# Preventive Effect of Probiotic Leuconostoc mesenteroides H40 Against Cognitive Disorder by Anti-Inflammatory, Synaptic Plasticity Regulation, and Antioxidant Effects

**Authors:** Na-Kyoung Lee, Yunjung Lee, Minhye Won, Nayeong Kim, Eunju Park, Hyun-Dong Paik

PMC · DOI: 10.3390/antiox14050565 · Antioxidants · 2025-05-08

## TL;DR

This study shows that the probiotic Leuconostoc mesenteroides H40 helps prevent cognitive disorders in mice by reducing inflammation, improving brain plasticity, and fighting oxidative stress.

## Contribution

The novel contribution is demonstrating the preventive effects of live L. mesenteroides H40 on cognitive disorders through multiple neuroprotective mechanisms.

## Key findings

- L. mesenteroides H40 reduced cognitive impairment in mice in a concentration-dependent manner.
- The probiotic decreased inflammatory markers like TNF-α, IL-1β, and PGE2 while increasing acetylcholine and BDNF levels.
- Antioxidant enzyme activity was enhanced, suggesting protection against oxidative stress in the brain.

## Abstract

Live Leuconostoc mesenteroides H40 has been reported to have probiotic properties; however, the effect of its live probiotic form on cognitive ability has not been reported. This study investigated modulatory effects of the probiotic L. mesenteroides H40 in an ICR mouse model (male) of cognitive disorders. Cognitive disorders were induced in mice by the addition of scopolamine (1 mg/kg/day) with donepezil (2 mg/kg/day) as a medicinal control. L. mesenteroides H40 significantly attenuated scopolamine-induced cognitive disorder in the novel object recognition and Y-maze tests in a concentration-dependent manner. L. mesenteroides H40 decreased amyloid β levels, but increased β-secretase levels. The mRNA expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 significantly decreased following L. mesenteroides H40 treatment. Additionally, TNF-α, IL-1β, and PGE2 protein expression was decreased. Acetylcholine, acetylcholinesterase, choline acetyltransferase, brain-derived neurotrophic factor (BDNF), and cAMP response element-binding protein (CREB) levels were increased in the brain tissues. The antioxidant effects of superoxide dismutase, catalase, and glutathione peroxidase were also alleviated. We demonstrated that L. mesenteroides H40 exhibits neuroprotective effects through anti-inflammatory, synaptic plasticity regulation, and antioxidant effects. Thus, the probiotic L. mesenteroides H40 could be used as a prophylactic functional food for cognitive disorders.

## Linked entities

- **Genes:** NOS2 (nitric oxide synthase 2) [NCBI Gene 4843], COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513], BDNF (brain derived neurotrophic factor) [NCBI Gene 627], CREB1 (cAMP responsive element binding protein 1) [NCBI Gene 1385]
- **Proteins:** TNF (tumor necrosis factor), IL1B (interleukin 1 beta), ptges2.L (prostaglandin E synthase 2 L homeolog), BDNF (brain derived neurotrophic factor), CREB1 (cAMP responsive element binding protein 1)
- **Chemicals:** scopolamine (PubChem CID 5184), donepezil (PubChem CID 3152)

## Full-text entities

- **Diseases:** Inflammatory (MESH:D007249), Cognitive Disorder (MESH:D003072)
- **Chemicals:** donepezil (MESH:D000077265), Acetylcholine (MESH:D000109), scopolamine (MESH:D012601), H40 (-)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Halomonas sp. 40 (species) [taxon 223901], Leuconostoc mesenteroides (species) [taxon 1245]

## Full text

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## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12108271/full.md

## References

40 references — full list in the complete paper: https://tomesphere.com/paper/PMC12108271/full.md

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Source: https://tomesphere.com/paper/PMC12108271