State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.
Phytomedicine. 2013 Sep 15;20(12):1064-70. doi: 10.1016/j.phymed.2013.04.017. Epub 2013 Jun 6.
Oxidative stress plays an important role in the pathological processes of various neurodegenerative diseases. In this study, we investigated the neuroprotective effects of (M)-bicelaphanol A, which has been the first dimeric podocarpane type trinorditerpene isolated from Celastrus orbiculatus, against hydrogen peroxide (H2O2)-induced injury in human SH-SY5Y neuroblastoma cells. Our study showed that cells pretreated with (M)-bicelaphanol A significantly attenuated H2O2-induced cell viability reduction and cell apoptosis. These neuroprotective effects of (M)-bicelaphanol A were associated with a reduction of reactive oxygen species and an increase in the level of adenosine triphosphate. In addition, (M)-bicelaphanol A pretreatment markedly increased the phosphorylation level of Akt in SH-SY5Y cells. In conclusion, our results for the first time demonstrate that the protection of (M)-bicelaphanol A on SH-SY5Y cells against H2O2-induced oxidative stress may attribute, at least partially, to its attenuation of mitochondrial dysfunction and activation of Akt signaling pathway. Above results shed more light on the molecular mechanisms involved in the neuroprotective effects of (M)-bicelaphanol A, which could be a potential drug candidate for the treatment of oxidative stress-associated neurodegenerative diseases.
氧化应激在各种神经退行性疾病的病理过程中起着重要作用。在这项研究中,我们研究了(M)-双石蒜醇 A 的神经保护作用,它是从南蛇藤中分离出的第一个二聚 podocarpane 型三萜。(M)-双石蒜醇 A 预处理可显著减轻过氧化氢(H2O2)诱导的人 SH-SY5Y 神经母细胞瘤细胞活力降低和细胞凋亡。这些神经保护作用与活性氧的减少和三磷酸腺苷水平的增加有关。此外,(M)-双石蒜醇 A 预处理可显著增加 SH-SY5Y 细胞中 Akt 的磷酸化水平。总之,我们的研究结果首次表明,(M)-双石蒜醇 A 对 SH-SY5Y 细胞的保护作用可以减轻氧化应激引起的损伤,这至少部分归因于其对线粒体功能障碍的抑制和 Akt 信号通路的激活。上述结果为(M)-双石蒜醇 A 的神经保护作用的分子机制提供了更多的了解,它可能是治疗与氧化应激相关的神经退行性疾病的潜在药物候选物。