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Gintonin Mitigates MPTP-Induced Loss of Nigrostriatal Dopaminergic Neurons and Accumulation of α-Synuclein via the Nrf2/HO-1 Pathway.
Mol Neurobiol. 2019 Jan; 56(1):39-55.MN

Abstract

Gintonin, a ginseng-derived glycolipoprotein isolated from ginseng, has been shown to be neuroprotective in several neurological disorders such as Alzheimer's disease models and depressive-like behaviors. In this study, we sought to investigate the potential protective mechanisms of gintonin in an in vivo MPTP and in vitro MPP+-mediated Parkinson's disease (PD) model. We hypothesized that activation of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1, potential therapeutic targets for neurodegeneration) with gintonin could abrogate PD-associated neurotoxicity by modulating the accumulation of α-synuclein, neuroinflammation, and apoptotic cell death in an MPTP/MPP+ models of PD. Our in vivo and in vitro findings suggest that the neuroprotective effects of gintonin were associated with the regulation of the Nrf2/HO-1 pathway, which regulated the expression of proinflammatory cytokines and nitric oxide synthase and apoptotic markers in the substantia nigra and striatum of the mice. Moreover, the neuroprotective effects of gintonin were also associated with a reduction in α-synuclein accumulation in the mouse substantia nigra and striatum. The neuroprotective effects of gintonin were further validated by analyzing the effects of gintonin on MPP+-treated SH-SY5Y cells, which confirmed the protective effects of gintonin. It remains for future basic and clinical research to determine the potential use of gintonin in Parkinson's disease. However, to the best of our knowledge, marked alterations in biochemical and morphological setup of midbrain dopaminergic pathways by gintonin in MPTP mice model have not been previously reported. We believe that gintonin might be explored as an important therapeutic agent in the treatment of PD.

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Authors+Show Affiliations

Jo MG
Division of Life Science and Applied Life Science (BK21 plus), College of Natural Sciences, Gyeongsang National University, Jinju, 52802, Republic of Korea.
Ikram M
Division of Life Science and Applied Life Science (BK21 plus), College of Natural Sciences, Gyeongsang National University, Jinju, 52802, Republic of Korea.
Jo MH
Division of Life Science and Applied Life Science (BK21 plus), College of Natural Sciences, Gyeongsang National University, Jinju, 52802, Republic of Korea.
Yoo L
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea.
Chung KC
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea.
Nah SY
Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul, 05029, Republic of Korea.
Hwang H
Center for Neuroscience, Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.
Rhim H
Center for Neuroscience, Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea. hrhim@kist.re.kr.
Kim MO
Division of Life Science and Applied Life Science (BK21 plus), College of Natural Sciences, Gyeongsang National University, Jinju, 52802, Republic of Korea. mokim@gnu.ac.kr. Division of Life Science and Applied Life Science, College of Natural Sciences, Gyeongsang National University, Jinju, 660-701, Republic of Korea. mokim@gnu.ac.kr.

MeSH

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineAnimalsApoptosisBiomarkersCell Line, TumorCorpus StriatumDisease Models, AnimalDopaminergic NeuronsGlial Fibrillary Acidic ProteinGliosisHeme Oxygenase-1HumansInflammation MediatorsMaleMice, Inbred C57BLMotor ActivityNF-E2-Related Factor 2Neuroprotective AgentsNeurotoxinsOxidative StressParkinson DiseasePlant ExtractsRotenoneSignal TransductionSubstantia NigraTyrosine 3-MonooxygenaseUp-Regulationalpha-Synuclein

