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Picrorhiza kurroa Prevents Memory Deficits by Inhibiting NLRP3 Inflammasome Activation and BACE1 Expression in 5xFAD Mice

  • Namkwon Kim
  • Jimin Do
  • In Gyoung Ju
  • Seung Ho Jeon
  • Jong Kil LeeEmail author
  • Myung Sook OhEmail author
Original Article

Abstract

One of the most significant pathologies of Alzheimer’s disease (AD), an irreversible and progressive neurodegenerative disease that causes cognitive impairment, is the neuroinflammation facilitating the accumulation of amyloid-β (Aβ) peptide. Hence, the inhibition of abnormal neuroinflammatory response is considered a promising therapeutic approach for AD. Picrorhiza kurroa Bentham, Scrophulariae (PK) is a medicinal herb that has been traditionally used for the treatment of various diseases, including inflammation. This study aims to report the significance of PK treatment in markedly improving spatial learning memory and dramatically decreasing Aβ levels in Tg6799 mice, also known 5xFAD mice, which have five familial AD (FAD) mutations. Remarkably, these effects correlated with reversal of disease-related microglial neuroinflammation, as evidenced by shifting microglia phenotypes from the inflammatory form to the anti-inflammatory form and inhibiting the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 3 inflammasome activity. Moreover, PK administration induced silent information regulator type1/peroxisome proliferator-activated receptor-γ signaling, resulting in a decrease of β-secretase 1 (BACE1) expression, which involved in Aβ production. Overall, this study suggests that PK exhibits a neuroprotective effect by inducing alternative activation of microglia and downregulating the BACE1 expression, thereby ameliorating the disease pathophysiology and reversing the cognitive decline related to Aβ deposition in AD mice.

Key Words

Alzheimer’s disease Picrorhiza kurroa amyloid-beta inflammation NLRP3 inflammasome β-secretase 1 

Notes

Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2018R1D1A1B07050547), the Medical Research Center Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT (NRF-2017R1A5A2014768), and the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry (IPET) through High Value-Added Food Technology Development Program, funded by Ministry of Agriculture Food and Rural Affairs (MAFRA) (318027-04).

Required Author Forms

Disclosure forms provided by the authors are available with the online version of this article.

Author Contributions

N.K.K. and J.M.D. performed the experiments, analyzed the data, and prepared the manuscript. I.G.J. and S.H.J. performed the animal study. M.S.O. and J.K.L. interpreted the data and reviewed the manuscript. M.S.O. designed the study and wrote the manuscript.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2019

Authors and Affiliations

  1. 1.Department of Life and Nanopharmaceutical Sciences, Graduate SchoolKyung Hee UniversitySeoulRepublic of Korea
  2. 2.Department of Biomedical Science and Technology, Graduate SchoolKyung Hee UniversitySeoulRepublic of Korea
  3. 3.Department of Fundamental Pharmaceutical Science, Graduate SchoolKyung Hee UniversitySeoulRepublic of Korea
  4. 4.Department of Pharmacy, College of PharmacyKyung Hee UniversitySeoulRepublic of Korea
  5. 5.Department of Oriental Pharmaceutical Science, College of PharmacyKyung Hee UniversitySeoulRepublic of Korea

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