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RETRACTED ARTICLE: Gintonin Mitigates MPTP-Induced Loss of Nigrostriatal Dopaminergic Neurons and Accumulation of α-Synuclein via the Nrf2/HO-1 Pathway

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This article was retracted on 16 April 2024

This article has been updated

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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Abbreviations

DA:

Dopamine

DMSO:

Dimethyl sulfoxide

FBS:

Fetal bovine serum

HO-1:

Heme oxygenase-1

NOS-2:

Nitric oxide synthase-2

MPP+ :

1-Methyl-4-phenylpyridinium

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Nrf2:

Nuclear factor erythroid 2-related factor 2

PD:

Parkinson’s disease

ROS:

Reactive oxygen species

SNpc:

Substantia nigra pars compacta

STR:

Striatum

TH:

Tyrosine hydroxylase

TNF-α:

Tumor necrosis factor-α

COX-2:

Cyclo-oxygenase-2

LPO:

Lipid peroxidation

Gt:

Gintonin

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Acknowledgments

This research was supported by the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2016M3C7A1904391 and NRF-2016M3C7A1913845).

Author information

Author notes

  1. Min Gi Jo, Muhammad Ikram and Myeung Hoon Jo contributed equally to this work.

Authors and Affiliations

  1. Division of Life Science and Applied Life Science (BK21 plus), College of Natural Sciences, Gyeongsang National University, Jinju, 52802, Republic of Korea

    Min Gi Jo, Muhammad Ikram, Myeung Hoon Jo & Myeong Ok Kim

  2. Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea

    Lang Yoo & Kwang Chul Chung

  3. Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul, 05029, Republic of Korea

    Seung-Yeol Nah

  4. 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

    Hongik Hwang & Hyewhon Rhim

  5. Division of Life Science and Applied Life Science, College of Natural Sciences, Gyeongsang National University, Jinju, 660-701, Republic of Korea

    Myeong Ok Kim

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  4. Lang Yoo
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  5. Kwang Chul Chung
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  6. Seung-Yeol Nah
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  7. Hongik Hwang
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  8. Hyewhon Rhim
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  9. Myeong Ok Kim
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Contributions

MGJ: Concept design, data collection and assembly, data analysis and interpretation, animal grouping and treatment, and manuscript preparation. MI: Concept, design, data collection, analysis and interpretation, data assembly, and manuscript preparation. MHJ: conception, data collection, and analysis and interpretation. LY: in vitro data collection and analysis. KCC: in vitro data collection and analysis. SN: provision of gintonin and critical idea for in vivo experiments. HH: basic in vitro data analysis. HR: provision and managing of critical idea for experiments and basic in vitro data analysis. MOK: provision of study material, data analysis and interpretation, administrative support, critical reading of manuscript and final approval of manuscript.

Corresponding authors

Correspondence to Hyewhon Rhim or Myeong Ok Kim.

Ethics declarations

The animals used in the experiment were handled in accordance with the animal ethics committee (IACUC) guidelines issued by the Division of Applied Life Sciences, Department of Biology at Gyeongsang National University, South Korea. The methods used for animal’s experiments were in accordance with the already-approved guidelines (Approval ID 125) by the animal ethics committee (IACUC) of the Division of Applied Life Sciences, Department of Biology at Gyeongsang National University, South Korea.

Conflict of Interest

The authors declare that they have no competing interests.

Additional information

This article has been retracted. Please see the retraction notice for more detail:https://doi.org/10.1007/s12035-024-04175-8

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Jo, M.G., Ikram, M., Jo, M.H. et al. RETRACTED ARTICLE: Gintonin Mitigates MPTP-Induced Loss of Nigrostriatal Dopaminergic Neurons and Accumulation of α-Synuclein via the Nrf2/HO-1 Pathway. Mol Neurobiol 56, 39–55 (2019). https://doi.org/10.1007/s12035-018-1020-1

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  • DOI: https://doi.org/10.1007/s12035-018-1020-1

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