Li Xu-zhao, Zhang Shuai-nan, Wang Ke-xin, Liu Hong-yu, Yang Zhi-ming, Liu Shu-min, Lu Fang
Chinese Medicine Toxicological Laboratory, Institute of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin 150040, PR China.
School of Basic Medical Sciences, Nanjing University of Chinese Medicine, Nanjing 210046, PR China.
Phytomedicine. 2014 Apr 15;21(5):704-11. doi: 10.1016/j.phymed.2013.10.012. Epub 2013 Nov 16.
Extract of Acanthopanax senticosus harms (EAS) has been shown to have neuroprotective effects on dopaminergic neurons in Parkinson's disease (PD) mice model. α-Synuclein is a key player in the pathogenesis of PD, the elevated level of which is deleterious to dopaminergic neurons, and enhancing its clearance might be a promising strategy for treating PD. To assess the potential of EAS in this regard, we investigated its effect on the SH-SY5Y cells overexpressing wild-type α-synuclein (WT-α-Syn) or A53T mutant α-synuclein (A53T-α-Syn), and the implicated pathway it might mediate. After treatment with EAS, the changes of α-synuclein, caspase-3, parkin, phospho-protein kinase B (Akt), phospho-glycogen synthase kinase 3 beta (GSK3β), and phospho-microtubule-associated protein tau (Tau) in WT-α-Syn or A53T-α-Syn transgenic cells were reverted back to near normal levels, demonstrated by the western blotting and quantitative real-time PCR outcomes. The neuroprotective effects of EAS may be able to protect WT-α-Syn or A53T-α-Syn transgenic SH-SY5Y cells from α-synuclein overexpression and toxicity. Therefore, we speculate that EAS might be a promising candidate for prevention or treatment of α-synuclein-related neurodegenerative disorders such as PD.
刺五加提取物（EAS）已被证明对帕金森病（PD）小鼠模型中的多巴胺能神经元具有神经保护作用。α-突触核蛋白是PD发病机制中的关键因素，其水平升高对多巴胺能神经元有害，提高其清除率可能是治疗PD的一种有前景的策略。为了评估EAS在这方面的潜力，我们研究了它对过表达野生型α-突触核蛋白（WT-α-Syn）或A53T突变型α-突触核蛋白（A53T-α-Syn）的SH-SY5Y细胞的影响，以及它可能介导的相关途径。用EAS处理后，通过蛋白质免疫印迹和定量实时PCR结果表明，WT-α-Syn或A53T-α-Syn转基因细胞中α-突触核蛋白、半胱天冬酶-3、帕金蛋白、磷酸化蛋白激酶B（Akt）、磷酸化糖原合酶激酶3β（GSK3β）和磷酸化微管相关蛋白tau（Tau）的变化恢复到接近正常水平。EAS的神经保护作用可能能够保护WT-α-Syn或A53T-α-Syn转基因SH-SY5Y细胞免受α-突触核蛋白过表达和毒性的影响。因此，我们推测EAS可能是预防或治疗如PD等α-突触核蛋白相关神经退行性疾病的有前景的候选药物。
