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http://dx.doi.org/10.1016/j.jgr.2018.12.002

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

Kim, Dong Hoi (Convergence Research Center for Dementia, KIST)
Kim, Dae Won (Department of Biochemistry, College of Dentistry, Gangneung Wonju National University)
Jung, Bo Hyun (Department of Oral Anatomy, College of Dentistry, Gangneung Wonju National University)
Lee, Jong Hun (Department of Oral Anatomy, College of Dentistry, Gangneung Wonju National University)
Lee, Heesu (Department of Oral Anatomy, College of Dentistry, Gangneung Wonju National University)
Hwang, Gwi Seo (College of Korean Medicine, Gacheun University)
Kang, Ki Sung (College of Korean Medicine, Gacheun University)
Lee, Jae Wook (Convergence Research Center for Dementia, KIST)
Publication Information
Journal of Ginseng Research / v.43, no.2, 2019 , pp. 326-334 More about this Journal
Abstract
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 $Ca^{2+}$ 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 ($25.7{\mu}M$). Cellular $Ca^{2+}$ 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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