Gintonin facilitates brain delivery of donepezil, a therapeutic drug for Alzheimer disease, through lysophosphatidic acid 1/3 and vascular endothelial growth factor receptors
Open accessAbstract
BACKGROUND: 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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Gintonin can reduce Alzheimer's disease symptoms and progression through autophagy stimulation, neurogenesis, decreasing oxidative stress, and anti-inflammatory activities.
“Additionally, gintonin can reduce AD symptoms and progression through autophagy stimulation, neurogenesis, decreasing oxidative stress, and anti-inflammatory activities [72].”
From Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights (2023) · cites this paper as [72]
Gintonin could improve the brain delivery of donepezil.
“They also showed that gintonin could improve the brain delivery of donepezil, a representative cognition-improving drug used in AD clinics [72].”
From Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights (2023) · cites this paper as [72]
Systemic treatment with gintonin enhances paracellular permeability of the blood-brain barrier through the LPA1/3 receptor.
“Recently, Choi et al. demonstrated that systemic treatment with gintonin enhances paracellular permeability of the blood-brain barrier through the LPA1/3 receptor.”
From Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights (2023) · cites this paper as [72]
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- Authors
- Choi, S.-H., Lee, N.-E., Cho, H.-J., Lee, R. M., Rhim, H., Kim, H.-C., Han, M., Lee, E.-H., Park, J., Kim, J. N., Kim, B. J., & Nah, S.-Y.
- Affiliations
- Konkuk University (KR)
- Korea Institute of Science and Technology (KR)
- Kangwon National University (KR)
- Daegu-Gyeongbuk Medical Innovation Foundation (KR)
- Pusan National University (KR)
- Corresponding author
- Kim, Byung Joo
- Nah, Seung-Yeol
- ORCID
- Venue
- Journal of Ginseng Research
- Publisher
- Elsevier BV
- Published
- 2021-03
- Volume
- 45
- Issue
- 2
- Pages
- 264-272
- ISSN
- 1226-8453 (ISSN-L)
- PMC
- PMC8020287
- OpenAlex
- W2995652302
- Cited by
- 20
- References
- 22
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 2
- FWCI
- 0.55
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- Journal of Ginseng Research (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- NRF)
- Ministry of Science, Information & Communication Technology (ICT), and Future Planning (NRF-2016M3C7A1913845, NRF-2016M3C7A1913933)
- Basic Science Research (NRF-2017R1D1A1A09000520)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- gintonin, donepezil, Alzheimer's disease, brain drug delivery, vascular endothelial growth factor receptor, blood-brain barrier permeability, cerebrospinal fluid, Ki16425, mannitol, intravenous administration
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