###### Abstract  
We evaluated the effectiveness of _Scrophularia buregeriana_ extract (Brainon) on cognitive dysfunction and determined its underlying mechanisms in a scopolamine (SCO)-treated mouse model of memory impairment. Brainon treatment for 28 days ameliorated the symptoms of memory impairment as indicated by the results of both passive avoidance performance and the Morris water mazes. Brainon lowered acetylcholinesterasecholinesterase activity and raised acetylcholine levels in the hippocampus. The treatment elevated the protein levels of brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element-binding (CREE). Additionally, the excessive generation of SCO-induced reactive oxygen species (ROS) and subsequent oxidative stress were suppressed by the enhancement of superoxide dismutase (SOD)-1 and SOD-2 proteins. mRNA levels of upregulated interleukin (IL)-1B, IL-6, and tumor necrosis factor (TNF)-\(\alpha\), as well as the apoptotic protein Bcl-2-associated X protein (Bax), cleaved caspase-9, and cleaved poly adenosine diphosphate-ribose polymerase (PARP) expression after SCO injection were downregulated by Brainon treatment. Collectively, these findings suggested that Brainon possesses anti-amnesic effects through the CREB-BDNF pathway. Moreover, it exerted antioxidant, anti-inflammatory, and anti-apoptotic effects in SCO-induced mice exhibiting cognitive impairment and memory loss.  
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cascade, oxidative stress generation, and neuron cell death, including cholinergic malfunction, are causative factors in patients with neurodegenerative disorders. The hippocampus is susceptible to oxidative stress, and excessive oxidative stress induces memory deficiency by damaging synaptic plasticity and causing inflammation and neuronal cell death [7; 8]. SCO-treated mice showed oxidative stress-induced neuronal inflammation and apoptosis in the brain [9]. Therefore, SCO injection of animals is utilized as a useful pharmacological experimental model for cognitive degeneration and memory disorders in AD [2; 3; 4; 5].  
_Scrophularia puergeriana_ Miquel (SB), belonging to the Scrophulariaceae family, is indigenous to Korea and also found abundantly in China and Japan. In traditional medicine, dried SB roots have long been used to alleviate high fever, swollen skin, ob constipation, pharyngitis, neuro-inflammation, and throat infection [10]. SB roots have been found to contains various components such as E-harpagoside, 8-O-E-p-methoxycinnamoyl harpagide (MCA-Hg), E-p-methoxy-cinnamic acid (p-MCA), cinnamic acid, and angroside C. Moreover, we confirmed that Brainon exhibited significant neuroprotective effects against neurotoxicity caused SH-SY5Y cells by glutamate [11]. We previously demonstrated that Brainon exerts anti-amnesic effects via inhibition of amyloid beta accumulation and hyperphosphorylation of tau protein in memory deficit mice by \(\beta\)-amyloid [12].  
Therefore, we administrated 30 or 100 mg/kg Brainon based on the previous study [12] and confirmed the cognitive-improving activities of Brainon using passive avoidance performance and Morris water maze (MWM) task based on this research. To demonstrate the potential mechanism of Brainon, we confirmed the CREB-BDNF signaling pathway, AChE activity, and ACh levels in mice hippocampal tissue. Moreover, the anti-inflammatory and antioxidant effects of Brainon, as well as its effects on neuronal death, were evaluated in SCO-caused memory-impaired mice.