Neuroprotective effects of Scrophularia buergeriana extract against glutamate-induced toxicity in SH-SY5Y cells

Abstract

The aim of this study was to investigate the antioxidant and anti-apoptotic activities, as well as the underlying mechanisms of action, of Scrophularia buergeriana (S. buer‑ geriana) extract (SBE) in glutamate-induced SH-SY5Y cell death. The roots of S. buergeriana were extracted with 70% ethanol, and standardized SBE was used in this study. To induce cytotoxicity, the SH-SY5Y cells were exposed to glutamate for 3 h, or pre-treated with SBE for 1 h, and subsequently incubated with glutamate for 3 h. The neuroprotective effects were assessed by measuring cell viability and the total glutathione contents using commercial kits. The antioxidant and anti-apoptotic mechanisms of action of SBE were evaluated by western blot analysis. The results confirmed that glutamate-induced toxicity was caused by reactive oxygen species (ROS) production, leading to oxidative stress and DNA damage, thus leading to cell death. However, treatment of the SH‑SY5Y cells with SBE significantly increased the viability of the cells exposed to glutamate by upregulating the levels of antioxidant proteins, such as superoxide dismutase (SOD)1, SOD2 and glutathione peroxidase-1 (GPx-1), and directly enhancing the total glutathione contents. Furthermore, SBE attenuated DNA impairment and decreased B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax), cleaved caspase-3 and cleaved poly(adenosine diphosphate (ADP)-ribose) polymerase (PARP) activation. In addition, SBE upregulated Bcl-2 expression via p38 mitogen-activated protein kinases (MAPKs). On the whole, the findings of this study demonstrated that SBE exerts neuroprotective effects against glutamate-induced cell toxicity through its antioxidant and anti-apoptotic activities.