Article ; Online: Vincamine alleviates brain injury by attenuating neuroinflammation and oxidative damage in a mouse model of Parkinson's disease through the NF-κB and Nrf2/HO-1 signaling pathways.
Journal of biochemical and molecular toxicology
2024 Volume 38, Issue 5, Page(s) e23714
Abstract: Parkinson's disease (PD) is a neurodegenerative disease featured by progressive loss of nigrostriatal dopaminergic neurons, the etiology of which is associated with the existence of neuroinflammatory response and oxidative stress. Vincamine is an indole ... ...
Abstract | Parkinson's disease (PD) is a neurodegenerative disease featured by progressive loss of nigrostriatal dopaminergic neurons, the etiology of which is associated with the existence of neuroinflammatory response and oxidative stress. Vincamine is an indole alkaloid that was reported to exhibit potent anti-inflammatory and antioxidant properties in many central and/or peripheral diseases. Nevertheless, the specific role of vincamine in PD development remains unknown. In our study, dopaminergic neuron loss was determined through immunohistochemistry staining and western blot analysis of tyrosine hydroxylase (TH) expression in the substantia nigra (SN) of PD mice. Reactive oxygen species (ROS) production and malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were detected through DHE staining and commercially available kits to assess oxidative stress. Pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) levels in the SN were measured via RT-qPCR and western blot analysis. Microglial and astrocyte activation was examined through immunofluorescence staining of Iba-1 (microglia marker) and GFAP (astrocyte marker) in the SN. The regulation of vincamine on the NF-κB and Nrf2/HO-1 pathway was estimated through western blot analysis. Our results showed that vincamine treatment decreased TNF-α, IL-1β, and IL-6 mRNA and protein levels, reduced GFAP and Iba-1 expression, decreased ROS production and MDA level, and increased SOD activity and GSH level in the SN of PD mice. Mechanically, vincamine repressed the phosphorylation levels of p65, IKKβ, and IκBα but enhanced the protein levels of Nrf2 and HO-1 in PD mice. Collectively, vincamine plays a neuroprotective role in PD mouse models by alleviating neuroinflammation and oxidative damage via suppressing the NF-κB pathway and activating the Nrf2/HO-1 pathway. |
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MeSH term(s) | Animals ; Mice ; Brain Injuries ; Interleukin-6/metabolism ; Neurodegenerative Diseases ; Neuroinflammatory Diseases ; NF-E2-Related Factor 2/metabolism ; NF-kappa B/metabolism ; Oxidative Stress ; Parkinson Disease/drug therapy ; Parkinson Disease/metabolism ; Reactive Oxygen Species ; Signal Transduction ; Superoxide Dismutase/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Vincamine/administration & dosage |
Chemical Substances | Interleukin-6 ; NF-E2-Related Factor 2 ; NF-kappa B ; Reactive Oxygen Species ; Superoxide Dismutase (EC 1.15.1.1) ; Tumor Necrosis Factor-alpha ; Vincamine (996XVD0JHT) |
Language | English |
Publishing date | 2024-04-17 |
Publishing country | United States |
Document type | Journal Article |
ZDB-ID | 1410020-4 |
ISSN | 1099-0461 ; 1095-6670 |
ISSN (online) | 1099-0461 |
ISSN | 1095-6670 |
DOI | 10.1002/jbt.23714 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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