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

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.

• Authors: Hyeon-Joong Kim, Eun-Joo Shin, Byung-Hwan Lee, Sun-Hye Choi, Seok-Won Jung, Ik-Hyun Cho, Sung-Hee Hwang, Joon Yong Kim, Jung-Soo Han, ChiHye Chung, Choon-Gon Jang, Hyewon Rhim, Hyoung-Chun Kim, Seung-Yeol Nah
• Journal: Molecules and cells (Mol Cells) Vol. 38 Issue 9 Pg. 796-805 (Sep 2015) ISSN: 0219-1032 [Electronic] United States
• PMID: 26255830 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Peptide Fragments
• Plant Extracts
• amyloid beta-protein (1-40)
• gintonin
• Scopolamine
• Choline O-Acetyltransferase
• Acetylcholine

Topics

• Acetylcholine (metabolism)
• Administration, Oral
• Alzheimer Disease (drug therapy, metabolism)
• Amyloid beta-Peptides (metabolism)
• Animals
• Calcium Signaling
• Cells, Cultured
• Choline O-Acetyltransferase (metabolism)
• Cholinergic Neurons (drug effects, physiology)
• Disease Models, Animal
• Hippocampus (drug effects, enzymology, pathology)
• Male
• Memory Disorders (chemically induced, drug therapy)
• Mice, Inbred C57BL
• Mice, Inbred ICR
• Mice, Transgenic
• Neural Stem Cells (drug effects, physiology)
• Peptide Fragments (metabolism)
• Plant Extracts (administration & dosage)
• Scopolamine