Plant Extracts and ω-3 Improve Short-Term Memory and Modulate the Microbiota-Gut-Brain Axis in D-galactose Model Mice.
The Journal of Nutrition. 2024-12-01; 154(12): 3704-3717
DOI: 10.1016/j.tjnut.2024.09.015

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Martin M(1), Boulaire M(2), Lucas C(3), Peltier A(3), Pourtau L(4), Gaudout
D(4), Layé S(2), Pallet V(2), Joffre C(2), Dinel AL(5).
Author information:
(1)Université Bordeaux, INRAE, Bordeaux INP, Nutrineuro, Bordeaux, France;
Activ’Inside, 12 route de Beroy, ZA du Grand Cazeau, Beychac-et-Caillau.
(2)Université Bordeaux, INRAE, Bordeaux INP, Nutrineuro, Bordeaux, France.
(3)Université Bordeaux, INRAE, Bordeaux INP, Nutrineuro, Bordeaux, France;
NutriBrain Research and Technology Transfer, NutriNeuro, Bordeaux, France.
(4)Activ’Inside, 12 route de Beroy, ZA du Grand Cazeau, Beychac-et-Caillau.
(5)Université Bordeaux, INRAE, Bordeaux INP, Nutrineuro, Bordeaux, France;
NutriBrain Research and Technology Transfer, NutriNeuro, Bordeaux, France.
Electronic address: .
BACKGROUND: Aging, characterized by a slow and progressive alteration of
cognitive functions, is associated with gut microbiota dysbiosis, low-grade
chronic inflammation, as well as increased oxidative stress and neurofunctional
alterations. Some nutrients, such as polyphenols, carotenoids, and omega (ω)-3
(n-3), are good candidates to prevent age-related cognitive decline, because of
their immunomodulatory, antioxidant, and neuroprotective properties.
OBJECTIVES: The objective of this study was to demonstrate the preventive effect
of a combination of plant extracts (PE) containing Memophenol™ (grapes and
blueberries polyphenols) and a patented saffron extract (saffron carotenoids and
safranal) and ω-3 on cognitive function in a mouse model of accelerated aging
and to understand the biological mechanisms involved.
METHODS: We used an accelerated-aging model by injecting 3-mo-old male C57Bl6/J
mice with D-galactose for 8 wk, during which they were fed with a balanced
control diet and supplemented or not with PE and/or ω-3 (n = 15-16/group).
Short-term memory was evaluated by Y-maze test, following analyses of
hippocampal and intestinal RNA expressions, brain fatty acid and oxylipin
amounts, and gut microbiota composition (16S rRNA gene sequencing). Statistical
analyses were performed (t test, analysis of variance, and Pearson correlation).
RESULTS: Our results showed that oral administration of PE, ω-3, or both (mix)
prevented hippocampus-dependent short-term memory deficits induced by
D-galactose (P < 0.05). This effect was accompanied by the modulation of gut
microbiota, altered by the treatment. PE and the mix increased the expression of
antioxidative and neurogenesis markers, such as catalase and doublecortin, in
hippocampus (P < 0.05 for both). Moreover, ω-3 and the mix showed a higher ω-3
amounts (P < 0.05) and EPA-derived 18- hydroxyeicosapentaenoic acid (P < 0.001)
in prefrontal cortex. These changes may contribute to the improvement in memory.
CONCLUSIONS: These results suggest that the mix of PE and ω-3 could be more
efficient at attenuating age-related cognitive decline than individual
supplementations because it targeted, in mice, the different pathways impaired
with aging.
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.
DOI: 10.1016/j.tjnut.2024.09.015
PMID: 39332773 [Indexed for MEDLINE]
Conflict of interest statement: Conflict of interest DG, coordinator of Silver
Brain Food project, reports financial support was provided by Public Investment
Bank France. MM, LP, and DG are funded by Activ’Inside. Activ’Inside employees
were mainly involved in the design of the study and in the choice of extract
doses to be used, based on previous research and their expertise on grape and
blueberry polyphenols extract and saffron extract. The other authors report no
conflicts of interest.