• The Korea Journal of Herbology
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• v.30 no.1
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• pp.67-75
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• 2015

Objectives : The aim of this study is to examine the neuroprotective effect of wheat bran extract (WBE) against ${\beta}$-amyloid ($A{\beta}$)-induced apoptotic cell death in SH-SY5Y human neuroblastoma cells and memory impairment in triple transgenic animal model's of Alzheimer's disease (3xTg AD mice). Methods : In SH-SY5Y cells, MTT assay and TUNEL staining were conducted to evaluate the protective effect of WBE against $A{\beta}_{25-35}$-induced neurotoxicity and apoptosis. Alterations in mitochondrial transmembrane potential (MMP), expression of proapoptotic Bax and antiapoptotic Bcl-2 proteins, cleavage of PARP, and brain-derived neurotrophic factor (BDNF) levels were analyzed to elucidate the neuroprotective mechanism of WBE. To further investigate the memory enhancing effect of WBE, Morris water maze test was performed in 3xTg AD mice. Results : In SH-SY5Y cells, WBE protected against $A{\beta}_{25-35}$-caused cytotoxicity and apoptosis as shown by the restoration of cell viability in MTT assay and inhibition of DNA fragmentation in TUNEL staining. $A{\beta}_{25-35}$-induced apoptotic signals such as dissipation of MMP, decreased Bcl-2/Bax ratio, and cleavage of PARP were suppressed by WBE. Moreover, WBE up-regulated the protein levels of BDNF, which seemed to be mediated by activation of cAMP response element-binding protein (CREB). In 3xTg AD mice, oral administration of WBE attenuated learning and memory deficit as verified by reduced mean escape latency in water maze test. Conclusions : WBE protects neuronal cells from $A{\beta}_{25-35}$-induced apoptotic cell death and restores learning and memory impairments in 3xTg AD mice. These findings suggest that WBE exhibit neuroprotective potential for the management of AD.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.2
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• pp.228-235
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• 2010

This study was performed to investigate the memory enhancing effect of Poria cocos Wolf (Hoelen cum radix) against scopolamine-induced amnesia in Sprague-Dawley (SD) rats. To induce amnesia, scopolamine (0.75 mg/kg) was intraperitonically injected into SD rats 30 min before starting behavior tests. We have conducted Morris water-maze and Y-maze tests to monitor learning and memory functions. Poria cocos effectively reversed scopolamine-induced memory impairment in SD rats which was represented by an improvement of mean escape latency in water-maze test and spontaneous alterations in Y-maze test. To elucidate possible molecule mechanism, we have measured mRNA as well as protein expression of acetylcholine esterase (AchE), choline acetyltransferase (ChAT), muscarinic acetylcholine receptor (mAchR), and brain-derived neurotrophic factor (BDNF) using RT-PCR and Western blot analysis, respectively. Poria cocos increased mRNA levels of ChAT and mAchR in rat hippocampus compared with those in the scopolamine-injected amnesic group. In addition, protein expression of ChAT and BDNF was also elevated by Poria cocos intake. Furthermore, as an upstrem regulator, the activation of cAMP response element-binding protein (CREB) was assessed by immunohistochemistry. In this immunohistochemical analysis, the phosphorylation of CREB (p-CREB) was reduced by scopolamine injection, which was restored back to control levels by administration of Poria cocos. These results suggest that Poria cocos may improve memory and cognitive deficit in amnesia and have therapeutic potentials through up-regulation of ChAT, mAchR, and BDNF, which seemed to be mediated by activation of CREB.

• Journal of Ginseng Research
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• v.38 no.1
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• pp.1-7
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• 2014

Background: Although ginsenosides such as Rg1, Rb1 and Rg3 have shown promise as potential nutraceuticals for cognitive impairment, their use has been limited due to high production cost and low potency. In particular, the process of extracting pure Rg3 from ginseng is laborious and expensive. Methods: We described the methods in preparing ginseol k-g3, an Rg3-enriched fraction, and evaluated its effects on scopolamine-induced memory impairment in mice. Results: Ginseol k-g3 (25-200 mg/kg) significantly reversed scopolamine-induced cognitive impairment in the passive avoidance, but not in Y-maze testing. Ginseol k-g3 (50 and 200 mg/kg) improved escape latency in training trials and increased swimming times within the target zone of the Morris water maze. The effect of ginseol k-g3 on the water maze task was more potent than that of Rg3 or Red ginseng. Acute or subchronic (6 d) treatment of ginseol k-g3 did not alter normal locomotor activity of mice in an open field. Ginseol k-g3 did not inhibit acetylcholinesterase activity, unlike donezepil, an acetylcholinesterase inhibitor. Rg3 enrichment through the ginseol k-g3 fraction enhanced the efficacy of Rg3 in scopolamine-induced memory impairment in mice as demonstrated in the Morris water maze task. Conclusion: The effects of ginseol k-g3 in ameliorating scopolamine-induced memory impairment in the passive avoidance and Morris water maze tests indicate its specific influence on reference or long-term memory. The mechanism underlying the reversal of scopolamine-induced amnesia by ginseol k-g3 is not yet known, but is not related to anticholinesterase-like activity.

