Zhang Ruyi, Sun Fangling, Zhang Lan, Sun Xuejing, Li Lin
a Department of Pharmacology, Xuanwu Hospital of Capital Medical University; Beijing Geriatric Medical Research Center; Beijing Institute for Brain Disorders; Beijing Engineering Research Center for Nerve System Drugs; Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China.
b Experimental Animal Laboratory, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.
Can J Physiol Pharmacol. 2017 Jun;95(6):750-758. doi: 10.1139/cjpp-2016-0209. Epub 2017 Feb 10.
Increasing evidence has solidified the involvement of α-synuclein (α-Syn) and neurotoxins in the pathogenesis of Parkinson's disease (PD), suggesting a combination of genetic and environmental influences. 2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) is one of the main active components extracted from Polygonum multiflorum. The purpose of the present study was to investigate the effects of TSG on α-Syn aggregation, mitochondrial dysfunction, oxidative stress, and apoptosis in vitro. A53T mutant α-synuclein-transfected cells (A53T AS cells) plus MPP exposure were used as a complex cell model of PD. The expression of proteins was determined by Western blot assay. Flow cytometry was utilized to measure mitochondrial membrane potential and apoptosis. The results showed that MPP exposure for 24 h induced more severe damage in A53T AS cells than in vector control cells. Pretreatment of TSG for 24 h significantly increased the cell viability; decreased lactate dehydrogenase leakage; inhibited α-Syn over-expression and aggregation; elevated mitochondrial membrane potential; decreased reactive oxygen species, Bax/Bcl-2 ratio, and caspase-3 activity; and inhibited apoptosis in A53T AS cells exposed to MPP. These results suggest that TSG may be an attractive candidate for PD therapy.
越来越多的证据证实了α-突触核蛋白（α-Syn）和神经毒素参与帕金森病（PD）的发病机制，这表明遗传和环境因素共同起作用。2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷（TSG）是从何首乌中提取的主要活性成分之一。本研究旨在探讨TSG对体外α-Syn聚集、线粒体功能障碍、氧化应激和细胞凋亡的影响。转染A53T突变型α-突触核蛋白的细胞（A53T AS细胞）加MPP处理被用作PD的复合细胞模型。通过蛋白质印迹法测定蛋白质表达。利用流式细胞术测量线粒体膜电位和细胞凋亡。结果表明，MPP处理24小时对A53T AS细胞造成的损伤比载体对照细胞更严重。TSG预处理24小时显著提高了细胞活力；减少了乳酸脱氢酶泄漏；抑制了α-Syn的过度表达和聚集；提高了线粒体膜电位；降低了活性氧、Bax/Bcl-2比值和caspase-3活性；并抑制了暴露于MPP的A53T AS细胞的凋亡。这些结果表明，TSG可能是一种有吸引力的PD治疗候选药物。
