Wan Jingzhi, Deng Lili, Zhang Changcheng, Yuan Qin, Liu Jing, Dun Yaoyan, Zhou Zhiyong, Zhao Haixia, Liu Chaoqi, Yuan Ding, Wang Ting
a College of Medical Science, Three Gorges University, Yichang, Hubei 443002, China.
b Three Gorges University Institute of Molecular Biology, Yichang, Hubei 443002, China.
Can J Physiol Pharmacol. 2016 Sep;94(9):919-28. doi: 10.1139/cjpp-2015-0262. Epub 2016 Apr 19.
Oxidative stress plays a vital role in the pathogenesis of neurodegenerative diseases. Chikusetsu saponin V (CsV), the most abundant member of saponins from Panax japonicus (SPJ), has attracted increasing attention for its potential to treat neurodegenerative diseases. However, the mechanisms are unclear. Our study intended to investigate the antioxidative effects of CsV in human neuroblastoma SH-SY5Y cells. Our data showed that CsV attenuated H2O2-induced cytotoxicity, inhibited ROS accumulation, increased the activities of superoxide dismutase (SOD) and GSH, and increased mitochondrial membrane potential dose-dependently. Further exploration of the mechanisms showed that CsV exhibited these effects through increasing the activation of oxidative-stress-associated factors including Sirt1, PGC-1α, and Mn-SOD. Moreover, CsV inhibited H2O2-induced down-regulation of Bcl-2 and up-regulation of Bax in a dose-dependent manner and, thus, increased the ratio of Bcl-2/Bax. In conclusion, our study demonstrated that CsV exhibited neuroprotective effects possibly through Sirt1/PGC-1α/Mn-SOD signaling pathways.
氧化应激在神经退行性疾病的发病机制中起着至关重要的作用。竹节参皂苷V(CsV)是竹节参皂苷(SPJ)中含量最丰富的成员,因其治疗神经退行性疾病的潜力而受到越来越多的关注。然而,其作用机制尚不清楚。我们的研究旨在探讨CsV对人神经母细胞瘤SH-SY5Y细胞的抗氧化作用。我们的数据表明,CsV可减轻H2O2诱导的细胞毒性,抑制活性氧积累,剂量依赖性地增加超氧化物歧化酶(SOD)和谷胱甘肽(GSH)的活性,并增加线粒体膜电位。对其机制的进一步探索表明,CsV通过增加包括Sirt1、PGC-1α和锰超氧化物歧化酶(Mn-SOD)在内的氧化应激相关因子的激活来发挥这些作用。此外,CsV剂量依赖性地抑制H2O2诱导的Bcl-2下调和Bax上调,从而增加Bcl-2/Bax比值。总之,我们的研究表明,CsV可能通过Sirt1/PGC-1α/Mn-SOD信号通路发挥神经保护作用。