Blood–brain barrier transport and neuroprotective potential of blackberry-digested polyphenols: an in vitro study

Abstract
Purpose

Epidemiological and intervention studies have attempted to link the health effects of a diet rich in fruits and vegetables with the consumption of polyphenols and their impact in neurodegenerative diseases. Studies have shown that polyphenols can cross the intestinal barrier and reach concentrations in the bloodstream able to exert effects in vivo. However, the effective uptake of polyphenols into the brain is still regarded with some reservations. Here we describe a combination of approaches to examine the putative transport of blackberry-digested polyphenols (BDP) across the blood–brain barrier (BBB) and ultimate evaluation of their neuroprotective effects.

流行病学和干预研究试图将富含水果和蔬菜的饮食对健康的影响与多酚的消费及其对神经退行性疾病的影响联系起来。研究表明，多酚可以穿过肠道屏障，在血液中达到浓度，从而在体内发挥作用。然而，多酚对大脑的有效吸收仍有一些保留。在这里，我们描述了一种检测黑莓消化多酚(BDP)穿越血脑屏障(BBB)假定运输和最终评估其神经保护作用的方法组合。

Methods

BDP was obtained by in vitro digestion of blackberry extract and BDP major aglycones (hBDP) were obtained by enzymatic hydrolysis. Chemical characterization and BBB transport of extracts were evaluated by LC–MSn. BBB transport and cytoprotection of both extracts was assessed in HBMEC monolayers. Neuroprotective potential of BDP was assessed in NT2-derived 3D co-cultures of neurons and astrocytes and in primary mouse cerebellar granule cells. BDP-modulated genes were evaluated by microarray analysis.

通过对黑莓提取物的体外消化得到BDP，通过酶解得到BDP主要苷元(hBDP)。采用LC-MSn对提取物的化学性质和血脑屏障转运进行了评价。在HBMEC单分子层中评估两种提取物的血脑屏障运输和细胞保护作用。在nt2来源的神经元和星形胶质细胞的3D共培养和原代小鼠小脑颗粒细胞中评估了BDP的神经保护潜力。通过微阵列分析评估bdp调控基因。

Results

Components from BDP and hBDP were shown to be transported across the BBB. Physiologically relevant concentrations of both extracts were cytoprotective at endothelial level and BDP was neuroprotective in primary neurons and in an advanced 3D cell model. The major canonical pathways involved in the neuroprotective effect of BDP were unveiled, including mTOR signaling and the unfolded protein response pathway. Genes such as ASNS and ATF5 emerged as novel BDP-modulated targets.

BDP和hBDP的成分被证明是通过血脑屏障运输的。在内皮水平上，两种提取物的生理相关浓度具有细胞保护作用，而BDP在原代神经元和先进的3D细胞模型中具有神经保护作用。揭示了参与BDP神经保护作用的主要典型通路，包括mTOR信号通路和未展开的蛋白反应通路。ASNS和ATF5等基因成为bdp调控的新靶点。

Conclusions

BBB transport of BDP and hBDP components reinforces the health benefits of a diet rich in polyphenols in neurodegenerative disorders. Our results suggest some novel pathways and genes that may be involved in the neuroprotective mechanism of the BDP polyphenol components.

BDP和hBDP成分的血脑屏障运输加强了富含多酚的饮食对神经退行性疾病的健康益处。我们的研究结果表明，BDP多酚组分的神经保护机制可能涉及一些新的途径和基因。

 

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http://med.wanfangdata.com.cn/Paper/Detail/PeriodicalPaper_PM29151137