Strong Specific Inhibition of UDP-glucuronosyltransferase 2B7 by Atractylenolide I and III

doi:10.1002/ptr.5496

	Strong Specific Inhibition of UDP-glucuronosyltransferase 2B7 by Atractylenolide I and III
	Cao, Yun-Feng 4; Ran, Rui-Xue 5; Li, Rong-Shan 5; Zhang, Qian 3; Wu, Xue 3,6,7,8; Dong, Pei-Pei 9; Zhang, Yan-Yan 1,6,7; Hu, Cui-Min 2; Wang, Wei-Ming 3
刊名	PHYTOTHERAPY RESEARCH
	2016
卷号	30 期号:1 页码:25-30
关键词	Atractylenolide i Atractylenolide Iii Drug-drug Interaction
ISSN号	0951-418X
DOI	10.1002/ptr.5496
文献子类	Article
英文摘要	Drug-metabolizing enzymes inhibition-based drug-drug interaction remains to be the key limiting factor for the research and development of efficient herbal components to become clinical drugs. The present study aims to determine the inhibition of uridine 5-diphospho-glucuronosyltransferases (UGTs) isoforms by two important efficient herbal ingredients isolated from Atractylodes macrocephala Koidz, atractylenolide I and III. In vitro recombinant UGTs-catalysed glucuronidation of 4-methylumbelliferone was used to determine the inhibition capability and kinetics of atractylenolide I and III towards UGT2B7, and in silico docking method was employed to explain the possible mechanism. Atractylenolide I and III exhibited specific inhibition towards UGT2B7, with negligible influence towards other UGT isoforms. Atractylenolide I exerted stronger inhibition potential than atractylenolide III towards UGT2B7, which is attributed to the different hydrogen bonds and hydrophobic interactions. Inhibition kinetic analysis was performed for the inhibition of atractylenolide I towards UGT2B7. Inhibition kinetic determination showed that atractylenolide I competitively inhibited UGT2B7, and inhibition kinetic parameter (Ki) was calculated to be 6.4M. In combination of the maximum plasma concentration of atractylenolide I after oral administration of 50mg/kg atractylenolide I, the area under the plasma concentration-time curve ration AUC(i)/AUC was calculated to be 1.17, indicating the highly possible drug-drug interaction between atractylenolide I and drugs mainly undergoing UGT2B7-catalysed metabolism. Copyright (c) 2015 John Wiley & Sons, Ltd.
WOS关键词	BILE-ACIDS ; VITRO ; UGT2B7 ; HYPERBILIRUBINEMIA ; GLUCURONIDATION ; ZIDOVUDINE ; VIVO ; UGTS
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	WILEY-BLACKWELL
WOS记录号	WOS:000367919300004
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/171480]
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	Wang, Wei-Ming
作者单位	1.Liaoning Med Univ, Affiliated Hosp 1, Jinzhou 121001, Liaoning, Peoples R China 2.Tianjin Med Univ, Sch Basic Med Sci, Dept Microbiol, Tianjin 300070, Peoples R China 3.Dalian Univ, Affiliated Zhongshan Hosp, Dalian 116001, Liaoning, Peoples R China 4.Shanghai Engineer & Technol Res Ctr Reprod Hlth D, Shanghai Inst Planned Parenthood Res, Key Lab Contracept & Devices Res NPFPC, Shanghai 200032, Peoples R China 5.Tianjin Med Univ, Sch Pharm, Tianjin Key Lab Technol Enabling Dev Clin Therape, Tianjin 300070, Peoples R China 6.Chinese Acad Sci, Joint Ctr Translat Med, Dalian Inst Chem Phys, Dalian 116023, Peoples R China 7.Liaoning Med Univ, Affiliated Hosp 1, Dalian 116023, Peoples R China 8.Chinese Acad Sci, Joint Ctr Translat Med, Dalian Inst Chem Phys, Dalian 116001, Peoples R China 9.Dalian Med Univ, Inst Integrat Med, Dalian 116044, Peoples R China
推荐引用方式 GB/T 7714	Cao, Yun-Feng,Ran, Rui-Xue,Li, Rong-Shan,et al. Strong Specific Inhibition of UDP-glucuronosyltransferase 2B7 by Atractylenolide I and III[J]. PHYTOTHERAPY RESEARCH,2016,30(1):25-30.
APA	Cao, Yun-Feng.,Ran, Rui-Xue.,Li, Rong-Shan.,Zhang, Qian.,Wu, Xue.,...&Wang, Wei-Ming.(2016).Strong Specific Inhibition of UDP-glucuronosyltransferase 2B7 by Atractylenolide I and III.PHYTOTHERAPY RESEARCH,30(1),25-30.
MLA	Cao, Yun-Feng,et al."Strong Specific Inhibition of UDP-glucuronosyltransferase 2B7 by Atractylenolide I and III".PHYTOTHERAPY RESEARCH 30.1(2016):25-30.