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

Min Gi Jo, Muhammad Ikram, Myeung Hoon Jo, Lang Yoo, Kwang Chul Chung, Seung Yeol Nah, Hongik Hwang, Hyewhon Rhim, Myeong Ok Kim

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26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)39-55
Number of pages17
JournalMolecular Neurobiology
Volume56
Issue number1
DOIs
Publication statusPublished - 2019 Jan 1

Bibliographical note

Funding Information:
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).

All Science Journal Classification (ASJC) codes

  • Neurology
  • Cellular and Molecular Neuroscience

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