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29675576

Citation

Jo, Min Gi, et al. "Gintonin Mitigates MPTP-Induced Loss of Nigrostriatal Dopaminergic Neurons and Accumulation of α-Synuclein Via the Nrf2/HO-1 Pathway." Molecular Neurobiology, vol. 56, no. 1, 2019, pp. 39-55.
Jo MG, Ikram M, Jo MH, et al. Gintonin Mitigates MPTP-Induced Loss of Nigrostriatal Dopaminergic Neurons and Accumulation of α-Synuclein via the Nrf2/HO-1 Pathway. Mol Neurobiol. 2019;56(1):39-55.
Jo, M. G., Ikram, M., Jo, M. H., Yoo, L., Chung, K. C., Nah, S. Y., Hwang, H., Rhim, H., & Kim, M. O. (2019). Gintonin Mitigates MPTP-Induced Loss of Nigrostriatal Dopaminergic Neurons and Accumulation of α-Synuclein via the Nrf2/HO-1 Pathway. Molecular Neurobiology, 56(1), 39-55. https://doi.org/10.1007/s12035-018-1020-1
Jo MG, et al. Gintonin Mitigates MPTP-Induced Loss of Nigrostriatal Dopaminergic Neurons and Accumulation of α-Synuclein Via the Nrf2/HO-1 Pathway. Mol Neurobiol. 2019;56(1):39-55. PubMed PMID: 29675576.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gintonin Mitigates MPTP-Induced Loss of Nigrostriatal Dopaminergic Neurons and Accumulation of α-Synuclein via the Nrf2/HO-1 Pathway. AU - Jo,Min Gi, AU - Ikram,Muhammad, AU - Jo,Myeung Hoon, AU - Yoo,Lang, AU - Chung,Kwang Chul, AU - Nah,Seung-Yeol, AU - Hwang,Hongik, AU - Rhim,Hyewhon, AU - Kim,Myeong Ok, Y1 - 2018/04/19/ PY - 2018/01/18/received PY - 2018/03/16/accepted PY - 2018/4/21/pubmed PY - 2019/4/2/medline PY - 2018/4/21/entrez KW - Gintonin KW - MPTP KW - Neuroinflammation KW - Neuroprotection KW - Nrf2/HO-1 pathway KW - Parkinson’s disease SP - 39 EP - 55 JF - Molecular neurobiology JO - Mol Neurobiol VL - 56 IS - 1 N2 - Gintonin, a ginseng-derived glycolipoprotein isolated from ginseng, has been shown to be neuroprotective in several neurological disorders such as Alzheimer's disease models and depressive-like behaviors. In this study, we sought to investigate the potential protective mechanisms of gintonin in an in vivo MPTP and in vitro MPP+-mediated Parkinson's disease (PD) model. We hypothesized that activation of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1, potential therapeutic targets for neurodegeneration) with gintonin could abrogate PD-associated neurotoxicity by modulating the accumulation of α-synuclein, neuroinflammation, and apoptotic cell death in an MPTP/MPP+ models of PD. Our in vivo and in vitro findings suggest that the neuroprotective effects of gintonin were associated with the regulation of the Nrf2/HO-1 pathway, which regulated the expression of proinflammatory cytokines and nitric oxide synthase and apoptotic markers in the substantia nigra and striatum of the mice. Moreover, the neuroprotective effects of gintonin were also associated with a reduction in α-synuclein accumulation in the mouse substantia nigra and striatum. The neuroprotective effects of gintonin were further validated by analyzing the effects of gintonin on MPP+-treated SH-SY5Y cells, which confirmed the protective effects of gintonin. It remains for future basic and clinical research to determine the potential use of gintonin in Parkinson's disease. However, to the best of our knowledge, marked alterations in biochemical and morphological setup of midbrain dopaminergic pathways by gintonin in MPTP mice model have not been previously reported. We believe that gintonin might be explored as an important therapeutic agent in the treatment of PD. SN - 1559-1182 UR - https://www.unboundmedicine.com/medline/citation/29675576/Gintonin_Mitigates_MPTP_Induced_Loss_of_Nigrostriatal_Dopaminergic_Neurons_and_Accumulation_of_α_Synuclein_via_the_Nrf2/HO_1_Pathway_ DB - PRIME DP - Unbound Medicine ER -