Zhang Shuo, Ma Yan, Feng Juan
Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.
Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.
Neural Regen Res. 2020 Nov;15(11):2143-2153. doi: 10.4103/1673-5374.282264.
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.
反式-(-)-ε-葡萄素（ε-葡萄素）具有抗氧化和抗炎作用。它还通过激活SIRT3/LKB1/AMPK信号通路在亨廷顿病中发挥神经保护作用；然而，ε-葡萄素在帕金森病中是否也具有神经保护作用仍不清楚。通过将SH-SY5Y细胞暴露于3.0μM鱼藤酮24小时诱导建立帕金森病细胞模型，然后用1.0μMε-葡萄素处理细胞24小时。ε-葡萄素处理上调了SIRT3的表达，促进了FOXO3的去乙酰化和核定位。ε-葡萄素还增加了ATP的产生并减少了活性氧的产生。此外，ε-葡萄素处理减轻了鱼藤酮诱导的线粒体去极化并减少了细胞凋亡，并恢复了线粒体稳态相关蛋白的表达。然而，在鱼藤酮和ε-葡萄素处理之前用SIRT3或FOXO3 shRNA转染细胞时，这些变化被逆转。本研究结果表明，ε-葡萄素增强了SIRT3介导的FOXO3去乙酰化，降低了氧化应激，并维持了线粒体稳态，从而抑制了鱼藤酮诱导的细胞凋亡。因此，ε-葡萄素可能是一种有前景的帕金森病治疗策略。
