Ginsenoside Rb2 suppresses the glutamate-mediated oxidative stress and neuronal cell death in HT22 cells

Background: The objective of our study was to analyze the neuroprotective effects of ginsenoside derivatives Rb1, Rb2, Rc, Rd, Rg1, and Rg3 against glutamate-mediated neurotoxicity in HT22 hippocampal mouse neuron cells. Methods: The neuroprotective effect of ginsenosides were evaluated by measuring...

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Main Authors: Dong Hoi Kim, Dae Won Kim, Bo Hyun Jung, Jong Hun Lee, Heesu Lee, Gwi Seo Hwang, Ki Sung Kang, Jae Wook Lee
Format: Article
Language:English
Published: Elsevier 2019-04-01
Series:Journal of Ginseng Research
Online Access:http://www.sciencedirect.com/science/article/pii/S1226845318302343
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author Dong Hoi Kim
Dae Won Kim
Bo Hyun Jung
Jong Hun Lee
Heesu Lee
Gwi Seo Hwang
Ki Sung Kang
Jae Wook Lee
author_facet Dong Hoi Kim
Dae Won Kim
Bo Hyun Jung
Jong Hun Lee
Heesu Lee
Gwi Seo Hwang
Ki Sung Kang
Jae Wook Lee
author_sort Dong Hoi Kim
collection DOAJ
description Background: The objective of our study was to analyze the neuroprotective effects of ginsenoside derivatives Rb1, Rb2, Rc, Rd, Rg1, and Rg3 against glutamate-mediated neurotoxicity in HT22 hippocampal mouse neuron cells. Methods: The neuroprotective effect of ginsenosides were evaluated by measuring cell viability. Protein expressions of mitogen-activated protein kinase (MAPK), Bcl2, Bax, and apoptosis-inducing factor (AIF) were determined by Western blot analysis. The occurrence of apoptotic and death cells was determined by flow cytometry. Cellular level of Ca2+ and reactive oxygen species (ROS) levels were evaluated by image analysis using the fluorescent probes Fluor-3 and 2′,7′-dichlorodihydrofluorescein diacetate, respectively. In vivo efficacy of neuroprotection was evaluated using the Mongolian gerbil of ischemic brain injury model. Result: Reduction of cell viability by glutamate (5 mM) was significantly suppressed by treatment with ginsenoside Rb2. Phosphorylation of MAPKs, Bax, and nuclear AIF was gradually increased by treatment with 5 mM of glutamate and decreased by co-treatment with Rb2. The occurrence of apoptotic cells was decreased by treatment with Rb2 (25.7 μM). Cellular Ca2+ and ROS levels were decreased in the presence of Rb2, and in vivo data indicated that Rb2 treatment (10 mg/kg) significantly diminished the number of degenerated neurons. Conclusion: Our results suggest that Rb2 possesses neuroprotective properties that suppress glutamate-induced neurotoxicity. The molecular mechanism of Rb2 is by suppressing the MAPKs activity and AIF translocation. Keywords: Ginsenoside Rb2, Neurotoxicity, MAPK, Reactive oxygen species
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spelling doaj.art-a42688d071224ff68ea6a85cc4f3dff42022-12-22T01:03:53ZengElsevierJournal of Ginseng Research1226-84532019-04-01432326334Ginsenoside Rb2 suppresses the glutamate-mediated oxidative stress and neuronal cell death in HT22 cellsDong Hoi Kim0Dae Won Kim1Bo Hyun Jung2Jong Hun Lee3Heesu Lee4Gwi Seo Hwang5Ki Sung Kang6Jae Wook Lee7Convergence Research Center for Dementia, KIST, Seoul, Republic of KoreaDepartment of Biochemistry, College of Dentistry, Gangneung Wonju National University, Gangneung, Republic of KoreaDepartment of Oral Anatomy, College of Dentistry, Gangneung Wonju National University, Gangneung, Republic of KoreaDepartment of Oral Anatomy, College of Dentistry, Gangneung Wonju National University, Gangneung, Republic of KoreaDepartment of Oral Anatomy, College of Dentistry, Gangneung Wonju National University, Gangneung, Republic of KoreaCollege of Korean Medicine, Gacheun University, Seongnam, Republic of KoreaCollege of Korean Medicine, Gacheun University, Seongnam, Republic of Korea; Corresponding author. College of Korean Medicine, Gacheun University, Seongnam, Republic of Korea.Convergence Research Center for Dementia, KIST, Seoul, Republic of Korea; Natural Constituent Research Center, KIST, Gangneung, Republic of Korea; Corresponding author. Convergence Research Center for Dementia, KIST, Seoul, Republic of Korea.Background: The objective of our study was to analyze the neuroprotective effects of ginsenoside derivatives Rb1, Rb2, Rc, Rd, Rg1, and Rg3 against glutamate-mediated neurotoxicity in HT22 hippocampal mouse neuron cells. Methods: The neuroprotective effect of ginsenosides were evaluated by measuring cell viability. Protein expressions of mitogen-activated protein kinase (MAPK), Bcl2, Bax, and apoptosis-inducing factor (AIF) were determined by Western blot analysis. The occurrence of apoptotic and death cells was determined by flow cytometry. Cellular level of Ca2+ and reactive oxygen species (ROS) levels were evaluated by image analysis using the fluorescent probes Fluor-3 and 2′,7′-dichlorodihydrofluorescein diacetate, respectively. In vivo efficacy of neuroprotection was evaluated using the Mongolian gerbil of ischemic brain injury model. Result: Reduction of cell viability by glutamate (5 mM) was significantly suppressed by treatment with ginsenoside Rb2. Phosphorylation of MAPKs, Bax, and nuclear AIF was gradually increased by treatment with 5 mM of glutamate and decreased by co-treatment with Rb2. The occurrence of apoptotic cells was decreased by treatment with Rb2 (25.7 μM). Cellular Ca2+ and ROS levels were decreased in the presence of Rb2, and in vivo data indicated that Rb2 treatment (10 mg/kg) significantly diminished the number of degenerated neurons. Conclusion: Our results suggest that Rb2 possesses neuroprotective properties that suppress glutamate-induced neurotoxicity. The molecular mechanism of Rb2 is by suppressing the MAPKs activity and AIF translocation. Keywords: Ginsenoside Rb2, Neurotoxicity, MAPK, Reactive oxygen specieshttp://www.sciencedirect.com/science/article/pii/S1226845318302343
spellingShingle Dong Hoi Kim
Dae Won Kim
Bo Hyun Jung
Jong Hun Lee
Heesu Lee
Gwi Seo Hwang
Ki Sung Kang
Jae Wook Lee
Ginsenoside Rb2 suppresses the glutamate-mediated oxidative stress and neuronal cell death in HT22 cells
Journal of Ginseng Research
title Ginsenoside Rb2 suppresses the glutamate-mediated oxidative stress and neuronal cell death in HT22 cells
title_full Ginsenoside Rb2 suppresses the glutamate-mediated oxidative stress and neuronal cell death in HT22 cells
title_fullStr Ginsenoside Rb2 suppresses the glutamate-mediated oxidative stress and neuronal cell death in HT22 cells
title_full_unstemmed Ginsenoside Rb2 suppresses the glutamate-mediated oxidative stress and neuronal cell death in HT22 cells
title_short Ginsenoside Rb2 suppresses the glutamate-mediated oxidative stress and neuronal cell death in HT22 cells
title_sort ginsenoside rb2 suppresses the glutamate mediated oxidative stress and neuronal cell death in ht22 cells
url http://www.sciencedirect.com/science/article/pii/S1226845318302343
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