Morroni Fabiana, Sita Giulia, Djemil Alice, D'Amico Massimo, Pruccoli Letizia, Cantelli-Forti Giorgio, Hrelia Patrizia, Tarozzi Andrea
Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna , Bologna, Italy.
Department of Experimental, Diagnostic and Specialised Medicine, General Pathology Unit, Alma Mater Studiorum-University of Bologna , Bologna, Italy.
J Agric Food Chem. 2018 Jan 31;66(4):856-865. doi: 10.1021/acs.jafc.7b04641. Epub 2018 Jan 22.
Several studies suggest that an increase of glutathione (GSH) through activation of the transcriptional nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in the dopaminergic neurons may be a promising neuroprotective strategy in Parkinson's disease (PD). Among Nrf2 activators, isothiocyanate sulforaphane (SFN), derived from precursor glucosinolate present in Brassica vegetables, has gained attention as a potential neuroprotective compound. Bioavailability studies also suggest the contribution of SFN metabolites, including erucin (ERN), to the neuroprotective effects of SFN. Therefore, we compared the in vitro neuroprotective effects of SFN and ERN at the same dose level (5 μM) and oxidative treatment with 6-hydroxydopamine (6-OHDA) in SH-SY5Y cells. The pretreatment of SH-SY5Y cells with SFN recorded a higher (p < 0.05) active nuclear Nrf2 protein (12.0 ± 0.4 vs 8.0 ± 0.2 fold increase), mRNA Nrf2 (2.0 ± 0.3 vs 1.4 ± 0.1 fold increase), total GSH (384.0 ± 9.0 vs 256.0 ± 8.0 μM) levels, and resistance to neuronal apoptosis elicited by 6-OHDA compared to ERN. By contrast, the simultaneous treatment of SH-SY5Y cells with either SFN or ERN and 6-OHDA recorded similar neuroprotective effects with both the isothiocyanates (Nrf2 protein 2.2 ± 0.2 vs 2.1 ± 0.1 and mRNA Nrf2 2.1 ± 0.3 vs 1.9 ± 0.2 fold increase; total GSH 384.0 ± 4.8 vs 352.0 ± 6.4 μM). Finally, in vitro finding was confirmed in a 6-OHDA-PD mouse model. The metabolic oxidation of ERN to SFN could account for their similar neuroprotective effects in vivo, raising the possibility of using vegetables containing a precursor of ERN for systemic antioxidant benefits in a similar manner to SFN.
多项研究表明，通过激活多巴胺能神经元中的转录核因子（红细胞衍生2）样2（Nrf2）来增加谷胱甘肽（GSH）水平，可能是帕金森病（PD）一种有前景的神经保护策略。在Nrf2激活剂中，异硫氰酸萝卜硫素（SFN）来源于十字花科蔬菜中存在的前体硫代葡萄糖苷，作为一种潜在的神经保护化合物受到了关注。生物利用度研究还表明，SFN的代谢产物，包括芥酸（ERN），对SFN的神经保护作用有贡献。因此，我们比较了相同剂量水平（5 μM）的SFN和ERN在体外对经6-羟基多巴胺（6-OHDA）氧化处理的SH-SY5Y细胞的神经保护作用。与ERN相比，用SFN预处理SH-SY5Y细胞后，活性核Nrf2蛋白水平更高（p < 0.05）（增加12.0 ± 0.4倍 vs 8.0 ± 0.2倍），Nrf2 mRNA水平更高（增加2.0 ± 0.3倍 vs 1.4 ± 0.1倍），总GSH水平更高（384.0 ± 9.0 μM vs 256.0 ± 8.0 μM），并且对6-OHDA诱导的神经元凋亡的抗性更强。相比之下，用SFN或ERN与6-OHDA同时处理SH-SY5Y细胞时，两种异硫氰酸盐的神经保护作用相似（Nrf2蛋白增加2.2 ± 0.2倍 vs 2.1 ± 0.1倍，Nrf2 mRNA增加2.1 ± 0.3倍 vs 1.9 ± 0.2倍；总GSH 384.0 ± 4.8 μM vs 352.0 ± 6.4 μM）。最后，在6-OHDA-PD小鼠模型中证实了体外实验结果。ERN向SFN的代谢氧化可能解释了它们在体内相似的神经保护作用，这增加了使用含有ERN前体的蔬菜以类似于SFN的方式获得全身抗氧化益处的可能性。
