Effects of gintonin-enriched fraction on hippocampal gene expressions

Background: Recently, gintonin and gintonin-enriched fraction (GEF) have been isolated from ginseng, a herbal medicine. Gintonin induces [Ca2+]i transition in cultured hippocampal neurons and stimulates acetylcholine release through LPA receptor activation. Oral administration of GEF is linked to hi...

Full description

Saved in:
Bibliographic Details
Main Authors: Rami Lee, Na-Eun Lee, Sun-Hye Choi, Sung Min Nam, Hyoung-Chun Kim, Hyewhon Rhim, Ik-Hyun Cho, Sung-Hee Hwang, Seung-Yeol Nah
Format: Article
Language:English
Published: Elsevier 2021-06-01
Series:Integrative Medicine Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2213422020301074
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850189032000061440
author Rami Lee
Na-Eun Lee
Sun-Hye Choi
Sung Min Nam
Hyoung-Chun Kim
Hyewhon Rhim
Ik-Hyun Cho
Sung-Hee Hwang
Seung-Yeol Nah
author_facet Rami Lee
Na-Eun Lee
Sun-Hye Choi
Sung Min Nam
Hyoung-Chun Kim
Hyewhon Rhim
Ik-Hyun Cho
Sung-Hee Hwang
Seung-Yeol Nah
author_sort Rami Lee
collection DOAJ
description Background: Recently, gintonin and gintonin-enriched fraction (GEF) have been isolated from ginseng, a herbal medicine. Gintonin induces [Ca2+]i transition in cultured hippocampal neurons and stimulates acetylcholine release through LPA receptor activation. Oral administration of GEF is linked to hippocampus-dependent cognitive enhancement and other neuroprotective effects; however, effects of its long-term administration on hippocampal gene expression remains unknown. Here, we used next-generation sequence (NGS) analysis to examine changes in hippocampal gene expressions after long-term oral administration of GEF. Methods: C57BL/6 mice were divided into three groups: control group, GEF50 (GEF 50 mg/kg, p.o.), and GEF100 (GEF 100 mg/kg, p.o.). After 22 days, total RNA was extracted from mouse hippocampal tissues. NGS was used for gene expression profiling; quantitative-real-time PCR and western blot were performed to quantify the changes in specific genes and to confirm the protein expression levels in treatment groups. Results: NGS analysis screened a total of 23,282 genes, analyzing 11-related categories. We focused on the neurogenesis category, which includes four genes for candidate markers: choline acetyltransferase (ChAT) gene, β3-adrenergic receptor (Adrb3) gene, and corticotrophin-releasing hormone (Crh) gene, and tryptophan 2,3-dioxygenase (Tdo2) gene. Real-time PCR showed a marked overexpression of ChAT, Adrb3, and Crh genes, while reduced expression of Tdo2. Western blot analysis also confirmed increased ChAT and decreased Tdo2 protein levels. Conclusion: We found that GEF affects mouse hippocampal gene expressions, associated with memory, cognitive, anti-stress and anti-anxiety functions, and neurodegeneration at differential degree, that might explain the genetic bases of GEF-mediated neuroprotective effects.
format Article
id doaj-art-0c8a95ffc09942aeb68c3bb5c04d18e6
institution OA Journals
issn 2213-4220
language English
publishDate 2021-06-01
publisher Elsevier
record_format Article
series Integrative Medicine Research
spelling doaj-art-0c8a95ffc09942aeb68c3bb5c04d18e62025-08-20T02:15:42ZengElsevierIntegrative Medicine Research2213-42202021-06-0110210047510.1016/j.imr.2020.100475Effects of gintonin-enriched fraction on hippocampal gene expressionsRami Lee0Na-Eun Lee1Sun-Hye Choi2Sung Min Nam3Hyoung-Chun Kim4Hyewhon Rhim5Ik-Hyun Cho6Sung-Hee Hwang7Seung-Yeol Nah8Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul, Republic of KoreaGinsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul, Republic of KoreaGinsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul, Republic of KoreaDepartment of Anatomy, School of Medicine and Institute for Environmental Science, Wonkwang University, Iksan, KoreaNeuro Psychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, Republic of KoreaCenter for Neuroscience, Korea Institute of Science and Technology, Seoul, Republic