P2‐259: Protection of neuron‐like PC12 cells from hydrogen peroxide‐induced cytotoxicity by Salvia sahendica

Oxidative stress has been implicated in the etiology of neurodegenerative diseases and aging. Reactive oxygen species readily damage biological molecules, which can ultimately lead to apoptotic or necrotic cell death. Epidemiological and in vitro studies strongly suggest that foods containing phytochemicals such as phenolic compounds have potential protective effects against many diseases, such as alzheimer's disease (AD). Cell viability was determined, using conventional MTT assay, in the presence of different concentrations (10, 25, 50 and 100 μg/ml) of methanolic extract of Salvia sehendica which is endemic to Iran. Oxidative stress was induced by hydrogen peroxide (150 μM). In vitro antioxidant assays, western blot analysis and enzyme activity assays of antioxidant proteins were performed to determine the mechanism of neuroprotection exerted by S. sahendica. The present study indicates that oxidative stress resulting from H2O2 can be inhibited in the presence of S. sahendica in a dose-dependent manner. This protection was associated with a marked reduction in caspase-3 activation. It was also found that S. sahendica elevates the glutathione level compared to H2O2-treated cells. This observation is likely due to upregulated expression of γ-GCS, mediator of the rate limiting step in GSH biosynthesis. On the other hand, the antioxidant enzymes those serve as a detoxifying system to prevent damage caused by ROS was greatly increased in the presence of S. sahendica; While PC12 cells treated with H2O2 caused the decrease in the activities of superoxide dismutase (SOD) and catalase (CAT) by about 3 fold, pretreatment with S. sahendica (100 μg/ml) significantly attenuated the decrease of SOD and CAT activity by about 2.39 and 3.24 fold, respectively. In addition, treatment of PC12 cells with H2O2 caused the increase in the intracellular MDA level by 1.74 fold, while preincubation of cells with S. sahendica markedly attenuated the change of MDA level. As oxidative stress is a critical event in the pathogenesis of neurodegenerative diseases, having neuroprotective effects along with antioxidant properties implies the possibility of using S. sahendica as a candidate for treating neurodegenerative diseases like AD.