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Gelsemine, a natural alkaloid extracted from Gelsemium elegans Benth. alleviates neuroinflammation and cognitive impairments in Aβ oligomer-treated mice

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Abstract

Introduction

Gelsemine is a natural alkaloid extracted from Gelsemium elegans Benth., a traditional Chinese medicinal herb. Gelsemine has been shown to penetrate the brain, and could produce neurological activities, such as anxiolytic and neuralgia-alleviating effects, suggesting that this natural compound might be used for treating nervous system diseases.

Results

In this study, we have found, for the first time, that gelsemine at low concentrations (5–10 μg/kg) significantly alleviated cognitive impairments induced by β-amyloid (Aβ) oligomer, a main neurotoxin of Alzheimer’s disease (AD). In addition, gelsemine substantially prevented Aβ oligomer-induced over-activation of microglia and astrocytes, indicating that gelsemine might reduce AD-related gliosis. Consistently, gelsemine inhibited the over-expression of pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in the brain of mice. Moreover, gelsemine largely increased the expression of pSer9-glycogen synthase kinase-3β (GSK3β), and decreased the hyper-phosphorylation of tau protein as evidenced by Western blotting analysis. Furthermore, gelsemine prevented Aβ oligomer-induced reduction of PSD-95, a representative post-synaptic protein.

Conclusion

All these results directly demonstrated the anti-Aβ oligomer neuroprotective properties of gelsemine, opening a novel perspective for the development of gelsemine-based therapeutics against Aβ-associated neurodegeneration disorders, including AD in particular.

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Abbreviations

Aβ:

β-Amyloid

AD:

Alzheimer’s disease

DMSO:

Dimethyl-sulfoxide

ELISA:

Enzyme-linked immunosorbent assay

GFAP:

Glial fibrillary acidic protein GSK3β, glycogen synthase kinase-3β

HFIP:

1,1,1,3,3,3-hexafluoro-2-propanol

ICR:

Institute of Cancer Research

IL-1β:

Interleukin-1β

IL-6:

Interleukin-6

MWM:

Morris water maze

NFT:

Neurofibrillary tangles

NIH:

National Institutes of Health

OFT:

Open filed test

PBS:

Phosphate-buffered saline

RAM:

Radial arm maze

TNF-α:

Tumor necrosis factor-α

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Funding

This research was funded by the National Natural Science Foundation of China (81870853), Ningbo Sci & Tech Project for Common Wealth (2017C50042), Zhejiang Key Laboratory of Pathophysiology (201804), Open Project Program of State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science & Technology (SKLFNS-KF-201806), Ningbo municipal innovation team of life science and health (2015C110026), LiDakSum Marine Biopharmaceutical Development Fund, and the K. C. Wong Magna Fund in Ningbo University.

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Authors and Affiliations

  1. Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, People’s Republic of China

    Liping Chen, Hanbo Pan, Yujing Bai & Wei Cui

  2. School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, People’s Republic of China

    Huiqin Li, Wen Yang, Zhi-Xiu Lin & Yan-Fang Xian

  3. Brain Research Centre, School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, People’s Republic of China

    Zhi-Xiu Lin & Yan-Fang Xian

  4. Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, People’s Republic of China

    Zhi-Xiu Lin

  5. Department of Physiology, School of Medicine, Ningbo University. Ningbo, Ningbo, 315211, People’s Republic of China

    Wei Cui

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  1. Liping Chen
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  2. Hanbo Pan
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Correspondence to Wei Cui or Yan-Fang Xian.

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Chen, L., Pan, H., Bai, Y. et al. Gelsemine, a natural alkaloid extracted from Gelsemium elegans Benth. alleviates neuroinflammation and cognitive impairments in Aβ oligomer-treated mice. Psychopharmacology 237, 2111–2124 (2020). https://doi.org/10.1007/s00213-020-05522-y

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