Allantoin ameliorates amyloid β-peptide-induced memory impairment by regulating the PI3K/Akt/GSK-3β signaling pathway in rats

Alzheimer's disease (AD) is a brain disease that causes problems in memory, thinking, and behavior. Allantoin has been shown to have antioxidant, anti-inflammatory, and neuroprotective effects. In this study, we aimed to investigate the effect and mechanism of action of allantoin on AD-related memory impairment. We investigated the effect of allantoin on an amyloid β 1–42 peptide (Aβ 1–42 )-induced AD model in rats and evaluated its memory-enhancing effect using the Morris water maze test. Pathological changes in the hippocampus and cortex were examined by hematoxylin-eosin staining. The expression of the phosphorylated Tau protein and PI3K/Akt/GSK-3β signaling pathway was analyzed by western blotting. The results of the water maze test showed that after treatment with allantoin, the rats could reduce their swimming time and travel distances to find the platform. Allantoin treatment also increased the time spent in the quadrant in which the platform was located. Histological assessment showed that Aβ 1–42 could cause morphological alterations in nerve cells in the hippocampal CA1 region, and that allantoin could repair the damage to these cells. Western blotting revealed that allantoin treatment increased the expression of p-PI3K, p-Akt, and p-GSK-3β and decreased p-Tau in the hippocampus and cortex of rats. These effects were inhibited by LY294002. These findings showed that allantoin could improve cognitive impairment in Aβ 1–42 -induced rats by activating the PI3K/Akt/GSK-3β signaling pathway to reduce abnormal hyperphosphorylation of Tau. Thus, allantoin may be a potential therapeutic agent for neurodegenerative diseases. • Allantoin had a tendency to improve the cognitive impairment of Aβ-induced Alzheimer's disease in rats. • Allantoin might inhibit tau protein phosphorylation by activating the PI3K/Akt/GSK-3β signaling pathway in the hippocampus and cortex. • Allantoin might be a potential therapeutic agent for this neurodegenerative disease.