Pharmacokinetics of mangiferin and its metabolite-Norathyriol, Part 1: Systemic evaluation of hepatic first-pass effect in vitro and in vivo

doi:10.1002/biof.1291

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 上海中药现代化研究中心

	Pharmacokinetics of mangiferin and its metabolite-Norathyriol, Part 1: Systemic evaluation of hepatic first-pass effect in vitro and in vivo
	Tian, Xiaoting 1; Gao, Yu 1; Xu, Zhou 3; Lian, Shan 2; Ma, Yuanjie 2; Guo, Xiaozhen 1; Hu, Pei 1; Li, Zhixiong1 ; Huang, Chenggang1
刊名	BIOFACTORS
	2016-09
卷号	42 期号:5 页码:533-544
关键词	mangiferin norathyriol pharmacokinetics metabolism liver
ISSN号	0951-6433
DOI	10.1002/biof.1291
文献子类	Article
英文摘要	Mangiferin (MGF), a glucoside of xanthone existing in phytomedicines and food, is increasingly attracting attention on diabetes treatment, while the underlying mechanism leading to its low oral bioavailability is unclear. Norathyriol (NTR), an active metabolite with hypoglycemic activity and its exposure after MGF dosing remains unclear. Hence, a rapid and sensitive LCMS/MS method was established and validated to determine MGF and NTR and applied in the PK study in rats. Correspondingly, the in vitro experiments on temperature-dependent uptake, and MGF metabolism in hepatocyte and enterobacteria samples were performed. Results revealed that hepatic first-pass effect slightly contributed to the poor bioavailability of MGF, based on the MGF exposure in portal vein plasma was nearly similar to that in systemic plasma, and the MGF accumulation in the liver was limited, so was that of NTR. Correspondingly, the in vitro study revealed the MGF uptake was mainly dependent on poor passive transport, possibly leading to its limited hepatic metabolism and accumulation. Moreover, the NTR exposure remained considerably low (C-max<3 ng/mL, AUC(NTR)/AUC(MGF)<3%) in plasma after single MGF dosing, corresponding to its tiny proportion (0.1%) of MGF in MGF-incubated enterobacteria samples. However, given the low generation and elimination rates of NTR, NTR might accumulate in plasma and exert effects after repeated MGF dosing, although requires further study. This work is the first systemic study on PK profiles of MGF and NTR in vitro and in vivo, which is important for the interpretation on the poor bioavailability and pharmacodynamics of MGF. (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	DRUG-DRUG INTERACTIONS ; INDUCED DIABETIC-RATS ; ROSUVASTATIN ; INHIBITION ; EXPRESSION ; XANTHONE ; ACID ; HYPERGLYCEMIA ; TRANSPORTERS ; DISPOSITION
WOS研究方向	Biochemistry & Molecular Biology ; Endocrinology & Metabolism
语种	英语
出版者	WILEY-BLACKWELL
WOS记录号	WOS:000392733000007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275902]
专题	上海中药现代化研究中心
通讯作者	Li, Zhixiong; 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,Gao, Yu,Xu, Zhou,et al. Pharmacokinetics of mangiferin and its metabolite-Norathyriol, Part 1: Systemic evaluation of hepatic first-pass effect in vitro and in vivo[J]. BIOFACTORS,2016,42(5):533-544.
APA	Tian, Xiaoting.,Gao, Yu.,Xu, Zhou.,Lian, Shan.,Ma, Yuanjie.,...&Huang, Chenggang.(2016).Pharmacokinetics of mangiferin and its metabolite-Norathyriol, Part 1: Systemic evaluation of hepatic first-pass effect in vitro and in vivo.BIOFACTORS,42(5),533-544.
MLA	Tian, Xiaoting,et al."Pharmacokinetics of mangiferin and its metabolite-Norathyriol, Part 1: Systemic evaluation of hepatic first-pass effect in vitro and in vivo".BIOFACTORS 42.5(2016):533-544.