• Open Access

Hopeahainol A attenuates memory deficits by targeting β-amyloid in APP/PS1 transgenic mice

Authors

  • Xiaolei Zhu,

    1. Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
    2. Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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  • Lan Ye,

    1. Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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  • Huiming Ge,

    1. Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
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  • Ling Chen,

    1. Department of Physiology, Nanjing Medical University, Nanjing, China
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  • Nan Jiang,

    1. Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
    2. Department of Physiology, Nanjing Medical University, Nanjing, China
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  • Lai Qian,

    1. Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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  • Lingling Li,

    1. Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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  • Rong Liu,

    1. Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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  • Shen Ji,

    1. Department of Traditional Chinese Medicine, Shanghai Institute of Food & Drug Controls, Shanghai, China
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  • Su Zhang,

    1. Department of Traditional Chinese Medicine, Shanghai Institute of Food & Drug Controls, Shanghai, China
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  • Jiali Jin,

    1. Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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  • Dening Guan,

    1. Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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  • Wei Fang,

    1. Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
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  • Renxiang Tan,

    Corresponding author
    1. Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
    • Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
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  • Yun Xu

    Corresponding author
    1. Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
    2. Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
    • Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
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Correspondence

Yun Xu, Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 ZhongShan Road, Nanjing City, Jiangsu Province, 210008, China. Tel./fax: +86 25 8310 5208; e-mail:xuyun20042001@yahoo.com.cn or

Renxiang Tan, Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing City, Jiangsu Province, 210093, China. Tel./fax: +86 25 8368 6559; e-mail: rxtan@nju.edu.cn

Summary

Increasing evidence demonstrates that amyloid beta (Aβ) elicits mitochondrial dysfunction and oxidative stress, which contributes to the pathogenesis of Alzheimer's disease (AD). Identification of the molecules targeting Aβ is thus of particular significance in the treatment of AD. Hopeahainol A (HopA), a polyphenol with a novel skeleton obtained from Hopea hainanensis, is potentially acetylcholinesterase-inhibitory and anti-oxidative in H2O2-treated PC12 cells. In this study, we reported that HopA might bind to Aβ1–42 directly and inhibit the Aβ1–42 aggregation using a combination of molecular dynamics simulation, binding assay, transmission electron microscopic analysis and staining technique. We also demonstrated that HopA decreased the interaction between Aβ1–42 and Aβ-binding alcohol dehydrogenase, which in turn reduced mitochondrial dysfunction and oxidative stress in vivo and in vitro. In addition, HopA was able to rescue the long-term potentiation induction by protecting synaptic function and attenuate memory deficits in APP/PS1 mice. Our data suggest that HopA might be a promising drug for therapeutic intervention in AD.

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