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题名: The Inhibition of UDP-Glucuronosyltransferase (UGT) Isoforms by Praeruptorin A and B
作者: Liu, Xin1;  Chen, Da-Wei2;  Wu, Xue3, 4;  Zhao, Zhenying5;  Fu, Zhi-Wei3, 4;  Huang, Chun-Ting3, 4;  Ye, Li-Xin6;  Du, Zuo3, 4;  Yu, Yang2;  Fang, Zhong-Ze7;  Sun, Hong-Zhi1
关键词: Praeruptorin A ;  Praeruptorin B ;  UDP-glucuronosyltransferases (UGTs) ;  drug-drug interaction (DDI)
刊名: PHYTOTHERAPY RESEARCH
发表日期: 2016-11-01
DOI: 10.1002/ptr.5697
卷: 30, 期:11, 页:1872-1878
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
英文摘要: Praeruptorin A (PA) and B (PB) are two important compounds isolated from Bai-hua Qian-hu and have been reported to exert multiple biochemical and pharmacological activities. The present study aims to determine the inhibition of PA and PB on the activity of important phase II drug-metabolizing enzymes uridine 5'-diphosphoglucuronosyltransferase (UGTs) isoforms. In vitro UGT incubation system was used to determine the inhibition potential of PA and PB on the activity of various UGT isoforms. In silico docking was performed to explain the inhibition difference between PA and PB towards the activity of UGT1A6. Inhibition behaviour was determined, and in vitro-in vivo extrapolation was performed by using the combination of in vitro inhibition kinetic parameter (K-i) and in vivo exposure level of PA. Praeruptorin A (100 mu M) exhibited the strongest inhibition on the activity of UGT1A6 and UGT2B7, with 97.8% and 90.1% activity inhibited by 100 mu M of PA, respectively. In silico docking study indicates the significant contribution of hydrogen bond interaction towards the stronger inhibition of PA than PB towards UGT1A6. Praeruptorin A noncompetitively inhibited the activity of UGT1A6 and competitively inhibited the activity of UGT2B7. The inhibition kinetic parameter (K-i) of PA towards UGT1A6 and UGT2B7 was calculated to be 1.2 and 3.3 mu M, respectively. The [I]/K-i value was calculated to be 15.8 and 5.8 for the inhibition of PA on UGT1A6 and UGT2B7, indicating high inhibition potential of PA towards these two UGT isoforms in vivo. Therefore, closely monitoring the interaction between PA and drugs mainly undergoing UGT1A6 or UGT2B7-catalyzed metabolism is very necessary. Copyright (C) 2016 John Wiley & Sons, Ltd.
关键词[WOS]: FLIGHT MASS-SPECTROMETRY ;  CANCER-CELLS ;  KAPPA-B ;  MULTIDRUG-RESISTANCE ;  HYPERBILIRUBINEMIA ;  GLUCURONIDATION ;  2B7 ;  (+/-)-PRAERUPTORIN ;  PHARMACOKINETICS ;  INSIGHTS
语种: 英语
WOS记录号: WOS:000389204000017
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/150452
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.Jinzhou Med Univ, Affiliated Hosp 1, Jinzhou, Liaoning, Peoples R China
2.Tianjin Med Univ, Key Lab Canc Prevent & Therapy, Dept Thyroid & Neck Tumor, Canc Inst & Hosp,Natl Clin Res Ctr Canc, Huanhuxi Rd,Ti Yuan Bei, Tianjin 300060, Peoples R China
3.Chinese Acad Sci, Dalian Inst Chem Phys, Joint Ctr Translat Med, Dalian, Peoples R China
4.Liaoning Med Univ, Affiliated Hosp 1, Dalian, Peoples R China
5.Tianjin Union Med Ctr, 190 Jieyuan Rd, Tianjin 300121, Peoples R China
6.464th Hosp PLA, Dept Radiol, 600 Hongqi South Rd, Tianjin 300381, Peoples R China
7.Tianjin Med Univ, Sch Publ Hlth, Dept Toxicol, 22 Qixiangtai Rd, Tianjin 300070, Peoples R China

Recommended Citation:
Liu, Xin,Chen, Da-Wei,Wu, Xue,et al. The Inhibition of UDP-Glucuronosyltransferase (UGT) Isoforms by Praeruptorin A and B[J]. PHYTOTHERAPY RESEARCH,2016,30(11):1872-1878.
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