-glucuronosyltransferases Responsible for the Glucuronidation of Fraxetin".drug metabolism and pharmacokinetics 29.2(2014):135-140. |
入库方式： OAI收割
来源：大连化学物理研究所
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