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Amentoflavone Ameliorates Aβ1–42-Induced Memory Deficits and Oxidative Stress in Cellular and Rat Model

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Abstract

Alzheimer’s disease (AD), a progressive neurodegenerative disease of the central nervous system, is the most common cause of senile dementia. This study aimed to investigate whether amentoflavone (AF), a biflavonoid compound, could exert neuroprotective activities against AD. The AD model was established by the intracranial injection of amyloid-beta (Aβ) in rat models. The effect of AF on cognitive function was examined using the Morris water maze test. Cell survival and apoptosis in the hippocampal region in an animal model were detected using Nissl staining and a terminal deoxynucleotidyl transferased UTP nick-end labeling assay, respectively. The levels of oxidant enzymes were determined by enzyme-linked immunosorbent assay. Signaling molecule expressions were examined by western blotting. Our results showed that AF significantly attenuated Aβ-induced deficits in neurological functions as well as neuronal cell death and apoptosis in the hippocampal region. Moreover, our findings revealed that AF increased nuclear factor erythroid 2-related factor 2 (Nrf2) expression and translocation and activated AMP-activated protein kinase (AMPK) signaling. In a cellular model of AD established by exposing PC12 cells to Aβ, our results provided further evidence that the neuroprotective activities of AF were mediated by modulating Nrf2 through AMPK/glycogen synthase kinase 3 beta signaling. AF exerts a protective effect against Aβ1–42-induced neurotoxcicity by inducing Nrf2 antioxidant pathways via AMPK signaling activation, which provided experimental evidence that AF might provide a clinical benefit to patients with AD.

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Acknowledgements

The study was supported by Natural Science Foundation of Shandong Province (zr2014hl034).

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Authors and Affiliations

  1. Department of Traditional Chinese Medicine, Shandong Qianfoshan Hospital, 16766 Jingshi Road, Jinan, 250014, China

    Chao Chen, Guangqing Cheng, Xiaoni Yang, Ningning Zhao & Ran Shi

  2. Department of Neurology, The Affiliated Hiser Hospital of Qingdao University, Qingdao, China

    Bin Li

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  1. Chao Chen
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  2. Bin Li
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Correspondence to Ran Shi.

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Chen, C., Li, B., Cheng, G. et al. Amentoflavone Ameliorates Aβ1–42-Induced Memory Deficits and Oxidative Stress in Cellular and Rat Model. Neurochem Res 43, 857–868 (2018). https://doi.org/10.1007/s11064-018-2489-8

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