{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:55:36Z","timestamp":1790430936569,"version":"4.1.0"},"reference-count":235,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003151","name":"Fonds de recherche du Qu\u00e9bec \u2013 Nature et technologies","doi-asserted-by":"publisher","award":["2021-PR-281704"],"award-info":[{"award-number":["2021-PR-281704"]}],"id":[{"id":"10.13039\/501100003151","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000156","name":"Fonds de Recherche du Qu\u00e9bec - Sant\u00e9","doi-asserted-by":"publisher","award":["253895"],"award-info":[{"award-number":["253895"]}],"id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013brain barrier, it has been recently uncovered that peripheral metabolism impacts brain functions, including cognition. The gut\u2013microbiota\u2013brain 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\u2019s disease.<\/jats:p>","DOI":"10.3390\/ijms22073356","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T14:51:12Z","timestamp":1616683872000},"page":"3356","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Can Natural Products Exert Neuroprotection without Crossing the Blood\u2013Brain Barrier?"],"prefix":"10.3390","volume":"22","author":[{"given":"Manon","family":"Leclerc","sequence":"first","affiliation":[{"name":"Facult\u00e9 de Pharmacie, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"},{"name":"Axe Neurosciences, Centre de Recherche du CHU de Qu\u00e9bec\u2013Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 4G2, Canada"},{"name":"Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Qu\u00e9bec, QC G1V 0A6, Canada"},{"name":"OptiNutriBrain-Laboratoire International Associ\u00e9 (NutriNeuro France-INAF Canada), Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6581-4070","authenticated-orcid":false,"given":"St\u00e9phanie","family":"Dudonn\u00e9","sequence":"additional","affiliation":[{"name":"Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Qu\u00e9bec, QC G1V 0A6, Canada"},{"name":"OptiNutriBrain-Laboratoire International Associ\u00e9 (NutriNeuro France-INAF Canada), Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4203-0887","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Calon","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de Pharmacie, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"},{"name":"Axe Neurosciences, Centre de Recherche du CHU de Qu\u00e9bec\u2013Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 4G2, Canada"},{"name":"Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Qu\u00e9bec, QC G1V 0A6, Canada"},{"name":"OptiNutriBrain-Laboratoire International Associ\u00e9 (NutriNeuro France-INAF Canada), Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.tips.2020.03.004","article-title":"Improving the Accuracy of Predicted Human Pharmacokinetics: Lessons Learned from the AstraZeneca Drug Pipeline Over Two Decades","volume":"41","author":"Davies","year":"2020","journal-title":"Trends Pharmacol. 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