of KoreaDepartment of Convergence Medical Science, Department of Science in Korean Medicine and Brain Korea 21 Plus Program, Graduate School, Kyung Hee University, Seoul, Republic of KoreaDepartment of Pharmaceutical Engineering, College of Health Sciences, Sangji University, Wonju, Republic of KoreaGinsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea; Corresponding author at: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea.Background: Recently, gintonin and gintonin-enriched fraction (GEF) have been isolated from ginseng, a herbal medicine. Gintonin induces [Ca2+]i transition in cultured hippocampal neurons and stimulates acetylcholine release through LPA receptor activation. Oral administration of GEF is linked to hippocampus-dependent cognitive enhancement and other neuroprotective effects; however, effects of its long-term administration on hippocampal gene expression remains unknown. Here, we used next-generation sequence (NGS) analysis to examine changes in hippocampal gene expressions after long-term oral administration of GEF. Methods: C57BL/6 mice were divided into three groups: control group, GEF50 (GEF 50 mg/kg, p.o.), and GEF100 (GEF 100 mg/kg, p.o.). After 22 days, total RNA was extracted from mouse hippocampal tissues. NGS was used for gene expression profiling; quantitative-real-time PCR and western blot were performed to quantify the changes in specific genes and to confirm the protein expression levels in treatment groups. Results: NGS analysis screened a total of 23,282 genes, analyzing 11-related categories. We focused on the neurogenesis category, which includes four genes for candidate markers: choline acetyltransferase (ChAT) gene, β3-adrenergic receptor (Adrb3) gene, and corticotrophin-releasing hormone (Crh) gene, and tryptophan 2,3-dioxygenase (Tdo2) gene. Real-time PCR showed a marked overexpression of ChAT, Adrb3, and Crh genes, while reduced expression of Tdo2. Western blot analysis also confirmed increased ChAT and decreased Tdo2 protein levels. Conclusion: We found that GEF affects mouse hippocampal gene expressions, associated with memory, cognitive, anti-stress and anti-anxiety functions, and neurodegeneration at differential degree, that might explain the genetic bases of GEF-mediated neuroprotective effects.http://www.sciencedirect.com/science/article/pii/S2213422020301074GinsengGintoninHippocampus geneNGS analysisCognition
spellingShingle Rami Lee
Na-Eun Lee
Sun-Hye Choi
Sung Min Nam
Hyoung-Chun Kim
Hyewhon Rhim
Ik-Hyun Cho
Sung-Hee Hwang
Seung-Yeol Nah
Effects of gintonin-enriched fraction on hippocampal gene expressions
Integrative Medicine Research
Ginseng
Gintonin
Hippocampus gene
NGS analysis
Cognition
title Effects of gintonin-enriched fraction on hippocampal gene expressions
title_full Effects of gintonin-enriched fraction on hippocampal gene expressions
title_fullStr Effects of gintonin-enriched fraction on hippocampal gene expressions
title_full_unstemmed Effects of gintonin-enriched fraction on hippocampal gene expressions
title_short Effects of gintonin-enriched fraction on hippocampal gene expressions
title_sort effects of gintonin enriched fraction on hippocampal gene expressions
topic Ginseng
Gintonin
Hippocampus gene
NGS analysis
Cognition
url http://www.sciencedirect.com/science/article/pii/S2213422020301074
work_keys_str_mv AT ramilee effectsofgintoninenrichedfractiononhippocampalgeneexpressions
AT naeunlee effectsofgintoninenrichedfractiononhippocampalgeneexpressions
AT sunhyechoi effectsofgintoninenrichedfractiononhippocampalgeneexpressions
AT sungminnam effectsofgintoninenrichedfractiononhippocampalgeneexpressions
AT hyoungchunkim effectsofgintoninenrichedfractiononhippocampalgeneexpressions
AT hyewhonrhim effectsofgintoninenrichedfractiononhippocampalgeneexpressions
AT ikhyuncho effectsofgintoninenrichedfractiononhippocampalgeneexpressions
AT sungheehwang effectsofgintoninenrichedfractiononhippocampalgeneexpressions
AT seungyeolnah effectsofgintoninenrichedfractiononhippocampalgeneexpressions