Cargando…
Neuroprotective effect of Ginsenoside Re against neurotoxin-induced Parkinson's disease models via induction of Nrf2
The aim of the present study was to examine the neuroprotective effects of a panel of active components of ginseng and to explore their molecular mechanisms of action in two rotenone (Rot)-induced models of Parkinson's disease: An in vitro model using the human neuroblastoma cell line SH-SY5Y a...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9133950/ https://www.ncbi.nlm.nih.gov/pubmed/35543148 http://dx.doi.org/10.3892/mmr.2022.12731 |
Sumario: | The aim of the present study was to examine the neuroprotective effects of a panel of active components of ginseng and to explore their molecular mechanisms of action in two rotenone (Rot)-induced models of Parkinson's disease: An in vitro model using the human neuroblastoma cell line SH-SY5Y and an in vivo model using Drosophila. Ginsenoside Re (Re) was identified as the most potent inhibitor of Rot-induced cytotoxicity in SH-SY5Y cells by Cell Counting kit-8 assay and lactate dehydrogenase release assay. Flow cytometry, Hoechst staining, Rhodamine 123 staining, ATP and cytochrome c release revealed that Re rescue of Rot-induced mitochondrial dysfunction and inhibition of the mitochondrial apoptotic pathway. Western blot analysis demonstrated that Re alleviated Rot-induced oxidative stress by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) anti-oxidant pathway, and these effects were abolished by RNA interference-mediated knockdown of Nrf2. Re enhanced phosphorylation of components of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and extracellular regulated protein kinase (ERK) pathways, and pharmacological inhibition of these pathways reduced Re-mediated Nrf2 activation and neuroprotection. In the Drosophila model, Immunofluorescence microscopy, reactive oxygen species (ROS), hydrogen peroxide and knockdown analysis revealed that Re reversed Rot-induced motor deficits and dopaminergic neuron loss while concomitantly alleviating Rot-induced oxidative damage. The findings of the present study suggest that Re protects neurons against Rot-induced mitochondrial dysfunction and oxidative damage, at least in part, by inducing Nrf2/heme oxygenase-1 expression and activation of the dual PI3K/AKT and ERK pathways. |
---|