Journal Article

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

Liao, Han-Wei, Chen, Yu-Hsiang, Tsai, Hui-Yun, Ho, Chi-Tang, Qiu, Jing, Chang, Chi-I, Chen, Yu-Kuo

2026

Overview

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.

• Publisher: MDPI AG
• Subject: Alzheimer Disease - chemically induced / Alzheimer Disease - drug therapy / Alzheimer Disease - metabolism / Alzheimer's disease / Amyloid beta-Peptides - metabolism / Analysis / Animals / Antioxidants - pharmacology / Anxiety / Behavior / Cognitive ability / Cognitive Dysfunction - chemically induced / Cognitive Dysfunction - drug therapy / Cognitive Dysfunction - metabolism / Diabetes / Disease Models, Animal / Drinking water / Glutathione / Glycogen Synthase Kinase 3 beta - metabolism / Hippocampus - drug effects / Hippocampus - metabolism / Hippocampus - pathology / Inflammation / Kinases / Male / Memory / Metabolism / Metabolites / Mice / Mice, Inbred C57BL / Neuroinflammatory Diseases - chemically induced / Neuroinflammatory Diseases - drug therapy / Neuroinflammatory Diseases - metabolism / Neurons / Neuroprotective Agents - pharmacology / Older people / Oxidative stress / Pathology / Phosphatidylinositol 3-Kinases - metabolism / Phosphorylation / Phosphorylation - drug effects / Physiology / Proto-Oncogene Proteins c-akt - metabolism / Pyruvaldehyde - adverse effects / Pyruvaldehyde - toxicity / Signal Transduction - drug effects / tau Proteins - metabolism