## 4 Discussion  
Previously, we reported that SBE extracts demonstrate potent anti-amnesic activity and anti-apoptotic effects in a scopolamine-induced memory impairment mouse model and in the SH-SYSY cell line [11; 12]. In vitro studies have shown that SBE treatment inhibited cell death induced by glutamate. Furthermore, the in vivo study indicates that acute and prolonged treatment with SBE demonstrates the highest anti-oxidant activity in the scopolamine-induced memory impairment model. However, research on amyloid-beta, which affects in the development of AD, is insufficient. The first report aimed to identify the neuro-protective activities, including amyloid-beta accumulation prevention effects and related mechanisms of chronic SBE administration in the A\(\beta\) 1-42-induced cognitive deficit mice model. AD is a progressive, neurodegenerative disorder that causes damage to the brain and is characterized by cognitive decline, and irreversible memory loss. Amyloid-beta peptides, and hyper-phosphorylated tau protein comprising neurofibrillary tangles have been considered critical factors of pathological hallmarks of AD [10]. Indeed, A\(\beta\) levels were higher in the brain of AD patients than normal aged brain samples, indicating clinical signs such as spatial memory loss [20; 21]. To assess cognitive deficits, passive avoidance and MWM tasks were performed to investigate learning and memory skills. The passive avoidance task is used to confirm the memory function by measuring the escape time from the space. The MWM task is the most widely used laboratory behavioral test to assess hippocampal-dependent cognitive deficits and learning functions in mice and rats [20; 22; 23]. Injection of A\(\beta\) 1-42 resulted in severe cognitive impairments and memory loss in the passive avoidance test and MWM, as well as neurodegeneration. However, SBE treatment dose-dependently increased the step-through latency in the passive avoidance task and decreased escape latency and swim distance significantly for 4 days of MWM trials. This implied that SBE  
Figure 7: Effects of SBE on amyloid-beta protein expression levels and phosphorylation of tau protein levels in the hippocampus of memory-impaired mice. (**A**) The expression of amyloid-beta (A\(\beta\)) and phospho (p)-tau was detected by Western blotting analysis. (**B**) The protein bands were quantified and calculated using the software. Phosphorylation levels of the tau protein were normalized to those of tau, and A\(\beta\) protein expression level was normalized on \(\beta\)-actin level. The data are expressed as means \(\pm\) SEM of independent experiments (\(n=3\)). #\(p<0.01\) vs. Control group; $\(\$<0.01\) vs. Control group; **\(p<0.01\) vs. A\(\beta\) (1–42) group. administration improves cognitive performance and ameliorates memory deficits, although not as completely as the normal model that did not cause memory loss. In the previous study, we have demonstrated that neuronal cell death and cognitive deficiency due to oxidative stress are related to A\(\beta\) accumulation in the brain. [24]. A\(\beta\) is a known neuro-toxic peptide that promotes oxidative stress and lipid peroxidation in the intermembrane and also causes ROS generation by serving as a source of ROS [5; 6; 25]. The accumulation of A\(\beta\) may result in an increased production of ROS, subsequently leading to neuronal death through apoptotic pathways [25; 26]. To prevent ROS generation and regulate the steady-state O\({}^{2}\) concentration, cells have anti-oxidant defense systems such as SODs, GR and GPx-1 enzymes [11; 12; 27]. A\(\beta\) 1-42 injection attenuated hippocampal antioxidant enzyme activities and protein expression levels, the same as in previous studies [28; 29]. Nevertheless, we observed that the administration of SBE (30, 100 mg/kg) could significantly enhance GR activity and SODs, GPx-1 protein levels in the A\(\beta\) 1-42-treated mouse hippocampus.