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.

Nrf2—a therapeutic target for the treatment of neurodegenerative diseases

“…CDDO-methylamide (CDDO-MA) improved memory and decreased plaques, Aβ(1-42), and markers of oxidative stress in the Tg19959 mice [86]. Puerarin, a phytoestrogen with antioxidant properties, was shown to improve the phenotype of APP/PS1 mice [87]. The effect was attributed to preventing the activation of GSK3β, thus preventing proteasomal degradation of Nrf2 through the β-TrCP pathway.…”

Melanocyte‐protective effect of afzelin is mediated by the Nrf2‐ARE signalling pathway via GSK‐3β inactivation

“…They have been demonstrated as regulators of the GSK‐3β‐associated signalling pathway that is involved in Nrf2 activation. The flavonoid, puerarin, induces the nuclear translocation of Nrf2 and stimulates the expression of Nrf2‐dependent genes in APP/PS1 transgenic mice and neuron cells via the activation of the phosphatidylinositol 3‐kinase (PI3K)/GSK‐3β pathway . Another flavonoid, quercetin, improves hippocampus‐dependent learning and memory in mice via the PI3K/protein kinase B (AKT)/Nrf2 pathway .…”

Neurotherapeutic Effects of Pueraria mirifica Extract in Early- and Late-Stage Cognitive Impaired Rats

“…In addition to a weak estrogenic activity (Rachoń et al , ; Malaivijitnond et al , ; this study), PU has also been reported to elicit a strong anti‐oxidant capacity on neuronal cells (Mahdy et al , ). The reduced level of cognitive impairment in APP/presenilin‐1 mice induced by PU was likely because of the significant decrease in the levels of lipid peroxidation without any changes in Aβ deposition (Zhou et al , ). Taken together, these results suggest that PU ablates neurodegenerative disease primarily by a reduction in the production of neurofibrillary tangles and may possibly not involve the amyloid pathway.…”