Bioavailability of gallic acid and catechins from grape seed polyphenol extract is improved by repeated dosing in rats: implications for treatment in Alzheimer's disease.
Bioavailability of gallic acid and catechins from grape seed polyphenol extract is improved by repeated dosing in rats: implications for treatment in Alzheimer's disease.
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DOI：
10.3233/jad-2009-1135
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Pasinetti GM
中科院分区：
文献类型：
--
作者：
Ferruzzi MG;Lobo JK;Janle EM;Cooper B;Simon JE;Wu QL;Welch C;Ho L;Weaver C;Pasinetti GM
本研究探索了葡萄籽多酚提取物(GSPE)的生物利用度和脑沉积，此前已发现GSPE可减轻阿尔茨海默病(AD)小鼠模型的认知退化。以50、100和150 mg/kgbw的GSPE灌胃给药，测定其主要酚类成分的血浆药代动力学。用LC-MS分析了急性灌胃GSPE大鼠血浆中没食子酸(GA)、儿茶素(C)、表儿茶素(EC)的含量。此外，4-甲基没食子酸(4-omega)、3‘-甲基儿茶素(3’-Omec)和3‘-甲基苦皮儿茶素(3’-OMeEC)是GSPE酚类成分的循环代谢产物。各GSPE成分及其代谢物的Cmax呈剂量依赖性增加(随着GSPE口服剂量的增加)。与只接受一次急性GSPE剂量的动物相比，每天重复暴露于GSPE可显著增加GA、C和EC的生物利用度(定义为血浆AUC0-8h)198、253和282%。单次给药组大鼠脑组织中未检测到EC和C，连续给药10天的脑组织中EC和C的含量分别为290.7±45.9pg/g和576.7±227.7 pg/g。这项研究表明，重复给予GSPE会影响大脑中GA、C和EC的沉积。
The present study explored the bioavailability and brain deposition of a Grape Seed Polyphenolic Extract (GSPE) previously found to attenuate cognitive deterioration in a mouse model of Alzheimer’s disease (AD). Plasma pharmacokinetic response of major GSPE phenolic components was measured following intragastric gavage of 50, 100 and 150 mg GSPE per kg BW. LC-MS analysis identified gallic acid (GA), catechin (C), epicatechin (EC) in plasma of rats gavaged acutely with GSPE. Additionally, 4-methylgallic acid (4-OMeGA), 3′-methytlcatechin (3′-OMeC) and 3′-methylepicatechin (3′-OMeEC) were identified as circulating metabolites of GSPE phenolic constituents. Cmax for individual GSPE constituents and their metabolites increased in a dose-dependent fashion (with increasing GSPE oral dose). Repeated daily exposure to GSPE was found to significantly increase bioavailability (defined as plasma AUC0-8h) of GA, C and EC by 198, 253 and 282% relative to animals receiving only a single acute GSPE dose. EC and C were not detectable in brain tissues of rats receiving a single GSPE dose but reached levels of 290.7±45.9 and 576.7±227.7 pg/g in brain tissues from rats administered GSPE for 10 days. This study suggests that brain deposition of GA, C and EC is affected by repeated dosing of GSPE.