Transport characteristics of isorhamnetin across intestinal Caco-2 cell monolayers and the effects of transporters on it

被引：39
作者：
Duan, Jingze [1 ,2 ]
Xie, Yan [2 ]
Luo, Huilin [2 ,3 ]
Li, Guowen [4 ]
Wu, Tao [1 ]
Zhang, Tong [3 ]
机构：
[1] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, Shanghai 201203, Peoples R China
[2] Shanghai Univ Tradit Chinese Med, Res Ctr Hlth & Nutr, Shanghai 201203, Peoples R China
[3] Shanghai Univ Tradit Chinese Med, Expt Ctr Teaching & Learning, Shanghai 201203, Peoples R China
[4] Shanghai TCM Integrated Hosp, Dept Pharm, Shanghai 200082, Peoples R China
来源：
FOOD AND CHEMICAL TOXICOLOGY | 2014年 / 66卷
基金：
美国国家科学基金会;
关键词：
Absorption mechanism; Transport; Isorhamnetin; Caco-2; cell; Transporters; RESISTANCE-ASSOCIATED PROTEIN-2; IN-VITRO; FLAVONOID QUERCETIN; P-GLYCOPROTEIN; DRUG-DELIVERY; LINE CACO-2; ABSORPTION; PERMEABILITY; EFFLUX; METABOLISM;
D O I：
10.1016/j.fct.2014.02.003
中图分类号：
TS2 [食品工业];
学科分类号：
0832 ;
摘要：
Flavonoid isorhamnetin occurs in various plants and herbs, and demonstrates various biological effects in humans. This work will clarify the isorhamnetin absorption mechanism using the Caco-2 monolayer cell model. The isorhamnetin transport characteristics at different concentrations, pHs, temperatures, tight junctions and potential transporters were systemically investigated. lsorhamnetin was poorly absorbed by both passive diffusion and active transport mechanisms. Both trans- and paracellular pathways were involved during isorhamnetin transport. Active transport under an ATP-dependent transport mechanism was mediated by the organic anion transporting peptide (OATP); isorhamnetin's permeability from the apical to the basolateral side significantly decreased after estrone-3-sulfate was added (p < 0.01). Efflux transporters, P-glycoproteins (P-gp), breast cancer resistance proteins (BCRP) and multidrug resistance proteins (MRPs) participated in the isorhamnetin transport process. Among them, the MRPs (especially MRP2) were the main efflux transporters for isorhamnetin; transport from the apical to the basolateral side increased 10.8-fold after adding an MRP inhibitor (MK571). This study details isorhamnetin's cellular transport and elaborates isorhamnetin's absorption mechanisms to provide a foundation for further studies. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码：313 / 320
页数：8
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