期刊
TOXICOLOGY IN VITRO
卷 28, 期 3, 页码 388-396出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2013.12.002
关键词
Flavonoids; Blood-brain barrier cell; Caco-2 cell; Transport; Cytotoxicity
类别
资金
- National Foundation of Natural Sciences of China [30472057, 81173121]
- Beijing Natural Science Foundation Program [7052007, KZ201110025024]
- Funding Project for Academic Human Resources Development in Institutions of High Learning under the Jurisdicrion of Beijing Municipality [PHR201007111]
This in vitro study aims to evaluate and compare transmembrane transport of eight cardio-cerebrovascular protection flavonoids including puerarin, rutin, hesperidin, quercetin, genistein, kaempferol, apigenin and isoliquiritigenin via the rat blood-brain barrier cell and Caco-2 cell monolayer models, based on the data of cytotoxicity and lipophilicity. The cytotoxicity of the flavonoids to rat brain microvessel endothelial cell was determined by the MU assay. The apparent permeability coefficients (P-app) of the flavonoids were calculated from the unilateral transport assays in Transwell system with simultaneous determination using a high performance liquid chromatography. The results showed that the cytotoxicity and oilwater partition coefficient of the flavonoids modified by the number and position of the glycoside and hydroxyl group were the key determinant for the transmembrane transport. The P-app values of the flavonoids reduced adversely when the numbers of glycoside and hydroxyl groups of the flavonoids increased accordingly. The tested flavonoids exhibited time-dependent P-app values in these models. The efflux mechanism related with P-glycoprotein also existed with the polar flavonoids; verapamil could enhance the permeation of rutin and quercetin via inhibition of P-glycoprotein. We propose that genistein and isoliquiritigenin with the permeation priority in vitro Caco-2 and BBB cell model could be better as the drug candidates for cardio-cerebral vascular protection. These findings provided important information for establishing the transport relationship for the flavonoid compounds and evaluating the potential oral bioavailability and brain distribution of the flavonoids. (C) 2013 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据