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Antioxidative and Anti-Apoptotic Roles of Silibinin in Reversing Learning and Memory Deficits in APP/PS1 Mice

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Abstract

Silibinin has been widely used to treat liver diseases due to its antioxidant activity. However, the effects of silibinin on the central nervous system have not been thoroughly investigated. The pathological hallmarks of Alzheimer’s disease are the accumulation of amyloid β protein, development of neurofibrillary tangles and increased oxidative stress, which ultimately lead to irreversible neuronal loss and cognitive impairment. Our findings show that silibinin ameliorated memory impairments in APP/PS1 mice in the Morris water maze via suppression of oxidative stress and inhibition of apoptosis. Treatment with silibinin reduced malondialdehyde content level and increased glutathione and superoxide dismutase activity in APP/PS1 mice. A terminal deoxynucleotidyl transferase dUTP nick end labeling assay revealed an anti-apoptotic effect of silibinin. Silibinin suppressed the activation of caspase-3 by inhibiting Jun N-terminal kinase phosphorylation and the downstream hippocampal Bax/Bcl-2 ratio. Silibinin treatment significantly increased levels of synaptophysin and PSD95 in APP/PS1 transgenic mice. These results suggest that silibinin could be a potential therapeutic agent for the treatment of Alzheimer’s disease.

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Acknowledgements

This study was supported by Subject of Liaoning natural science fund (20170540880), Liaoning education department project (L2014409), Shenyang science and Technology Bureau subject of China (F13-220-9-27).

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Authors and Affiliations

  1. The Eleventh People’s Hospital of Shenyang, Shenyang, 110101, People’s Republic of China

    Dafeng Bai

  2. Department of Pharmacology, Shenyang Medical Colleges, Shenyang, 110034, People’s Republic of China

    Ge Jin, Shiliang Yin, Dan Zou, Qiwen Zhu, Zhihang Yang, Xuan Liu, Lizheng Ren, Yifeng Sun & Shiming Gan

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  1. Dafeng Bai
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  2. Ge Jin
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Correspondence to Ge Jin.

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Bai, D., Jin, G., Yin, S. et al. Antioxidative and Anti-Apoptotic Roles of Silibinin in Reversing Learning and Memory Deficits in APP/PS1 Mice. Neurochem Res 42, 3439–3445 (2017). https://doi.org/10.1007/s11064-017-2389-3

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  • DOI: https://doi.org/10.1007/s11064-017-2389-3

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