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

## TL;DR

This study shows that combining plant extracts and omega-3 improves memory and brain health in old mice by reducing inflammation and improving gut bacteria.

## Contribution

The novel finding is that combining plant extracts and omega-3 provides better long-term memory protection and gut microbiota improvement than either alone.

## Key findings

- Combined plant extracts and omega-3 improved long-term memory in aged mice.
- The combination reduced hippocampal inflammation and oxidative stress.
- It also enhanced synaptic plasticity and improved gut microbiota composition.

## Abstract

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.

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.

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.

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.

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.

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•The combination of plant extracts and omega-3 prevent age-related cognitive decline.•Combined supplementation reduces hippocampal inflammation and oxidative stress.•The combination upregulates synaptic development signalling pathways in hippocampus.•The combination beneficially modulates gut microbiota linked to cognitive functions.

The combination of plant extracts and omega-3 prevent age-related cognitive decline.

Combined supplementation reduces hippocampal inflammation and oxidative stress.

The combination upregulates synaptic development signalling pathways in hippocampus.

The combination beneficially modulates gut microbiota linked to cognitive functions.