Puerarin alleviates cognitive impairment and oxidative stress in APP/PS1 transgenic mice.

Abstract

Increasing evidence demonstrates that β-amyloid (Aβ) elicits oxidative stress, which contributes to the pathogenesis and disease progression of Alzheimer's disease (AD). Thus, there is interest in developing antioxidant therapies for the prevention/treatment of cognitive decline during AD. We reported previously that puerarin has antioxidative properties in vitro. Therefore, the aim of the present study was to determine whether puerarin improves cognitive function and reduces oxidative stress in amyloid precursor protein/presenilin-1 (APP/PS1) mice, a well established AD mouse model, and explore its potential mechanism. Our results show that oral administration of puerarin significantly ameliorates cognitive impairment in APP/PS1 mice assessed by the Morris water maze (MWM) test. This was accompanied by a significant decrease in the levels of lipid peroxidation (LPO) through, at least in part, induction of nuclear factor erythroid 2-related factor 2 (Nrf2) target gene heme oxygenase 1 (HO-1) in the hippocampus of APP/PS1 transgenic mice at 9 months of age, but without altering brain Aβ burden. Furthermore, puerarin significantly activated Akt, reduced activation of glycogen synthase kinase 3β (GSK-3β), and induced nuclear translocation of Nrf2 in the hippocampus of APP/PS1 mice but did not alter ERK1/2 phosphorylation. Thus, puerarin may improve cognitive performance in APP/PS1 mice through activation of the Akt/GSK-3β signaling pathway. These findings suggest that puerarin might be an attractive agent for prevention and treatment of cognitive impairment and dementia.

• Authors: Yanyan Zhou, Ning Xie, Libo Li, Yu Zou, Xiaojie Zhang, Miaoxian Dong
• Journal: The international journal of neuropsychopharmacology (Int J Neuropsychopharmacol) Vol. 17 Issue 4 Pg. 635-44 (Apr 2014) ISSN: 1469-5111 [Electronic] England
• PMID: 24345484 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Protein Precursor
• Isoflavones
• Presenilin-1
• Vasodilator Agents
• presenilin 1, mouse
• Glycogen Synthase Kinase 3
• puerarin

Topics

• Alzheimer Disease (drug therapy, metabolism)
• Amyloid beta-Protein Precursor (genetics)
• Animals
• Behavior, Animal (drug effects)
• Cognition Disorders (drug therapy, metabolism)
• Disease Models, Animal
• Glycogen Synthase Kinase 3 (metabolism)
• Hippocampus (drug effects, metabolism)
• Isoflavones (administration & dosage, pharmacology)
• Mice
• Mice, Transgenic
• Oxidative Stress (drug effects)
• Presenilin-1 (genetics)
• Vasodilator Agents (administration & dosage, pharmacology)