• Journal of Life Science
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• v.29 no.5
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• pp.564-569
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• 2019

Heavy drinking disrupts the nervous system by activation of GABA receptors and inhibition of glutamate receptors, thereby preventing short-term memory formation. Degradation of cognition by alcohol induces blackouts, and it can lead to alcoholic dementia if repeated. Therefore, drugs need to be developed to prevent alcohol-induced blackout. In this study, we confirmed the effect of an ethanol extract of Cassia obtusifolia seeds (COE) on alcohol-induced memory impairment. The effects of COE and ethanol on cognitive functions mice were examined using the passive avoidance and Y-maze tests. The manner in which alcohol affects long-term potentiation (LTP) in relation to the learning and memory was confirmed by electrophysiology performed on mouse hippocampal slices. We also measured N-methyl-D-aspartate (NMDA) receptor-mediated field excitatory synapses (fEPSPs), which have a known association with cognitive impairment caused by ethanol. Ethanol caused memory impairments in passive avoidance and Y-maze tests. COE prevented these ethanol-induced memory impairments in these tests. Ethanol also blocked LTP induction in the mouse hippocampus, and COE prevented this ethanol-induced LTP deficit. Ethanol decreased NMDA receptor-mediated fEPSPs in the mouse hippocampus, and this decrease was prevented by COE. These results suggest that COE might be useful in preventing alcohol-induced neurological dysfunctions, including blackouts.

• Journal of Physiology & Pathology in Korean Medicine
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• v.35 no.3
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• pp.97-103
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• 2021

Perilla frutescens (P. frutescens) is an important herb used for many purposes such as medicinal, aromatic, and functional food in Asian countries and has beneficial effects such as antioxidant activity, anti-inflammation activity, anti-depression activity, and anxiolytic activity. However, there have been no studies on the protective effect of P. frutescens extract (PFE) on amnesia in vivo. The present study aimed to investigate whether PFE protects memory deficit using a scopolamine-induced mice model and elucidate the underlying mechanisms involved. The protective effect of PFE against scopolamine-induced memory deficits was investigated using Y-maze, passive avoidance, and Morris water maze tests. Furthermore, the potential mechanisms of PFE in improving memory capabilities related to the cholinergic system and antioxidant activity were examined. PFE significantly increased spontaneous alternation in the Y-maze test, step-through latency in the passive avoidance test, and swimming time in the target quadrant in the probe test when compared to the scopolamine-treated group. Likewise, PFE significantly decreased escapes latency in the Morris water maze test. PFE could not regulate cholinergic function in acetylcholine level and acetylcholine esterase activity. However, PFE increased DPPH radical scavenging activity dose-dependently and total polyphenol content was 127.7±1.2 ㎍ GAE/mg. The results showed that the PFE could be a preventive and/or therapeutic candidate for memory and cognitive dysfunction in Alzheimer's disease.

• Clinical and Experimental Pediatrics
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• v.55 no.10
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• pp.383-387
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• 2012

Purpose: Although benign rolandic epilepsy (BRE) is a benign condition, it may be associated with a spectrum of behavioral, psychiatric, and cognitive disorders. This study aimed to assess the cognitive and other neuropsychological profiles of children with BRE. Methods: In total, 23 children with BRE were consecutively recruited. All children underwent sleep electroencephalography (EEG) and were assessed on a battery of comprehensive neuropsychological tests including the Korean versions of the Wechsler intelligence scale for children III, frontal executive neuropsychological test, rey complex figure test, Wisconsin card sorting test, attention deficit diagnostic scale, and child behavior checklist scale. Results: The study subjects included 13 boys and 10 girls aged $9.0{\pm}1.6$ years. Our subjects showed an average monthly seizure frequency of $0.9{\pm}0.7$, and a majority of them had focal seizures (70%). The spike index (frequency/min) was $4.1{\pm}5.3$ (right) and $13.1{\pm}15.9$ (left). Of the 23 subjects, 9 showed frequent spikes (>10/min) on the EEG. The subjects had normal cognitive and frontal executive functions, memory, and other neuropsychological sub-domain scores, even though 8 children (35%) showed some evidence of learning difficulties, attention deficits, and aggressive behavior. Conclusion: Our data have limited predictive value; however, these data demonstrate that although BRE appears to be benign at the onset, children with BRE might develop cognitive, behavioral, and other psychiatric disorders during the active phase of epilepsy, and these problems may even outlast the BRE. Therefore, we recommend scrupulous follow-up for children with BRE.

