Gintonin Mitigates MPTP-Induced Loss of Nigrostriatal Dopaminergic Neurons and Accumulation of -Synuclein via the Nrf2/HO-1 Pathway
- Jo, Min Gi; Ikram, Muhammad; Jo, Myeung Hoon; Yoo, Lang; Chung, Kwang Chul; Nah, Seung-Yeol; Hwang, Hongik; Rhim, Hyewhon; Kim, Myeong Ok
- Issue Date
- Gintonin; Neuroprotection; Nrf2; HO-1 pathway; Parkinson' s disease; MPTP; Neuroinflammation
- MOLECULAR NEUROBIOLOGY, v.56, no.1, pp.39 - 55
- Journal Title
- MOLECULAR NEUROBIOLOGY
- Start Page
- End Page
- 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 -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 -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.
- Files in This Item
- There are no files associated with this item.
- Appears in
- ETC > Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.