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题名: Characterization of triptolide hydroxylation by cytochrome P450 in human and rat liver microsomes
作者: Li, W.1, 5;  Liu, Y.1;  He, Y. -Q.2;  Zhang, J. -W.1;  Gao, Y.3;  Ge, G. -B.1, 5;  Liu, H. -X.1, 5;  Huo, H.1;  Liu, H. -T.1, 5;  Wang, L. -M.3;  Sun, J.3;  Wang, Q.4;  Yang, L.1
通讯作者: 杨凌
关键词: Triptolide ;  cytochrome P450 ;  mono-hydroxylated metabolite
刊名: XENOBIOTICA
发表日期: 2008
DOI: 10.1080/00498250802503359
卷: 38, 期:12, 页:1551-1565
收录类别: SCI
文章类型: Article
部门归属: 18
项目归属: 1806
产权排名: 1;1
WOS标题词: Science & Technology ;  Life Sciences & Biomedicine
类目[WOS]: Pharmacology & Pharmacy ;  Toxicology
研究领域[WOS]: Pharmacology & Pharmacy ;  Toxicology
英文摘要: Triptolide, the primary active component of a traditional Chinese medicine Tripterygium wilfordii Hook F, has a wide range of pharmacological activities. In the present study, the metabolism of triptolide by cytochrome P450s was investigated in human and rat liver microsomes. Triptolide was converted to four metabolites (M-1, M-2, M-3, and M-4) in rat liver microsomes and three (M-2, M-3, and M-4) in human liver microsomes. All the products were identified as mono-hydroxylated triptolides by liquid chromatography-mass spectrometry (LC-MS). The studies with chemical selective inhibitors, complementary DNA-expressed human cytochrome P450s, correlation analysis, and enzyme kinetics were also conducted. The results demonstrate that CYP3A4 and CYP2C19 could be involved in the metabolism of triptolide in human liver, and that CYP3A4 was the primary isoform responsible for its hydroxylation.
关键词[WOS]: WILFORDII HOOK-F ;  TRIPTERYGIUM-WILFORDII ;  DRUG-METABOLISM ;  ENZYMES ;  TRIPDIOLIDE ;  CLEARANCE ;  TUMORS
语种: 英语
原文出处: 查看原文
WOS记录号: WOS:000261174400008
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/100901
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.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Peoples R China
2.Shanghai Univ Tradit Chinese Med, Shanghai, Peoples R China
3.Dalian Med Univ, Affiliated Hosp 2, Dalian, Peoples R China
4.Dalian Univ Technol, Dalian, Peoples R China
5.Chinese Acad Sci, Grad Univ, Beijing, Peoples R China

Recommended Citation:
Li, W.,Liu, Y.,He, Y. -Q.,et al. Characterization of triptolide hydroxylation by cytochrome P450 in human and rat liver microsomes[J]. XENOBIOTICA,2008,38(12):1551-1565.
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