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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2021.3
- 수록면
- 264 - 272 (9page)
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초록· 키워드
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Background: Gintonin is a ginseng-derived exogenous G-protein―coupled lysophosphatidic acid (LPA) receptor ligand, which exhibits in vitro and in vivo functions against Alzheimer disease (AD) through lysophosphatidic acid 1/3 receptors. A recent study demonstrated that systemic treatment with gintonin enhances paracellular permeability of the blood―brain barrier (BBB) through the LPA1/3 receptor. However, little is known about whether gintonin can enhance brain delivery of donepezil (DPZ) (Aricept), which is a representative cognition-improving drug used in AD clinics. In the present study, we examined whether systemic administration of gintonin can stimulate brain delivery of DPZ.
Methods: We administered gintonin and DPZ alone or coadministered gintonin with DPZ intravenously or orally to rats. Then we collected the cerebral spinal fluid (CSF) and serum and determined the DPZ concentration through liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis.
Results: Intravenous, but not oral, coadministration of gintonin with DPZ increased the CSF concentration of DPZ in a concentration- and time-dependent manner. Gintonin-mediated enhancement of brain delivery of DPZ was blocked by Ki16425, a LPA1/3 receptor antagonist. Coadministration of vascular endothelial growth factor (VEGF) þ gintonin with DPZ similarly increased CSF DPZ concentration. However, gintonin-mediated enhancement of brain delivery of DPZ was blocked by axitinip, a VEGF receptor antagonist. Mannitol, a BBB disrupting agent that increases the BBB permeability, enhanced gintonin-mediated enhancement of brain delivery of DPZ.
Conclusions: We found that intravenous, but not oral, coadministration of gintonin facilitates brain delivery of DPZ from plasma via LPA1/3 and VEGF receptors. Gintonin is a potential candidate as a ginseng-derived novel agent for the brain delivery of DPZ for treatment of patients with AD.
Methods: We administered gintonin and DPZ alone or coadministered gintonin with DPZ intravenously or orally to rats. Then we collected the cerebral spinal fluid (CSF) and serum and determined the DPZ concentration through liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis.
Results: Intravenous, but not oral, coadministration of gintonin with DPZ increased the CSF concentration of DPZ in a concentration- and time-dependent manner. Gintonin-mediated enhancement of brain delivery of DPZ was blocked by Ki16425, a LPA1/3 receptor antagonist. Coadministration of vascular endothelial growth factor (VEGF) þ gintonin with DPZ similarly increased CSF DPZ concentration. However, gintonin-mediated enhancement of brain delivery of DPZ was blocked by axitinip, a VEGF receptor antagonist. Mannitol, a BBB disrupting agent that increases the BBB permeability, enhanced gintonin-mediated enhancement of brain delivery of DPZ.
Conclusions: We found that intravenous, but not oral, coadministration of gintonin facilitates brain delivery of DPZ from plasma via LPA1/3 and VEGF receptors. Gintonin is a potential candidate as a ginseng-derived novel agent for the brain delivery of DPZ for treatment of patients with AD.
목차
ABSTRACT
1. Introduction
2. Materials and methods
3. Results
4. Discussion
References
참고문헌 (22)
참고문헌 신청
Meng G / 2016 / A systematic investigation into aging related genes in brain and their relationship with Alzheimer's disease / PLoS One 11:e0150624
Peters R / 2006 / Ageing and the brain / Postgrad Med J 82:84~88
Colovic MB / 2013 / Acetylcholinesterase inhibitors : pharmacology and toxicology / Curr Neuropharmacol 11:315~335
Burns A / 1999 / The effects of donepezil in Alzheimer’s disease e results from a multinational trial / Dement Geriatr Cogn Disord 10:237~244
Jelic V / 2010 / Donepezil : a review of pharmacological characteristics and role in the management of Alzheimer disease / Clin Med Insights Ther 2:771~788
Peters R / 2006 / Ageing and the brain / Postgrad Med J 82:84~88
Colovic MB / 2013 / Acetylcholinesterase inhibitors : pharmacology and toxicology / Curr Neuropharmacol 11:315~335
Burns A / 1999 / The effects of donepezil in Alzheimer’s disease e results from a multinational trial / Dement Geriatr Cogn Disord 10:237~244
Jelic V / 2010 / Donepezil : a review of pharmacological characteristics and role in the management of Alzheimer disease / Clin Med Insights Ther 2:771~788
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