# Anti-Inflammatory Peptide Prevents Aβ25–35-Induced Inflammation in Rats via Lipoxygenase Inhibition

**Authors:** Yudhishthir Yadav, Masroor Anwar, Hanuman Sharma, Suman Jain, Uma Sharma, Partha Haldar, Aparajit B. Dey, Sharmistha Dey

PMC · DOI: 10.3390/cells14130957 · Cells · 2025-06-23

## TL;DR

A peptide called YWCS reduces inflammation and improves cognitive function in rats with Alzheimer's-like symptoms by inhibiting lipoxygenase enzymes.

## Contribution

YWCS is shown to be a novel therapeutic candidate for Alzheimer's disease by targeting LOX enzymes and improving cognitive and inflammatory markers.

## Key findings

- YWCS improved cognitive performance in multiple behavioral tests in AD rats.
- YWCS reduced the expression of LOX, Aβ, and p-Tau181 in the hippocampus of AD rats.
- Serum LOX levels in AD rats were significantly reduced after YWCS treatment.

## Abstract

Neuroinflammation, triggered by lipoxygenase (LOX), contributes to Alzheimer’s disease (AD) progression. Overexpression of LOX-5 in patients with AD serum highlights its role. This study assessed the efficacy of the LOX-inhibitor-peptide YWCS in an AD rat model induced by Aβ25–35 injection. Cognitive tests, magnetic resonance imaging (MRI) scans, and molecular analyses were conducted. YWCS treatment significantly improved cognitive function, as evidenced by improved performance in the open field, novel object recognition, elevated plus maze, and Morris water maze tests. MRI scans revealed hippocampal shrinkage in AD rats and no changes were observed from YWCS treatment. Molecular analysis revealed altered expression of LOX-5, LOX-12, Aβ, γ-secretase components, p-Tau181, Akt, p-Akt, and p53 in AD rats. Immunofluorescence staining confirmed increased expression of LOX, Aβ, and p-Tau181 in the hippocampus of AD rats, which was reduced by YWCS treatment. Serum LOX levels were elevated in AD rats and significantly decreased after YWCS treatment, aligning with previous findings in human AD patients and AD cell models. YWCS offered improvements in behavioral and inflammatory marker regulation and also prevented progression of the disease, as shown by MRI results. These results suggest that YWCS, by targeting LOX, has the potential to be a promising therapeutic agent for AD.

## Linked entities

- **Proteins:** LOX (lysyl oxidase), LOX5 (PLAT/LH2 domain-containing lipoxygenase family protein), lox12 (linoleate 9S-lipoxygenase12), ab (abrupt), AKT1 (AKT serine/threonine kinase 1), Akt (Akt kinase), TP53 (tumor protein p53)
- **Diseases:** Alzheimer’s disease (MONDO:0004975), AD (MONDO:0004975)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Akt1 (AKT serine/threonine kinase 1) [NCBI Gene 24185] {aka Akt}, p53-ps (Wistar clone pR53P1 p53 pseudogene) [NCBI Gene 301300], App (amyloid beta precursor protein) [NCBI Gene 54226] {aka Abeta}
- **Diseases:** Inflammation (MESH:D007249), Neuroinflammation (MESH:D000090862), AD (MESH:D000544)
- **Chemicals:** Anti (-)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12249324/full.md

## References

52 references — full list in the complete paper: https://tomesphere.com/paper/PMC12249324/full.md

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Source: https://tomesphere.com/paper/PMC12249324