Gintonin Binds to Reduced LPA4 Receptor Subtype in Human Cortical Neurons in Alzheimer’s Disease Brains

Ginseng, a traditional herbal medicine with a long history of use, is known to support human health, particularly by influencing brain function. Recent studies have identified gintonin, a lysophosphatidic acid (LPA) receptor ligand derived from ginseng, as a key bioactive. However, the specific LPA...

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Main Authors: Kyu-Sung Kim, Rami Lee, Inyeong Park, Sung-Hee Hwang, Yeshin Kim, Jae-Won Jang, Hyung-Seok Kim, Seong-Min Choi, Sang Jin Kim, Hwa Jin Cho, Ik-Hyun Cho, Jong-Hoon Kim, Do-Geun Kim, Seung-Yeol Nah
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/15/2/179
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author Kyu-Sung Kim
Rami Lee
Inyeong Park
Sung-Hee Hwang
Yeshin Kim
Jae-Won Jang
Hyung-Seok Kim
Seong-Min Choi
Sang Jin Kim
Hwa Jin Cho
Ik-Hyun Cho
Jong-Hoon Kim
Do-Geun Kim
Seung-Yeol Nah
author_facet Kyu-Sung Kim
Rami Lee
Inyeong Park
Sung-Hee Hwang
Yeshin Kim
Jae-Won Jang
Hyung-Seok Kim
Seong-Min Choi
Sang Jin Kim
Hwa Jin Cho
Ik-Hyun Cho
Jong-Hoon Kim
Do-Geun Kim
Seung-Yeol Nah
author_sort Kyu-Sung Kim
collection DOAJ
description Ginseng, a traditional herbal medicine with a long history of use, is known to support human health, particularly by influencing brain function. Recent studies have identified gintonin, a lysophosphatidic acid (LPA) receptor ligand derived from ginseng, as a key bioactive. However, the specific LPA receptor subtypes targeted by gintonin in the human brain to exert its anti-Alzheimer’s (AD) effects remain unclear. This study aimed to elucidate the LPA receptor subtype targeted by gintonin in the human cortex. Using a fluorescent gintonin conjugate, we investigated receptor binding in cortical samples from healthy individuals (<i>n</i> = 4) and AD patients (<i>n</i> = 4). Our results demonstrated that fluorescent gintonin selectively binds to human cortical neurons rather than glial cells and that gintonin-binding sites are co-localized with the LPA4 receptor subtype. Furthermore, the expression of LPA4 receptors was significantly reduced in the cortical neurons of AD patients. These results suggest that the LPA4 receptor may serve as a novel histopathological marker for AD and represent a promising therapeutic target for gintonin-based prevention and treatment strategies.
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series Biomolecules
spelling doaj-art-9072aba48a6f4fcbb4c33d7b49ef5ba12025-08-20T02:44:59ZengMDPI AGBiomolecules2218-273X2025-01-0115217910.3390/biom15020179Gintonin Binds to Reduced LPA4 Receptor Subtype in Human Cortical Neurons in Alzheimer’s Disease BrainsKyu-Sung Kim0Rami Lee1Inyeong Park2Sung-Hee Hwang3Yeshin Kim4Jae-Won Jang5Hyung-Seok Kim6Seong-Min Choi7Sang Jin Kim8Hwa Jin Cho9Ik-Hyun Cho10Jong-Hoon Kim11Do-Geun Kim12Seung-Yeol Nah13Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of KoreaGinsentology Research Laboratory, Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of KoreaNeuroimmunology Laboratory, Dementia Research Group, Korea Brain Research Institute, Daegu 41062, Republic of KoreaDepartment of Pharmaceutical Engineering, College of Health Sciences, Sangji University, Wonju 26339, Republic of KoreaDepartment of Neurology, Kangwon National University Hospital, Chuncheon 24289, Republic of KoreaDepartment of Neurology, Kangwon National University Hospital, Chuncheon 24289, Republic of KoreaDepartment of Neurosurgery, Chonnam National University Medical School, Research Institute of Medical Sciences, Gwangju 61469, Republic of KoreaDepartment of Neurology, Chonnam National University Medical School, Jebong-ro, Gwangju 61469, Republic of KoreaDepartment of Neurology, Busan Paik Hospital, Inje University College of Medicine, Busan 47392, Republic of KoreaBusan & Gyeongnam Reference Laboratory, Department of Pathology, Seegene Medical Foundation, Busan 48792, Republic of KoreaDepartment of Convergence Medical Science, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaCollege of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, Iksan-City 54596, Republic of KoreaNeuroimmunology Laboratory, Dementia Research Group, Korea Brain Research Institute, Daegu 41062, Republic of KoreaGinsentology Research Laboratory, Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of KoreaGinseng, a traditional herbal medicine with a long history of use, is known to support human health, particularly by influencing brain function. Recent studies have identified gintonin, a lysophosphatidic acid (LPA) receptor ligand derived from ginseng, as a key bioactive. However, the specific LPA receptor subtypes targeted by gintonin in the human brain to exert its anti-Alzheimer’s (AD) effects remain unclear. This study aimed to elucidate the LPA receptor subtype targeted by gintonin in the human cortex. Using a fluorescent gintonin conjugate, we investigated receptor binding in cortical samples from healthy individuals (<i>n</i> = 4) and AD patients (<i>n</i> = 4). Our results demonstrated that fluorescent gintonin selectively binds to human cortical neurons rather than glial cells and that gintonin-binding sites are co-localized with the LPA4 receptor subtype. Furthermore, the expression of LPA4 receptors was significantly reduced in the cortical neurons of AD patients. These results suggest that the LPA4 receptor may serve as a novel histopathological marker for AD and represent a promising therapeutic target for gintonin-based prevention and treatment strategies.https://www.mdpi.com/2218-273X/15/2/179ginsenggintoninLPA4 receptorhuman cortexAD prevention
spellingShingle Kyu-Sung Kim
Rami Lee
Inyeong Park
Sung-Hee Hwang
Yeshin Kim
Jae-Won Jang
Hyung-Seok Kim
Seong-Min Choi
Sang Jin Kim
Hwa Jin Cho
Ik-Hyun Cho
Jong-Hoon Kim
Do-Geun Kim
Seung-Yeol Nah
Gintonin Binds to Reduced LPA4 Receptor Subtype in Human Cortical Neurons in Alzheimer’s Disease Brains
Biomolecules
ginseng
gintonin
LPA4 receptor
human cortex
AD prevention
title Gintonin Binds to Reduced LPA4 Receptor Subtype in Human Cortical Neurons in Alzheimer’s Disease Brains
title_full Gintonin Binds to Reduced LPA4 Receptor Subtype in Human Cortical Neurons in Alzheimer’s Disease Brains
title_fullStr Gintonin Binds to Reduced LPA4 Receptor Subtype in Human Cortical Neurons in Alzheimer’s Disease Brains
title_full_unstemmed Gintonin Binds to Reduced LPA4 Receptor Subtype in Human Cortical Neurons in Alzheimer’s Disease Brains
title_short Gintonin Binds to Reduced LPA4 Receptor Subtype in Human Cortical Neurons in Alzheimer’s Disease Brains
title_sort gintonin binds to reduced lpa4 receptor subtype in human cortical neurons in alzheimer s disease brains
topic ginseng
gintonin
LPA4 receptor
human cortex
AD prevention
url https://www.mdpi.com/2218-273X/15/2/179
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