Pharmacokinetics of mangiferin and its metabolite-Norathyriol, Part 2: Influence of UGT, CYP450, P-gp, and enterobacteria and the potential interaction in Rhizoma Anemarrhenae decoction with timosaponin B2 as the major contributor

doi:10.1002/biof.1290

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	Pharmacokinetics of mangiferin and its metabolite-Norathyriol, Part 2: Influence of UGT, CYP450, P-gp, and enterobacteria and the potential interaction in Rhizoma Anemarrhenae decoction with timosaponin B2 as the major contributor
	Tian, Xiaoting 1; Xu, Zhou 3; Li, Zhixiong1 ; Ma, Yuanjie 2; Lian, Shan 2; Guo, Xiaozhen 1; Hu, Pei 1; Gao, Yu 1; Huang, Chenggang1
刊名	BIOFACTORS
	2016-09
卷号	42 期号:5 页码:545-555
关键词	mangiferin norathyriol pharmacokinetics drug-drug interaction timosaponin B2 Rhizoma Anemarrhenae
ISSN号	0951-6433
DOI	10.1002/biof.1290
文献子类	Article
英文摘要	The poor bioavailability of mangiferin (MGF) is a major obstacle on its further development. Aimed to illustrate the underlying mechanism and improve its poor exposure, the compared PK profiles of MGF and norathyriol (NTR) after different MGF preparation were performed: pure MGF, the Rhizoma Anemarrhenae (Zhi-mu) decoction, MGF, and timosaponin B2 (TB-2) combination. Furthermore, the potential contributing factors, including uridine diphosphoglucuronosyltransferase (UGT), cytochrome P450 (CYP450), P-gp, and enterobacterial were investigated by comparing the PK profiles with and without the corresponding inhibitors or in different rat models. After taking MGF, CYP450 and UGT inhibition could decrease MGF and NTR exposure; P-gp inhibition slightly enhanced (48%) MGF exposure, whereas more apparent for the improved NTR exposure (302%); enterobacterial inhibition almost completely stopped the NTR production, but no such effect was observed for MGF. Compared with the limited improvement by the abovementioned inhibition, the MGF and NTR exposure could significantly increase by 11.5- and 5.9-fold in the Zhi-mu decoction compared with the MGF treatment, probably contributed to TB-2 as an absorption enhancer because the MGF and TB-2 combination produced a similar level of improvement on the PK paremeters of MGF and NTR to the herb treatment. Likewise, most of the effects by UGT, CYP450, P-gp, and enterobacteria followed a similar variation tendency between them. Therefore, the poor bioavailability of MGF possibly mainly attributed to its poor membrane permeability, but not transporters or metabolic enzymes, and the compatibility of MGF and TB-2 could probably expand the prospective application of MGF by improving its bioavailability. (C) 2016 BioFactors.
资助项目	State Key Program of National Natural Science Foundation of China[81030065] ; National Science and Technology Major Project[2009ZX09102121] ; National Science and Technology Major Project[2013ZX09102027] ; China Postdoctoral Science Foundation[159994]
WOS关键词	INDUCED DIABETIC-RATS ; IN-VIVO ; ASPHODELOIDES ; BERBERINE ; EXTRACT ; ABSORPTION ; CYTOCHROME-P450 ; BIOAVAILABILITY ; PERMEABILITY ; INHIBITION
WOS研究方向	Biochemistry & Molecular Biology ; Endocrinology & Metabolism
语种	英语
出版者	WILEY-BLACKWELL
WOS记录号	WOS:000392733000008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275903]
专题	上海中药现代化研究中心
通讯作者	Gao, Yu; Huang, Chenggang
作者单位	1.Univ Chinese Acad Sci, Shanghai Inst Mat Med, Modernizat Tradit Chinese Med, Shanghai, Peoples R China; 2.Harbin Univ Commerce, Dept Pharm, Harbin, Peoples R China 3.Shanghai Normal Univ, Coll Life & Environm Sci, Shanghai, Peoples R China;
推荐引用方式 GB/T 7714	Tian, Xiaoting,Xu, Zhou,Li, Zhixiong,et al. Pharmacokinetics of mangiferin and its metabolite-Norathyriol, Part 2: Influence of UGT, CYP450, P-gp, and enterobacteria and the potential interaction in Rhizoma Anemarrhenae decoction with timosaponin B2 as the major contributor[J]. BIOFACTORS,2016,42(5):545-555.
APA	Tian, Xiaoting.,Xu, Zhou.,Li, Zhixiong.,Ma, Yuanjie.,Lian, Shan.,...&Huang, Chenggang.(2016).Pharmacokinetics of mangiferin and its metabolite-Norathyriol, Part 2: Influence of UGT, CYP450, P-gp, and enterobacteria and the potential interaction in Rhizoma Anemarrhenae decoction with timosaponin B2 as the major contributor.BIOFACTORS,42(5),545-555.
MLA	Tian, Xiaoting,et al."Pharmacokinetics of mangiferin and its metabolite-Norathyriol, Part 2: Influence of UGT, CYP450, P-gp, and enterobacteria and the potential interaction in Rhizoma Anemarrhenae decoction with timosaponin B2 as the major contributor".BIOFACTORS 42.5(2016):545-555.