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通过与α-生育酚共同给药增强黄酮类化合物穿越大鼠血脑屏障的能力。

Enhancement of flavonoid ability to cross the blood-brain barrier of rats by co-administration with α-tocopherol.

作者信息

Ferri Paola, Angelino Donato, Gennari Lorenzo, Benedetti Serena, Ambrogini Patrizia, Del Grande Paolo, Ninfali Paolino

机构信息

Department of Earth, Life and Environmental Sciences, University of Urbino "Carlo Bo", Via Ca' Le Suore 2/4, 61029 Urbino, PU, Italy.

出版信息

Food Funct. 2015 Feb;6(2):394-400. doi: 10.1039/c4fo00817k.

DOI:10.1039/c4fo00817k
PMID:25474041
Abstract

Vitamin E and polyphenols could exhibit a therapeutic role in the treatment of oxidative stress-induced neurodegenerative diseases. Therefore, their ability to cross the blood-brain barrier (BBB) represents an important issue to be explored by different diet combinations. In this study, we have evaluated the ability of α-tocopherol to support epigallocatechin-3-gallate (EGCG), quercetin and rutin to cross the BBB, following oral administration. Eighteen rats were fed a standard diet (C), a diet supplemented with α-tocopherol (A), with a mixture of EGCG, quercetin and rutin (P); or with a mixture of α-tocopherol and the three flavonoids (AP). Flavonoids and their conjugated derivatives were assayed in brain and plasma by HPLC-MS, whereas α-tocopherol was detected by RP-HPLC. The oxidative damage, due to the potential pro-oxidant activity of flavonoids, was evaluated by the presence of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in hippocampal Cornus Ammonis, one of the most vulnerable sites in the brain. Our results indicate that α-tocopherol is able to promote quercetin transport across the BBB. The mixture of rutin and quercetin seems to favour the accumulation of quercetin and/or its conjugated derivatives in the brain. In contrast, α-tocopherol does not affect EGCG transport across the BBB. The densitometric analysis of 8-OHdG immunoreactivity does not reveal any difference of oxidative damage among the experimental groups. Our results suggest that α-tocopherol may promote quercetin transport across the BBB, leading to a significant increase of α-tocopherol and quercetin concentration in the brain.

摘要

维生素E和多酚类物质在治疗氧化应激诱导的神经退行性疾病中可能发挥治疗作用。因此,它们穿越血脑屏障(BBB)的能力是不同饮食组合需要探索的一个重要问题。在本研究中,我们评估了口服给药后α-生育酚辅助表没食子儿茶素-3-没食子酸酯(EGCG)、槲皮素和芦丁穿越血脑屏障的能力。将18只大鼠分为四组,分别喂食标准饮食(C组)、补充α-生育酚的饮食(A组)、补充EGCG、槲皮素和芦丁混合物的饮食(P组);或补充α-生育酚与三种黄酮类化合物混合物的饮食(AP组)。通过高效液相色谱-质谱联用(HPLC-MS)测定大脑和血浆中的黄酮类化合物及其共轭衍生物,而通过反相高效液相色谱(RP-HPLC)检测α-生育酚。由于黄酮类化合物潜在的促氧化活性导致的氧化损伤,通过海马区角回中8-羟基-2'-脱氧鸟苷(8-OHdG)的存在来评估,海马区是大脑中最脆弱的部位之一。我们的结果表明,α-生育酚能够促进槲皮素穿越血脑屏障。芦丁和槲皮素的混合物似乎有利于槲皮素和/或其共轭衍生物在大脑中的积累。相比之下,α-生育酚不影响EGCG穿越血脑屏障。对8-OHdG免疫反应性的光密度分析未显示各实验组之间氧化损伤有任何差异。我们的结果表明,α-生育酚可能促进槲皮素穿越血脑屏障,导致大脑中α-生育酚和槲皮素浓度显著增加。

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