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Cited by 290Phytochemicals and Antioxidant ActivitiesBarrier Structure and Function StudiesNeuroinflammation and Neurodegeneration Mechanisms

Polyphenols journey through blood-brain barrier towards neuronal protection

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Figueira, I., Garcia, G., Pimpão, R. C., Terrasso, A. P., Costa, I., Almeida, A. F., Tavares, L., Pais, T. F. +11 more·2017·Scientific Reports
DOI 10.1038/s41598-017-11512-6PMC PMC5597593
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Abstract

Age-related complications such as neurodegenerative disorders are increasing and remain cureless. The possibility of altering the progression or the development of these multifactorial diseases through diet is an emerging and attractive approach with increasing experimental support. We examined the potential of known bioavailable phenolic sulfates, arising from colonic metabolism of berries, to influence hallmarks of neurodegenerative processes. In silico predictions and in vitro transport studies across blood-brain barrier (BBB) endothelial cells, at circulating concentrations, provided evidence for differential transport, likely related to chemical structure. Moreover, endothelial metabolism of these phenolic sulfates produced a plethora of novel chemical entities with further potential bioactivies. Pre-conditioning with phenolic sulfates improved cellular responses to oxidative, excitotoxicity and inflammatory injuries and this attenuation of neuroinflammation was achieved via modulation of NF-κB pathway. Our results support the hypothesis that these small molecules, derived from dietary (poly)phenols may cross the BBB, reach brain cells, modulate microglia-mediated inflammation and exert neuroprotective effects, with potential for alleviation of neurodegenerative diseases.

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  • Recent studies with certain polyphenol metabolites, namely gallic acid derivatives, demonstrated that these metabolites pass across BBB endothelium and provide neuroprotective effects through modulation of the NF-κB pathway.

    “Recent studies with certain polyphenol metabolites, namely gallic acid derivatives, demonstrated that these metabolites pass across BBB endothelium and provide neuroprotective effects through modulation of the NF-κB pathway [55].”

    From Polyphenol Microbial Metabolites Exhibit Gut and Blood–Brain Barrier Permeability and Protect Murine Microglia against LPS-Induced Inflammation (2019) · cites this paper as [55]

    The Results section on BBB transport reports that gallic acid derivatives crossed the in vitro BBB endothelium, and the Results section on neuronal protection reports protective effects from the metabolites studied. But the NF-κB experiments identify pyrogallol-O-sulfate (Pyr-sulf), not a gallic acid derivative, as the metabolite that altered NF-κB signaling. The claim incorrectly joins that mechanism to gallic acid derivatives. (LLM, conf=0.87)

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Authors
Figueira, I., Garcia, G., Pimpão, R. C., Terrasso, A. P., Costa, I., Almeida, A. F., Tavares, L., Pais, T. F., Pinto, P., Ventura, M. R., Filipe, A., McDougall, G. J., Stewart, D., Kim, K. S., Palmela, I., Brites, D., Brito, M. A., Brito, C., & Santos, C. N.
Affiliations
  • Instituto de Biologia Experimental e Tecnológica (PT)
  • Instituto Gulbenkian de Ciência (PT)
  • Universidade Politécnica de Santarém (PT)
  • Instituto de Tecnologia Química e Biológica António Xavier (PT)
  • Grupo Tecnimede (Portugal) (PT)
  • James Hutton Institute (GB)
  • Johns Hopkins University (US)
  • University of Lisbon (PT)
Corresponding author
Santos, C. N.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2017-09-13
Volume
7
Issue
1
Pages
11456-11456
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-017-11512-6
PMC
PMC5597593
OpenAlex
W2751480807
Cited by
290
References
5
Citations by year
2026: 31 · 2025: 35 · 2024: 40 · 2023: 33 · 2022: 43 · 2021: 38 · 2020: 35 · 2019: 20 · 2018: 13 · 2017: 2
FWCI
12.93
Type
journal article
Language
en
Update notices
correction (2021-08-18)
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • BIBSYS Brage (BIBSYS (Norway)) (acceptedVersion, cc-by)
  • NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by)
Funders
  • Scottish Government
  • Universidade de Lisboa (UID/DTP/04138/2013)
  • Fundação para a Ciência e a Tecnologia (01-0145, 04138, PT2020, UID/DTP/04138/2013, LISBOA‐01‐0145‐FEDER‐007344, IF/01097/2013, SFRH/BD/86584/2012, SFRH/BD/63615/2009, iNOVA4Health, /2009, PD/BD/52473/2014, LISBOA-01-0145-FEDER)
  • European Regional Development Fund (UID/DTP/04138/2013, 01-0145, PT2020, LISBOA-01-0145-FEDER-007344, PD/BD/52473/2014)
  • National Institute of Neurological Disorders and Stroke (R01NS091102)
Topics
  • Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
polyphenols, blood-brain barrier, colonic metabolism, berries, neurodegenerative diseases, neuroprotection, endothelial cells, oxidative stress, excitotoxicity, neuroinflammation, NF-κB signaling, microglia, dietary polyphenols, in silico prediction
MeSH terms
Animals, Biological Availability, Biological Transport, Blood-Brain Barrier, Cell Line, Cerebellum, Chromatography, Liquid, Humans, Neurons, Permeability, Mass Spectrometry, Biomarkers, NF-kappa B, Microglia, Neuroprotective Agents, Protein Transport, Mice, Polyphenols, Human Umbilical Vein Endothelial Cells

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