• Journal of Microbiology and Biotechnology
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• v.31 no.1
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• pp.51-62
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• 2021

Here, we investigated the prebiotic and antioxidant effects of Actinidia arguta sprout water extract (AASWE) on lipopolysaccharide (LPS)-induced cognitive deficit mice. AASWE increased viable cell count, titratable acidity, and acetic acid production in Lactobacillus reuteri strain and showed a cytoprotective effect on LPS-induced inflammation in HT-29 cells. We assessed the behavior of LPS-induced cognitive deficit mice using Y-maze, passive avoidance and Morris water maze tests and found that administration of AASWE significantly improved learning and memory function. The AASWE group showed antioxidant activity through downregulation of malondialdehyde levels and upregulation of superoxide dismutase levels in brain tissue. In addition, the AASWE group exhibited activation of the cholinergic system with decreased acetylcholinesterase activity in brain tissue. Furthermore, AASWE effectively downregulated inflammatory mediators such as phosphorylated-JNK, phosphorylated-NF-κB, TNF-α and interleukin-6. The major bioactive compounds of AASWE were identified as quercetin-3-O-arabinopyranosyl(1→2)-rhamnopyranosyl(1→6)-glucopyranose, quercetin-3-O-apiosyl(1 → 2)-galactoside, rutin, and 3-caffeoylquinic acid. Based on these results, we suggest that AASWE not only increases the growth of beneficial bacteria in the intestines, but also shows an ameliorating effect on LPS-induced cognitive impairment.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.1
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• pp.47-57
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• 2022

Stiripentol is an anti-epileptic drug for the treating of refractory status epilepticus. It has been reported that stiripentol can attenuate seizure severity and reduce seizure-induced neuronal damage in animal models of epilepsy. The objective of the present study was to investigate effects of post-treatment with stiripentol on cognitive deficit and neuronal damage in the cornu ammonis 1 (CA1) region of the hippocampus proper following transient ischemia in the forebrain of gerbils. To evaluate ischemia-induced cognitive impairments, passive avoidance test and 8-arm radial maze test were performed. It was found that post-treatment with stiripentol at 20 mg/kg, but not 10 or 15 mg/kg, reduced ischemia-induced memory impairment. Transient ischemia-induced neuronal death in the CA1 region was also significantly attenuated only by 20 mg/kg stiripentol treatment after transient ischemia. In addition, 20 mg/kg stiripentol treatment significantly decreased ischemia-induced astrocyte damage and immunoglobulin G leakage. In brief, stiripentol treatment after transient ischemia ameliorated transient ischemia-induced cognitive impairment in gerbils, showing that pyramidal neurons were protected and astrocyte damage and blood brain barrier leakage were significantly attenuated in the hippocampus. Results of this study suggest stiripentol can be developed as a candidate of therapeutic drug for ischemic stroke.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.22 no.4
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• pp.253-261
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• 2011

Objectives : This study aimed to investigate the efficacy and safety of Metadate CD (MCD) when given to Korean children and adolescents with attention-deficit hyperactivity disorder (ADHD). We also explored the effects of the drug on diverse neuro-cognitive functions. Methods : Ninety-one subjects with ADHD (mean age 8.6${\pm}$2.2 years) were recruited at 6 outpatient clinics in Seoul, Korea. We used the ADHD Rating Scale (ARS), Clinical Global Impression (CGI), and comprehensive attention test (CAT) to measure the drug's effects. Results : After 0.92${\pm}$0.32mg/kg/day of MCD were administered for 57.4${\pm}$7.6 days, there was a 48.5% reduction in the mean total ARS scores (p<.001). Fifty-seven subjects (64.8%) showed either much improved or very much improved outcomes on the CGI-Improvement scale. The CGI-Severity scale also decreased from an average of 4.7 to an average of 2.9 (p<.001). Errors and response time standard deviations of the CAT, sustained attention test-to-response tasks, the flanker test, and divided attention test scores decreased after treatment (p<.05). The forward memory span of the spatial working memory test scores increased (p<.05). Thirty-five patients (39.8%) experienced side effects, of which the most common were headache (14.8%), nausea (12.5%), and anorexia (9.1%). Conclusion : This open-label study suggests that MCD is effective and safe in improving the symptoms and neurocognitive functions of Korean children and adolescents with ADHD.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.8 no.2
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• pp.273-286
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• 1997

Objective：This study was designed to evaluate effects of methylphenidate(MPH) on event-related potentials(ERP) and continuous performance test(CPT) in attention-deficit hyperactivity disorder (ADHD) and to see the correlation between changes in ERP and changes in performance. Method：ERP and CPT were used to examine the acute effects of MPH(0.5mg/kg) in eleven ADHD boys(89-103 months old). Results：1) After MPH administration, P3 latency to nontarget stimuli at Fz was significantly decreased (p<0.01) and P2 amplitudes to target stimuli at Pz and at Oz and P3 amplitude to target stimuli at Cz were significantly increased(p<0.05). 2) Commission error and omission error in the CPT-X and commission error in the CPT-AX were decreased(p<0.01), and hits and perceptual sensitivity(d') in the CPT-X and d′ in the CPT-AX were increased(p<0.01). 3) The change of P3 latency to nontarget stimuli at Fz and the change of d′ in the CPT-X were negatively correlated(p<0.05), and the change of P2 amplitude to target stimuli at Pz and d′ in the CPT-AX were positively correlated(p<0.05). Conclusion：MPH improves change orienting reaction, the delivery of task relevant information, accuracy and perceptual sensitivity in ADHD. And the increase of ability to discriminate targets from non-targets reflects reduced evaluation time in large memory component task and enhanced change orienting reaction in simple task.