# Propyl Gallate Attenuates Methylglyoxal-Induced Alzheimer-like Cognitive Deficits and Neuroinflammation in Mice

## TL;DR

Propyl gallate, a food additive, protects mice from cognitive decline and brain inflammation caused by methylglyoxal, a compound linked to diabetes and Alzheimer's.

## Contribution

This study demonstrates propyl gallate's neuroprotective effects against methylglyoxal-induced Alzheimer-like symptoms in mice.

## Key findings

- Propyl gallate improved spatial learning and memory in mice exposed to methylglyoxal.
- Propyl gallate reduced hippocampal damage, tau hyperphosphorylation, and amyloid-β accumulation.
- Propyl gallate modulated neuroinflammatory responses and survival signaling pathways affected by methylglyoxal.

## Abstract

Methylglyoxal (MG), a reactive dicarbonyl metabolite associated with diabetes and metabolic disorders, contributes to carbonyl stress, neuroinflammation, and Alzheimer-like neurodegeneration. This study investigated the neuroprotective effects of propyl gallate (PG), a phenolic antioxidant widely used as a food additive, against MG-induced cognitive impairment in mice. Male C57BL/6J mice were exposed to 1% MG in drinking water for eight weeks and orally administered PG (20, 40, or 100 mg/kg/d). Behavioral tests demonstrated that PG significantly improved spatial learning and recognition memory and alleviated anxiety-like behavior induced by MG. Histological and biochemical analyses revealed that PG reduced hippocampal neuronal damage, suppressed tau hyperphosphorylation and amyloid-β (Aβ) accumulation, and attenuated the overexpression of pro-inflammatory cytokines TNF-α and IL-6. Furthermore, PG increased PI3K expression and Akt phosphorylation while reducing activation of GSK-3β, counteracting the MG-induced suppression of this pathway and aligning with reduced tau hyperphosphorylation. These findings indicate that PG protects against MG-related cognitive dysfunction through modulation of neuroinflammatory responses and survival-related signaling pathways, highlighting its potential as a neuroprotective dietary antioxidant for metabolic stress-associated neurodegenerative disorders.