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Mol Nutr Food Res. 2015 Jun;59(6):1025-40. doi: 10.1002/mnfr.201400544. Epub 2015 Apr 27.

Role of intestinal microbiota in the generation of polyphenol-derived phenolic acid mediated attenuation of Alzheimer's disease β-amyloid oligomerization.

Author information

1
Center of Nutrition and Food Sciences, ARC center of Excellence in Plant Cell Walls, The University of Queensland, Brisbane, Queensland, Australia.
2
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NJ, USA.
3
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NJ, USA.
4
Department of Neurology and Neurobiology and Aging, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
5
Department of Nutrition Science, Purdue University, West Lafayette, IN, USA.
6
Bindley Bioscience Center, Purdue University, West Lafayette, IN, USA.
7
School of Agriculture and Food Sciences, The University of Queensland, Brisbane, Queensland, Australia.
8
Department of Food Science, Purdue University, West Lafayette, IN, USA.
9
Geriatric Research and Clinical Center, James J. Peter Veterans Affairs Medical Center, Bronx, NY, USA.

Erratum in

Abstract

SCOPE:

Grape seed polyphenol extract (GSPE) is receiving increasing attention for its potential preventative and therapeutic roles in Alzheimer's disease (AD) and other age-related neurodegenerative disorders. The intestinal microbiota is known to actively convert many dietary polyphenols, including GSPE, to phenolic acids. There is limited information on the bioavailability and bioactivity of GSPE-derived phenolic acid in the brain.

METHODS AND RESULTS:

We orally administered GSPE to rats and investigated the bioavailability of 12 phenolic acids known to be generated by microbiota metabolism of anthocyanidins. GSPE treatment significantly increased the content of two of the phenolic acids in the brain: 3-hydroxybenzoic acid and 3-(3´-hydroxyphenyl)propionic acid, resulting in the brain accumulations of the two phenolic acids at micromolar concentrations. We also provided evidence that 3-hydroxybenzoic acid and 3-(3´-hydroxyphenyl)propionic acid potently interfere with the assembly of β-amyloid peptides into neurotoxic β-amyloid aggregates that play key roles in AD pathogenesis.

CONCLUSION:

Our observation suggests important contribution of the intestinal microbiota to the protective activities of GSPE (as well as other polyphenol preparations) in AD. Outcomes from our studies support future preclinical and clinical investigations exploring the potential contributions of the intestinal microbiota in protecting against the onset/progression of AD and other neurodegenerative conditions.

KEYWORDS:

Bioavailability; Grape seed polyphenol extract; Phenolic metabolites; Proanthocyanidins; β-Amyloid

PMID:
25689033
PMCID:
PMC4498582
DOI:
10.1002/mnfr.201400544
[Indexed for MEDLINE]
Free PMC Article

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