Neuroprotective mechanisms of ϵ-viniferin in a rotenone-induced cell model of Parkinson's disease: Significance of SIRT3-mediated FOXO3 deacetylation

Abstract

Trans-(-)-ϵ-viniferin (ϵ-viniferin) has antioxidative and anti-inflammatory effects. It also has neuroprotective effects in Huntington's disease by activating the SIRT3/LKB1/AMPK signaling pathway; however, it remains unknown whether ϵ-viniferin also has a neuroprotective role in Parkinson's disease. A Parkinson's disease cell model was induced by exposing SH-SY5Y cells to 3.0 μM rotenone for 24 hours, and cells were then treated with 1.0 μM ϵ-viniferin for 24 hours. Treatment with ϵ-viniferin upregulated SIRT3 expression, which promoted FOXO3 deacetylation and nuclear localization. ϵ-Viniferin also increased ATP production and decreased reactive oxygen species production. Furthermore, ϵ-viniferin treatment alleviated rotenone-induced mitochondrial depolarization and reduced cell apoptosis, and restored the expression of mitochondrial homeostasis-related proteins. However, when cells were transfected with SIRT3 or FOXO3 shRNA prior to rotenone and ϵ-viniferin treatment, these changes were reversed. The results from the present study indicate that ϵ-viniferin enhances SIRT3-mediated FOXO3 deacetylation, reduces oxidative stress, and maintains mitochondrial homeostasis, thus inhibiting rotenone-induced cell apoptosis. ϵ-Viniferin may therefore be a promising treatment strategy for Parkinson's disease.