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Can Natural Products Exert Neuroprotection without Crossing the Blood–Brain Barrier?

The scope of evidence on the neuroprotective impact of natural products has been greatly extended in recent years. However, a key question that remains to be answered is whether natural products act directly on targets located in the central nervous system (CNS), or whether they act indirectly throu...

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Autores principales: Leclerc, Manon, Dudonné, Stéphanie, Calon, Frédéric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037419/
https://www.ncbi.nlm.nih.gov/pubmed/33805947
http://dx.doi.org/10.3390/ijms22073356
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author Leclerc, Manon
Dudonné, Stéphanie
Calon, Frédéric
author_facet Leclerc, Manon
Dudonné, Stéphanie
Calon, Frédéric
author_sort Leclerc, Manon
collection PubMed
description The scope of evidence on the neuroprotective impact of natural products has been greatly extended in recent years. However, a key question that remains to be answered is whether natural products act directly on targets located in the central nervous system (CNS), or whether they act indirectly through other mechanisms in the periphery. While molecules utilized for brain diseases are typically bestowed with a capacity to cross the blood–brain barrier, it has been recently uncovered that peripheral metabolism impacts brain functions, including cognition. The gut–microbiota–brain axis is receiving increasing attention as another indirect pathway for orally administered compounds to act on the CNS. In this review, we will briefly explore these possibilities focusing on two classes of natural products: omega-3 polyunsaturated fatty acids (n-3 PUFAs) from marine sources and polyphenols from plants. The former will be used as an example of a natural product with relatively high brain bioavailability but with tightly regulated transport and metabolism, and the latter as an example of natural compounds with low brain bioavailability, yet with a growing amount of preclinical and clinical evidence of efficacy. In conclusion, it is proposed that bioavailability data should be sought early in the development of natural products to help identifying relevant mechanisms and potential impact on prevalent CNS disorders, such as Alzheimer’s disease.
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spelling pubmed-80374192021-04-12 Can Natural Products Exert Neuroprotection without Crossing the Blood–Brain Barrier? Leclerc, Manon Dudonné, Stéphanie Calon, Frédéric Int J Mol Sci Review The scope of evidence on the neuroprotective impact of natural products has been greatly extended in recent years. However, a key question that remains to be answered is whether natural products act directly on targets located in the central nervous system (CNS), or whether they act indirectly through other mechanisms in the periphery. While molecules utilized for brain diseases are typically bestowed with a capacity to cross the blood–brain barrier, it has been recently uncovered that peripheral metabolism impacts brain functions, including cognition. The gut–microbiota–brain axis is receiving increasing attention as another indirect pathway for orally administered compounds to act on the CNS. In this review, we will briefly explore these possibilities focusing on two classes of natural products: omega-3 polyunsaturated fatty acids (n-3 PUFAs) from marine sources and polyphenols from plants. The former will be used as an example of a natural product with relatively high brain bioavailability but with tightly regulated transport and metabolism, and the latter as an example of natural compounds with low brain bioavailability, yet with a growing amount of preclinical and clinical evidence of efficacy. In conclusion, it is proposed that bioavailability data should be sought early in the development of natural products to help identifying relevant mechanisms and potential impact on prevalent CNS disorders, such as Alzheimer’s disease. MDPI 2021-03-25 /pmc/articles/PMC8037419/ /pubmed/33805947 http://dx.doi.org/10.3390/ijms22073356 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Review
Leclerc, Manon
Dudonné, Stéphanie
Calon, Frédéric
Can Natural Products Exert Neuroprotection without Crossing the Blood–Brain Barrier?
title Can Natural Products Exert Neuroprotection without Crossing the Blood–Brain Barrier?
title_full Can Natural Products Exert Neuroprotection without Crossing the Blood–Brain Barrier?
title_fullStr Can Natural Products Exert Neuroprotection without Crossing the Blood–Brain Barrier?
title_full_unstemmed Can Natural Products Exert Neuroprotection without Crossing the Blood–Brain Barrier?
title_short Can Natural Products Exert Neuroprotection without Crossing the Blood–Brain Barrier?
title_sort can natural products exert neuroprotection without crossing the blood–brain barrier?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037419/
https://www.ncbi.nlm.nih.gov/pubmed/33805947
http://dx.doi.org/10.3390/ijms22073356
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