###### Abstract  
_Scrophularia buegeriana_ (SB) Miq. (Scrophulariaceae) has been used to help cure swelling and fever and has reported antioxidant and neuro-protective effects. However, few mechanism-based studies have evaluated the memory-improving effects in a beta-amyloid induced memory loss model. As a result of _Scrophularia buegeriana_ extract (SBE) administration (30 and 100 mg/kg) for 28 days significantly recovered beta-amyloid-induced amnesia in the passive avoidance test and improved the impairment of spatial memory in the Morris Water Maze (MWM) task. Furthermore, SBE up-regulated superoxide dismutase-1 (SOD)-1, SOD-2, glutathione peroxidase-1, and B-cell lymphoma (Bcl)-2 protein expression levels. Additionally, SBE downregulated Bcl-2-associated X protein, cleaved caspase-9, cleaved poly (adenosine diphosphate-ribose) polymerase, and A\(\beta\) protein expression levels and inhibited the phosphorylation of the tau protein of A\(\beta\)-treated mice hippocampus. These results demonstrate that SBE improved memory impairment by reducing beta-amyloid induced neurotoxicity and regulated oxidative stress, anti-apoptotic pathways. srophularia buegeriana][PERSON]. [PERSON], [PERSON], [PERSON], [PERSON]  
SOD requires a metal cofactor, such as copper (Cu), zinc (Zn) and manganese (Mn), for activity as a metalloenzyme [9]. Cu/Zn-SOD (SOD1), which is located in chromosome 21 and encoded in the SOD1 gene located on chromosome 21 and predominantly occurs in the cytosolic compartment. Mn-SOD (SOD2), which is located in chromosome 6 and encoded in the SOD2 gene on chromosome 6, located in the mitochondrial matrix. The reduction of SOD-1 triggers oxidative cellular DNA damage, and SOD-2 protects mitochondrial DNA against damage due to oxidative stress [10]. GPx plays an import role in protecting cells from oxidative damage by converting hydrogen peroxide (H\({}_{2}\)O\({}_{2}\)) to H\({}_{2}\)O with glutathione (GSH) as a substrate, after the oxidation of GSH to Glutathione disulfide (GSSG). GR is known to maintain the reduced GSH level in redox cycle. Furthermore, it resists oxidative stress and maintains a reducing environment inside the cell [11; 12]. In addition, A\(\beta\)-mediated oxidative stress causes the hyper-phosphorylation of tau protein and affects neurofibrillary tangle formation. The accumulation of neurofibrillary tangles directly correlates with neuro-degeneration and cell death and is closely related to the severity of dementia [13; 14]. Apoptosis is mediated by two major pathways, which are divided into extrinsic and intrinsic pathways. Death receptors release several mitochondrial intermembrane proteins by passing death signaling to mitochondria in the intrinsic pathway [15]. A common mitochondria-related apoptotic pathway in neurons is regulated principally by the pro-apoptotic Bcl-2 protein family member, Bax. On receipt of the death signal, Bax is translocated to the mitochondria and interacts with the Bcl-2 family to control the progression of apoptosis [16; 17]. Bax activates down-stream effector caspases such as caspase-9 and caspase-poly (ADP) ribose polymerase (PARP) in vitro, and in vivo by stimulating cytochrome c release. Notably, Bcl-2 inhibits Bax-induced apoptosis [15; 18; 19]. _Scrophularia buegeriana_ (SB) Miq. (Scrophulariaceae), called Hyun-Sam in Korea, is used to help cure fever, swelling, constipation, pharyngitis, neuritis, and laryngitis as traditional medicine. SB dried root contains various components such as E-harpagoside (CAS: 19210-12-9), 8-O-E-p-methoxycinnamoyl harpagide (MCA-Hg), E-p-methoxycinnamic acid (p-MCA, CAS: 830-09-1), cinnamic acid (CAS: 140-10-3), and angoroside C (CAS: 115909-22-3), which displays neuro protective activities [11]. In a previous study, the SB extract (SBE) demonstrated cognition-enhancing activity in a scopolamine-induced short-term memory loss mice model [12]. However, investigation evaluating the effects of SBE in a beta-amyloid induced memory loss model is lacking.