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Eur J Nutr. 2019 Feb;58(1):113-130. doi: 10.1007/s00394-017-1576-y. Epub 2017 Nov 18.

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

Author information

1
Instituto de Tecnologia Quı́mica e Biológica-António Xavier, Universidade Nova de Lisboa, Av. da República, EAN, 2780-157, Oeiras, Portugal.
2
iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901, Oeiras, Portugal.
3
Wageningen Food & Biobased Research, Wageningen University and Research, Wageningen, The Netherlands.
4
Instituto Gulbenkian de Ciência, 2780-156, Oeiras, Portugal.
5
The James Hutton Institute, Invergowrie, Dundee, DD2 5DA, Scotland, UK.
6
School of Engineering and Physical Sciences, Heriot Watt University, Edinburgh, EH14 4AS, Scotland, UK.
7
NIBIO, Norwegian Institute of Bioeconomy Research, Pb 115, 1431, Ås, Norway.
8
Medical Department, Grupo Tecnimede, 2710-089, Sintra, Portugal.
9
Division of Infectious Diseases, Johns Hopkins University School of Medicine, 600 North Wolfe Street Park 256, Baltimore, MD, 21287, USA.
10
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal.
11
Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal.
12
Instituto de Tecnologia Quı́mica e Biológica-António Xavier, Universidade Nova de Lisboa, Av. da República, EAN, 2780-157, Oeiras, Portugal. csantos@itqb.unl.pt.
13
iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901, Oeiras, Portugal. csantos@itqb.unl.pt.

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.

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.

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.

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.

KEYWORDS:

Blackberry; Brain endothelial cells; In vitro digestion; Microarrays; Neuronal cells

PMID:
29151137
DOI:
10.1007/s00394-017-1576-y
[Indexed for MEDLINE]

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