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Schisandrin Inhibits NLRP1 Inflammasome-Mediated Neuronal Pyroptosis in Mouse Models of Alzheimer’s Disease

Authors Li Q, Wang Q, Guan H, Zhou Y, Liu L

Received 27 August 2020

Accepted for publication 24 December 2020

Published 29 January 2021 Volume 2021:17 Pages 261—268

DOI https://doi.org/10.2147/NDT.S279147

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Jun Chen


Quan Li,1 Qi Wang,2 Huibo Guan,3 Yanyan Zhou,2 Li Liu4

1Department of Organs, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang, People’s Republic of China; 2Teaching and Research Department of Basic Theory of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang, People’s Republic of China; 3Teaching and Research Department of Diagnostics of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang, People’s Republic of China; 4Department of Cardiovascular Diseases, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang, People’s Republic of China

Correspondence: Li Liu
Department of Cardiovascular Diseases, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, No. 26 Heping Road, Xiangfang District, Harbin 150040, Heilongjiang, People’s Republic of China
Tel +86 451-82111401 Ext 6975
Email liuli_hucm@126.com

Background: In recent years, schisandrin (SCH) was proved to improve Alzheimer’s Disease (AD). The aim of our study is to explore the effect of SCH on neuronal pyroptosis in the disease.
Methods: A Morris water maze test was performed to evaluate the spatial learning and memory retention of AD mouse. ELISA was fulfilled to examine the concentration of Aβ, IL-1β, and IL-18. Western blot was performed to detect the expression of apoptosis- and pyroptosis-related proteins. Besides, the neuronal apoptosis rate was examined using TUNEL assay. Immunohistochemistry was utilized to detect the activation of NLRP1 inflammasome.
Results: Here, AD mice have serious cognitive impairment. Meantime, Aβ was highly expressed in the brains of AD mice. SCH could effectively rescue the cognitive impairment in AD mice and impede the production of Aβ. Subsequently, we further demonstrated that SCH repressed neuronal apoptosis, pyroptosis-related proteins expression, and the activation of NLRP1 inflammasome in the hippocampus of AD mice. We also proved that Aβ induced neuronal apoptosis and pyroptosis in vitro. However, the effects of Aβ on neuronal apoptosis and pyroptosis were partly reversed by SCH treatment.
Conclusion: Overall, our data indicated that SCH improved cognitive impairment in AD mice through inhibition of NLRP1 inflammasome-mediated neuronal pyroptosis and neuronal apoptosis. Our works provided new evidence to support SCH acting as a potential treatment method in AD.

Keywords: Alzheimer’s disease, pyroptosis, schisandrin, apoptosis, traditional Chinese medicine

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