Preventing effect of plant extracts and omega-3 on age-related cognitive decline in male mice

Marie Martin, Adrien Peltier, Heena Vanmalibhai Lad, Aline Foury, Charlotte Madore-Delpech, Line Pourtau, David Gaudout, Sophie Layé, Véronique Pallet, Anne-Laure Dinel, Corinne Joffre
Brain, Behavior, & Immunity - Health. 2025-11-01; 49: 101127
DOI: 10.1016/j.bbih.2025.101127

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https://www.bordeaux-neurocampus.fr/12414

1. Brain Behav Immun Health. 2025 Oct 23;49:101127. doi:
10.1016/j.bbih.2025.101127. eCollection 2025 Nov.

Preventing effect of plant extracts and omega-3 on age-related cognitive decline
in male mice.

Martin M(1)(2), Peltier A(1)(3), Lad HV(1), Foury A(1), Madore-Delpech C(1),
Pourtau L(2), Gaudout D(2), Layé S(1), Pallet V(1), Dinel AL(1)(3), Joffre C(1).

Author information:
(1)Université Bordeaux, INRAE, Bordeaux INP, Nutrineuro, UMR 1286, 33076,
Bordeaux, France.
(2)Activ’Inside, 12 route de Beroy, ZA Du Grand Cazeau, 33750,
Beychac-et-Caillau, France.
(3)NutriBrain Research and Technology Transfer, NutriNeuro, 33076, Bordeaux,
France.

BACKGROUND: Aging is associated with cognitive decline, accompanied by
neuroinflammation, oxidative stress, impaired synaptic plasticity, and gut
microbiota dysbiosis. Nutritional interventions, specifically those rich in
polyphenols, carotenoids, and omega-3 (om-3) fatty acids, have demonstrated
potential benefits in preventing age-related cognitive decline. This study
investigates the combined effects of plant extracts (PE) including polyphenols
and carotenoids, and fish oil containing om-3 on cognitive function and
underlying biological processes in aged mice.
OBJECTIVES: To assess the impact of PE and om-3, alone and in combination, on
age-related cognitive decline, especially on memory outcomes and to highlight
mechanisms involved in these effects.
METHODS: 17-month-old male C57BL/6 J mice were divided into control and
supplemented groups (PE, om-3, and PE + om-3). A group of young mice was used
for positive control. Behavioral assessments, including the Elevated Plus Maze
(EPM) for anxiety-like behavior, the Object Location Test (OLT) for short-term
memory and the Morris Water Maze (MWM) for long-term memory, were conducted. RNA
sequencing, fatty acid and oxylipin concentrations analysis and gut microbiota
analysis were used to explore molecular changes and microbial diversity.
RESULTS: All supplementations significantly improved short-term memory in the
OLT, while only PE and PE + om-3 prevented long-term memory deficits in the MWM.
All supplementations modulated gene expression, reducing inflammation, apoptosis
or oxidative stress markers in the hippocampus. PE + om-3 further enhanced
synaptic plasticity pathways and improved microbiota composition by decreasing
harmful bacteria associated with cognitive decline.
CONCLUSION: Combined PE and om-3 supplementation could provide a complementary
approach to combat age-related cognitive decline, highlighting its potential in
promoting long-term neuroprotection through modulation of inflammation,
oxidative stress and gut microbiota.

© 2025 The Authors.

DOI: 10.1016/j.bbih.2025.101127
PMCID: PMC12596225
PMID: 41216177

Conflict of interest statement: The authors declare the following financial
interests/personal relationships which may be considered as potential competing
interests: Marie Martin reports financial support was provided by Activ’Inside
SAS. Line Pourtau reports financial support was provided by Activ’Inside SAS.
David Gaudout reports financial support was provided by Activ’Inside SAS. If
there are other authors, they declare that they have no known competing
financial interests or personal relationships that could have appeared to
influence the work reported in this paper.

Auteurs Bordeaux Neurocampus