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题名: Strong inhibition of deoxyschizandrin and schisantherin A toward UDP-glucuronosyltransferase (UGT) 1A3 indicating UGT inhibition-based herb-drug interaction
作者: Liu, Cong1;  Cao, Yun-Feng2, 3, 4;  Fang, Zhong-Ze3, 4, 5;  Zhang, Yan-Yan3, 4;  Hu, Cui-Min5;  Sun, Xiao-Yu3, 4;  Huang, Ting2;  Zeng, Jia2;  Fan, Xu-Ran3, 4;  Hong, Mo3, 4
关键词: Deoxyschizandrin ;  UDP-glucuronosyltransferases (UGTs) ;  Herb-drug interaction
刊名: FITOTERAPIA
发表日期: 2012-12-01
DOI: 10.1016/j.fitote.2012.08.004
卷: 83, 期:8, 页:1415-1419
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Life Sciences & Biomedicine
类目[WOS]: Chemistry, Medicinal ;  Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
英文摘要: Deoxyschizandrin and schisantherin A are major bioactive lignans isolated from Fructus schisandrae which has been widely used as a tonic in traditional Chinese medicine for many years. Inhibition of UDP-glucuronosyltransferases (UGTs) by herbal components might be an important reason for clinical herb-drug interaction. The aim of the present study is to investigate the inhibitory effect of deoxyschizandrin and schisantherin A on major UGT isoforms. Recombinant UGT isoforms were used as enzyme source, and a nonspecific substrate 4-methylumbelliferone (4-MU) was utilized as substrate. The results showed that 100 mu M of deoxyschizandrin and schisantherin A exhibited strong inhibition on UGT1A3, and negligible inhibition on other tested UGT isoforms. Furthermore, deoxyschizandrin and schisantherin A were demonstrated to inhibit UGT1A3 in a concentration-dependent manner, with IC50 value of 10.8 +/- 0.4 mu M and 12.5 +/- 0.5 mu M, respectively. Dixon and Lineweaver-Burk plots showed that inhibition of UGT1A3 by deoxyschizandrin was best fit to competitive inhibition type, and inhibition kinetic parameter (KO was calculated to be 0.48 mu M. Inhibition of UGT1A3 by schisantherin A gave the best fit for types of noncompetitive inhibition, and the results showed K-i to be 11.3 mu M. All these experimental data suggested that herb-drug interaction might occur when deoxyschizandrin or schisantherin A containing herbs were co-administered with drugs which mainly undergo UGT1A3-mediated metabolism. However, given that many in vivo factors could influence the in vitro-in vivo extrapolation (IVIVE), these in vitro inhibitory parameters should be considered with caution. (C) 2012 Elsevier B.V. All rights reserved.
关键词[WOS]: LIVER CYTOCHROME-P450 ENZYMES ;  METABOLISM ;  EXTRACT ;  IDENTIFICATION ;  BIOACTIVATION ;  SCHIZANDRIN ;  CYP3A4
语种: 英语
WOS记录号: WOS:000312916400017
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/143017
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.China Med Univ, Shengjing Hosp, Dept Endocrinol, Shenyang 110004, Peoples R China
2.Shanghai Inst Planned Parenthood Res, Natl Populat & Family Planning Key Lab Contracept, Shanghai 200032, Peoples R China
3.Chinese Acad Sci, Dalian Inst Chem Phys, Joint Ctr Translat Med, Dalian 116023, Peoples R China
4.Liaoning Med Univ, Affiliated Hosp 1, Dalian 116023, Peoples R China
5.NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA

Recommended Citation:
Liu, Cong,Cao, Yun-Feng,Fang, Zhong-Ze,et al. Strong inhibition of deoxyschizandrin and schisantherin A toward UDP-glucuronosyltransferase (UGT) 1A3 indicating UGT inhibition-based herb-drug interaction[J]. FITOTERAPIA,2012,83(8):1415-1419.
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