Morroni Fabiana, Sita Giulia, Tarozzi Andrea, Cantelli-Forti Giorgio, Hrelia Patrizia
Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna, via Irnerio 48, 40126 Bologna, Italy.
Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna, via Irnerio 48, 40126 Bologna, Italy.
Brain Res. 2014 Nov 17;1589:93-104. doi: 10.1016/j.brainres.2014.09.033. Epub 2014 Sep 23.
A number of pathogenic factors have been implicated in the progression of Parkinson׳s disease (PD), including oxidative stress, mitochondrial dysfunction, inflammation, excitotoxicity, and signals mediating apoptosis cascade. 6-(methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a major component in wasabi, a very popular spice in Japan and a member of the Brassica family of vegetables. This study was designed to investigate the neuroprotective effects of 6-MSITC in a PD mouse model. Mice were treated with 6-MSITC (5mg/kg twice a week) for four weeks after the unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA). On the 28th day, 6-OHDA-injected mice showed behavioral impairments, a significant decrease in tyrosine hydroxylase (TH) and an increase in apoptosis. In addition, lesioned mice showed reduced glutathione levels and glutathione-S-transferase and glutathione reductase activities. Notably, 6-MSITC demonstrated neuroprotective effects in our experimental model strongly related to the preservation of functional nigral dopaminergic neurons, which contributed to the reduction of motor dysfunction induced by 6-OHDA. Furthermore, this study provides evidence that the beneficial effects of 6-MSITC could be attributed to the decrease of apoptotic cell death and to the activation of glutathione-dependent antioxidant systems. These findings may render 6-MSITC as a promising molecule for further pharmacological studies on the investigation for disease-modifying treatment in PD.
帕金森病（PD）的进展涉及多种致病因素，包括氧化应激、线粒体功能障碍、炎症、兴奋性毒性以及介导凋亡级联反应的信号。异硫氰酸6-（甲基亚磺酰基）己酯（6-MSITC）是山葵中的主要成分，山葵是日本一种非常受欢迎的香料，属于十字花科蔬菜。本研究旨在探讨6-MSITC在帕金森病小鼠模型中的神经保护作用。在单侧纹状体内注射6-羟基多巴胺（6-OHDA）后，小鼠每周两次接受6-MSITC（5mg/kg）治疗，持续四周。在第28天，注射6-OHDA的小鼠出现行为障碍，酪氨酸羟化酶（TH）显著降低，凋亡增加。此外，损伤小鼠的谷胱甘肽水平以及谷胱甘肽-S-转移酶和谷胱甘肽还原酶活性降低。值得注意的是，6-MSITC在我们的实验模型中显示出神经保护作用，这与功能性黑质多巴胺能神经元的保留密切相关，有助于减少由6-OHDA诱导的运动功能障碍。此外，本研究提供了证据表明6-MSITC的有益作用可能归因于凋亡细胞死亡的减少以及谷胱甘肽依赖性抗氧化系统的激活。这些发现可能使6-MSITC成为进一步开展帕金森病疾病修饰治疗药理学研究的有前景的分子。
