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Gintonin facilitates brain delivery of donepezil, a therapeutic drug for Alzheimer disease, through lysophosphatidic acid 1/3 and vascular endothelial growth factor receptors.
Choi, Sun-Hye; Lee, Na-Eun; Cho, Hee-Jung; Lee, Ra Mi; Rhim, Hyewhon; Kim, Hyoung-Chun; Han, Mun; Lee, Eun-Hee; Park, Juyoung; Nah, Seung-Yeol.
Afiliação
  • Choi SH; Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul, 05029, South Korea.
  • Lee NE; Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul, 05029, South Korea.
  • Cho HJ; Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul, 05029, South Korea.
  • Lee RM; Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul, 05029, South Korea.
  • Rhim H; Center for Neuroscience, Korea Institute of Science and Technology, Seoul, 02792, South Korea.
  • Kim HC; Neuropsychopharmacology and Toxicology program, College of Pharmacy, Kangwon National University, Chuncheon, 24341, South Korea.
  • Han M; Medical Device Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, 41061, South Korea.
  • Lee EH; Medical Device Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, 41061, South Korea.
  • Park J; Medical Device Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, 41061, South Korea.
  • Nah SY; Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul, 05029, South Korea.
J Ginseng Res ; 45(2): 264-272, 2021 Mar.
Article em En | MEDLINE | ID: mdl-33841007
ABSTRACT

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) + 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.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2021 Tipo de documento: Article