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Review

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

by 1,2,3,4, 3,4 and 1,2,3,4,*
1
Faculté de Pharmacie, Université Laval, Québec, QC G1V 0A6, Canada
2
Axe Neurosciences, Centre de Recherche du CHU de Québec–Université Laval, Québec, QC G1V 4G2, Canada
3
Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Québec, QC G1V 0A6, Canada
4
OptiNutriBrain-Laboratoire International Associé (NutriNeuro France-INAF Canada), Québec, QC G1V 0A6, Canada
*
Author to whom correspondence should be addressed.
Academic Editor: Cristina Angeloni
Int. J. Mol. Sci. 2021, 22(7), 3356; https://doi.org/10.3390/ijms22073356
Received: 25 February 2021 / Revised: 19 March 2021 / Accepted: 20 March 2021 / Published: 25 March 2021
(This article belongs to the Special Issue Natural Products and Neuroprotection 3.0)
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. View Full-Text
Keywords: blood–brain barrier; central nervous system; bioavailability; polyphenols; omega-3 polyunsaturated fatty acids; gut–brain axis blood–brain barrier; central nervous system; bioavailability; polyphenols; omega-3 polyunsaturated fatty acids; gut–brain axis
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MDPI and ACS Style

Leclerc, M.; Dudonné, S.; Calon, F. Can Natural Products Exert Neuroprotection without Crossing the Blood–Brain Barrier? Int. J. Mol. Sci. 2021, 22, 3356. https://doi.org/10.3390/ijms22073356

AMA Style

Leclerc M, Dudonné S, Calon F. Can Natural Products Exert Neuroprotection without Crossing the Blood–Brain Barrier? International Journal of Molecular Sciences. 2021; 22(7):3356. https://doi.org/10.3390/ijms22073356

Chicago/Turabian Style

Leclerc, Manon, Stéphanie Dudonné, and Frédéric Calon. 2021. "Can Natural Products Exert Neuroprotection without Crossing the Blood–Brain Barrier?" International Journal of Molecular Sciences 22, no. 7: 3356. https://doi.org/10.3390/ijms22073356

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