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Neurochemical Research

, Volume 43, Issue 2, pp 351–362 | Cite as

Eclalbasaponin II Ameliorates the Cognitive Impairment Induced by Cholinergic Blockade in Mice

  • Won Yong Jung
  • Haneul Kim
  • Se Jin Jeon
  • Hye Jin Park
  • Hyuck Jai Choi
  • Nam Jae Kim
  • Dong Hyun Kim
  • Dae Sik JangEmail author
  • Jong Hoon RyuEmail author
Original Paper

Abstract

Eclalbasaponin II derived from Eclipta prostrata L. (Asteraceae) has been reported to have anti-fibrotic, anti-bacterial and autophagic activities, but its effect on cognitive function has not been investigated. We studied the effect of eclalbasaponin II on cholinergic blockade-induced memory impairment in mice using the passive avoidance, Y-maze, and Morris water maze tasks. Eclalbasaponin II (10 or 20 mg/kg, p.o.) significantly ameliorated the cognitive dysfunction induced by scopolamine in the passive avoidance, Y-maze, and the Morris water maze tasks. To identify the mechanism of the memory-ameliorating effect of eclalbasaponin II, acetylcholinesterase (AChE) activity assay, Western blot analysis and electrophysiology were conducted. Eclalbasaponin II inhibited the AChE activity in ex vivo study, and the administration of eclalbasaponin II and its metabolite, echinocystic acid, increased the phosphorylation levels of memory-related signaling molecules, including protein kinase B (Akt) and glycogen synthase kinase-3β (GSK-3β), in the hippocampus. Although eclalbasaponin II did not affect hippocampal long term potentiation (LTP), echinocystic acid significantly enhanced hippocampal LTP formation (30 μM). These results suggest that eclalbasaponin II ameliorates cholinergic blockade-induced cognitive impairment via AChE inhibition, LTP formation and the activation of Akt-GSK-3β signaling, and that eclalbasaponin II may be a useful to treat cognitive impairment derived from cholinergic dysfunction.

Keywords

Eclalbasaponin II Learning and memory Long-term potentiation Protein kinase B Glycogen synthase kinase 3β 

Abbreviations

AChE

Acetylcholinesterase

AD

Alzheimer’s disease

Akt

Protein kinase B

ANOVA

One-way analysis of variance

Con

Control

DNZ

Donepezil

EPSPs

Evoked field potential responses

fEPSP

Field excitatory post-synaptic potential

GSK-3β

Glycogen synthase kinase-3β

HFS

High-frequency stimulation

I/O

Input/output

LTD

Long-term depression

LTP

Long-term potentiation

NMDA

N-methyl-d-aspartate

PPR

Paired-pulse ratio

TBS

Theta-burst stimulating

TTBS

Tween 20/tris-buffered saline

Notes

Acknowledgements

This research was supported by the Mid-career Researcher Program through a National Research Foundation of Korea (NRF) grant funded by the Ministry of Education, Science and Technology (MEST) (NRF-2015R1A2A2A01007838) and by the Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science and ICT (NRF-2017R1A5A2014768).

Compliance with Ethical Standards

Conflict of interest

The authors declare that there have no conflicts of interest.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Won Yong Jung
    • 1
    • 2
  • Haneul Kim
    • 3
  • Se Jin Jeon
    • 3
  • Hye Jin Park
    • 4
  • Hyuck Jai Choi
    • 2
  • Nam Jae Kim
    • 2
  • Dong Hyun Kim
    • 4
    • 5
  • Dae Sik Jang
    • 3
    Email author
  • Jong Hoon Ryu
    • 1
    • 3
    Email author
  1. 1.Department of Oriental Pharmaceutical Science, College of PharmacyKyung Hee UniversitySeoulRepublic of Korea
  2. 2.East-West Medical Research InstituteKyung Hee University Medical CenterSeoulRepublic of Korea
  3. 3.Department of Life and Nanopharmaceutical Sciences, College of PharmacyKyung Hee UniversitySeoulRepublic of Korea
  4. 4.Department of Medicinal Biotechnology, College of Health SciencesDong-A UniversityBusanRepublic of Korea
  5. 5.Institute of Convergence Bio-HealthDong-A UniversityBusanRepublic of Korea

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