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

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.

• Authors: Min Gi Jo, Muhammad Ikram, Myeung Hoon Jo, Lang Yoo, Kwang Chul Chung, Seung-Yeol Nah, Hongik Hwang, Hyewhon Rhim, Myeong Ok Kim
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 56 Issue 1 Pg. 39-55 (Jan 2019) ISSN: 1559-1182 [Electronic] United States
• PMID: 29675576 (Publication Type: Journal Article, Retracted Publication)

Chemical References

• Biomarkers
• Glial Fibrillary Acidic Protein
• Inflammation Mediators
• NF-E2-Related Factor 2
• Neuroprotective Agents
• Neurotoxins
• Plant Extracts
• alpha-Synuclein
• gintonin
• Rotenone
• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Heme Oxygenase-1
• Tyrosine 3-Monooxygenase

Topics

• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Animals
• Apoptosis (drug effects)
• Biomarkers (metabolism)
• Cell Line, Tumor
• Corpus Striatum (pathology, physiopathology)
• Disease Models, Animal
• Dopaminergic Neurons (metabolism, pathology)
• Glial Fibrillary Acidic Protein (metabolism)
• Gliosis (complications, pathology, physiopathology)
• Heme Oxygenase-1 (metabolism)
• Humans
• Inflammation Mediators (metabolism)
• Male
• Mice, Inbred C57BL
• Motor Activity (drug effects)
• NF-E2-Related Factor 2 (metabolism)
• Neuroprotective Agents (pharmacology)
• Neurotoxins (toxicity)
• Oxidative Stress (drug effects)
• Parkinson Disease (complications, pathology, physiopathology)
• Plant Extracts (pharmacology)
• Rotenone
• Signal Transduction (drug effects)
• Substantia Nigra (pathology, physiopathology)
• Tyrosine 3-Monooxygenase (metabolism)
• Up-Regulation (drug effects)
• alpha-Synuclein (metabolism)