Ellagic acid ameliorates learning and memory impairment in APP/PS1 transgenic mice via inhibition of β‑amyloid production and tau hyperphosphorylation

Zhong,Lili; Liu,Hong; Zhang,Weijia; Liu,Xu; Jiang,Bo; Fei,Hongxin; Sun,Zhongren

doi:10.3892/etm.2018.6860

Ellagic acid ameliorates learning and memory impairment in APP/PS1 transgenic mice via inhibition of β‑amyloid production and tau hyperphosphorylation

Authors:
- Lili Zhong
- Hong Liu
- Weijia Zhang
- Xu Liu
- Bo Jiang
- Hongxin Fei
- Zhongren Sun
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Affiliations: Department of Pathology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150001, P.R. China, Postdoctoral Program, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P.R. China, Second Department of Orthopedic Surgery, Harbin First Hospital, Harbin, Heilongjiang 150010, P.R. China, Experimental Center, School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P.R. China, Drug Safety Evaluation Center, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P.R. China, Department of Pathology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Key Laboratory of Acupuncture Clinical Neurobiology (Encephalopathy), Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P.R. China
Published online on: October 15, 2018 https://doi.org/10.3892/etm.2018.6860
Pages: 4951-4958
Copyright: © Zhong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

β‑amyloid (Aβ) aggregation and tau hyperphosphorylation are considered to be the primary pathological hallmarks of Alzheimer's disease (AD). Targeted inhibition of these pathological processes may provide effective treatments for AD. Accumulating evidence has demonstrated that ellagic acid (EA) exerts neuroprotective effects in several diseases. The present study investigated the effects of EA on AD‑associated learning and memory deficits on APP/PS1 double transgenic mice and the underlying mechanisms. APP/PS1 mice or wild‑type C57BL/6 mice were intragastrically administered EA (50 mg/kg/day) or vehicle for 60 consecutive days. The learning and memory abilities of mice were investigated using the Morris water maze test. Hippocampal regions were examined for the presence of amyloid plaques, neuronal apoptosis and tau phosphorylation. Expression levels of APP, Aβ, RAC‑αserine/threonine‑protein kinase and glycogen synthase kinase (GSK)3β in the hippocampus were determined by western blot analysis and ELISA. The results demonstrated that EA treatment ameliorated spatial learning and memory impairment in APP/PS1 mice and significantly reduced neuronal apoptosis and Aβ deposition in the hippocampus (P<0.05 and P<0.01). In addition, EA significantly inhibited the hyperphosphorylation of tau and significantly decreased the activity of glycogen synthase kinase (GSK)3β (P<0.01), which is involved in tau phosphorylation. Overall, these findings indicated that the beneficial effects of EA on AD‑associated cognitive impairments may be attributed to the inhibition of Aβ production and tau hyperphosphorylation, and its beneficial action may be mediated in part, by the RAC‑α serine/threonine‑protein kinase/GSK3β signaling pathway.

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