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Mol Cells. 2015 Sep;38(9):796-805. doi: 10.14348/molcells.2015.0116. Epub 2015 Aug 7.

Oral Administration of Gintonin Attenuates Cholinergic Impairments by Scopolamine, Amyloid-β Protein, and Mouse Model of Alzheimer's Disease.

Author information

1
Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Korea.
2
Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Korea.
3
Department of Convergence Medical Science, Brain Korea 21 Plus Program, and Institute of Oriental Medicine, College of Oriental Korean Medicine, Kyung Hee University, Seoul 130-701, Korea.
4
Department of Pharmaceutical Engineering, Sangji University, Wonju 220-702, Korea.
5
Department of Biological Sciences, Konkuk University, Seoul 143-701, Korea.
6
Department of Pharmacology, College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea.
7
Center for Neuroscience, Korea Institute of Science and Technology Seoul 139-791, Korea.

Abstract

Gintonin is a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand. Oral administration of gintonin ameliorates learning and memory dysfunctions in Alzheimer's disease (AD) animal models. The brain cholinergic system plays a key role in cognitive functions. The brains of AD patients show a reduction in acetylcholine concentration caused by cholinergic system impairments. However, little is known about the role of LPA in the cholinergic system. In this study, we used gintonin to investigate the effect of LPA receptor activation on the cholinergic system in vitro and in vivo using wild-type and AD animal models. Gintonin induced [Ca(2+)]i transient in cultured mouse hippocampal neural progenitor cells (NPCs). Gintonin-mediated [Ca(2+)]i transients were linked to stimulation of acetylcholine release through LPA receptor activation. Oral administration of gintonin-enriched fraction (25, 50, or 100 mg/kg, 3 weeks) significantly attenuated scopolamine-induced memory impairment. Oral administration of gintonin (25 or 50 mg/kg, 2 weeks) also significantly attenuated amyloid-β protein (Aβ)-induced cholinergic dysfunctions, such as decreased acetylcholine concentration, decreased choline acetyltransferase (ChAT) activity and immunoreactivity, and increased acetylcholine esterase (AChE) activity. In a transgenic AD mouse model, long-term oral administration of gintonin (25 or 50 mg/kg, 3 months) also attenuated AD-related cholinergic impairments. In this study, we showed that activation of G protein-coupled LPA receptors by gintonin is coupled to the regulation of cholinergic functions. Furthermore, this study showed that gintonin could be a novel agent for the restoration of cholinergic system damages due to Aβ and could be utilized for AD prevention or therapy.

KEYWORDS:

LPA receptors; acetylcholine; cholinergic systems; ginseng; gintonin

PMID:
26255830
PMCID:
PMC4588723
DOI:
10.14348/molcells.2015.0116
[Indexed for MEDLINE]
Free PMC Article

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