• 한국식품과학회지
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• 제52권3호
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• pp.263-273
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• 2020

본 연구에서는 양파(Allium Cepa L.) 과육과 과피를 이용하여 in vitro 신경세포 보호효과 및 Aβ로 유도된 인지기능 장애 마우스 모델에서의 개선효과를 검증하고자 하였다. 양파 과육 분획물(EOF)과 과피 분획물(EOP) 모두 PC-12 세포에서 Aβ로 유도된 세포 독성에 대하여 신경세포 보호효과(세포 내 산화적 스트레스 억제, 세포 생존율 및 세포막 보호효과)를 나타냈다. Aβ로 유도된 인지장애 마우스 모델에서의 행동실험(Y-미로, 수동회피 및 Morris 수중 미로 시험) 결과 또한 양파 과육 분획물(EOF)과 과피 분획물(EOP) 모두 효과적인으로 학습 및 기억능력을 개선시키는 것으로 나타났다. 행동실험 후 마우스 뇌조직에서의 산화적 스트레스에 대한 생체 방어 기작의 일종인 SOD 함량의 증가, oxidized GSH/총 GSH 및 MDA 함량 감소를 나타냄에 따라 산화적 스트레스에 대한 우수한 항산화효과가 긍정적인 영향을 미친 것으로 판단된다. 또한, 뇌조직으로부터 분리한 미토콘드리아에 대하여 막 전위(MMP) 보호 및 ATP 함량 증가를 나타냈으며, 미토콘드리아와 관련된 apoptosis 경로에서 BAX의 감소 및 cytochrome c 방출 억제를 통해 caspase 3/7의 활성을 억제하는 것으로도 나타났다. 결국, 양파 과육 분획물(EOF)과 과피 분획물(EOP)은 AChE의 활성 억제 및 ACh의 함량을 증가시킴으로써 효과적인 콜린성 시스템 보호효과를 나타냄에 따라, Aβ로 유도된 인지기능 장애를 예방할 수 있는 고부가가치 건강기능식품 소재로의 활용 가능성이 기대된다.

• Biomolecules & Therapeutics
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• 제25권3호
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• pp.249-258
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• 2017

To examine the effect of biflorin, a component of Syzygium aromaticum, on memory deficit, we introduced a scopolamine-induced cognitive deficit mouse model. A single administration of biflorin increased latency time in the passive avoidance task, ameliorated alternation behavior in the Y-maze, and increased exploration time in the Morris water maze task, indicating the improvement of cognitive behaviors against cholinergic dysfunction. The biflorin-induced reverse of latency in the scopolamine-treated group was attenuated by MK-801, an NMDA receptor antagonist. Biflorin also enhanced cognitive function in a naïve mouse model. To understand the mechanism of biflorin for memory amelioration, we performed Western blot. Biflorin increased the activation of protein kinase C-${\zeta}$ and its downstream signaling molecules in the hippocampus. These results suggest that biflorin ameliorates drug-induced memory impairment by modulation of protein kinase C-${\zeta}$ signaling in mice, implying that biflorin could function as a possible therapeutic agent for the treatment of cognitive problems.

• Laboraroty Animal Research
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• 제34권4호
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• pp.317-328
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• 2018

Cognitive impairment responses are important research topics in the study of degenerative brain diseases as well as in understanding of human mental activities. To compare response to scopolamine (SPL)-induced cognitive impairment, we measured altered parameters for learning and memory ability, inflammatory response, oxidative stress, cholinergic dysfunction and neuronal cell damages, in Korl:ICR stock and two commercial breeder stocks (A:ICR and B:ICR) after relevant SPL exposure. In the water maze test, Korl:ICR showed no significant difference in SPL-induced learning and memory impairment compared to the two different ICRs, although escape latency was increased after SPL exposure. Although behavioral assessment using the manual avoidance test revealed reduced latency in all ICR mice after SPL treatment as compared to Vehicle, no differences were observed between the three ICR stocks. To determine cholinergic dysfunction induction by SPL exposure, activity of acetylcholinesterase (AChE) assessed in the three ICR stocks revealed no difference of acetylcholinesterase activity. Furthermore, low levels of superoxide dismutase (SOD) activity and high levels of inflammatory cytokines in SPL-treated group were maintained in all three ICR stocks, although some variations were observed between the SPL-treated groups. Neuronal cell damages induced by SPL showed similar response in all three ICR stocks, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, Nissl staining analysis and expression analyses of apoptosis-related proteins. Thus, the results of this study provide strong evidence that Korl:ICR is similar to the other two ICR. Stocks in response to learning and memory capacity.

• Biomolecules & Therapeutics
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• 제21권4호
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• pp.299-306
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• 2013

In the present study, we investigated the effect of ethanolic extract of the seed of Zizyphus jujuba var. spinosa (EEZS) on cholinergic blockade-induced memory impairment in mice. Male ICR mice were treated with EEZS. The behavioral tests were conducted using the passive avoidance, the Y-maze, and the Morris water maze tasks. EEZS (100 or 200 mg/kg, p.o.) significantly ameliorated the scopolamine-induced cognitive impairment in our present behavioral tasks without changes of locomotor activity. The ameliorating effect of EEZS on scopolamine-induced memory impairment was significantly reversed by a sub-effective dose of MK-801 (0.0125 mg/kg, s.c.). In addition, single administration of EEZS in normal naive mouse enhanced latency time in the passive avoidance task. Western blot analysis was employed to confirm the mechanism of memory-ameliorating effect of EEZS. Administration of EEZS (200 mg/kg) increased the level of memory-related signaling molecules, including phosphorylation of extracellular signal-regulated kinase or cAMP response element-binding protein in the hippocampal region. Also, the time-dependent expression level of brain-derived neurotrophic factor by the administration of EEZS was markedly increased from 3 to 9 h. These results suggest that EEZS has memory-ameliorating effect on scopolamine-induced cognitive impairment, which is mediated by the enhancement of the cholinergic neurotransmitter system, in part, via NMDA receptor signaling, and that EEZS would be useful agent against cognitive dysfunction such as Alzheimer's disease.

• 대한수의학회지
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• 제43권3호
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• pp.415-421
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• 2003

It is now generally accepted that acupuncture is effective in diarrhea caused by bacterial infection. However, its effect on the intestinal smooth muscle dysfunction is not clear. Therefore, we investigated the effect of acupuncture therapy at Jiao-chao (GV-1) on the intestinal muscle dysfunction in weaning piglets orally infected by Escherichia coli. The animals are divided into four groups; 1) E. coli + no-treatment, 2) E. coli + antibiotic, 3) E. coli + acupuncture, 4) normal group. In the three E. coli infected groups, low frequency electrical field stimulation (EFS, 1 Hz) provoked triphasic responses composed of initial relaxation followed by on-contraction and off-contraction. While in the normal group, EFS (1Hz) induced biphasic responses composed of relaxation during the stimulation and off-contraction. At the high frequency (16Hz) EFS, both on-contraction and off-contraction of the E. coli + antibiotic, E. coli + acupuncture and the normal group were larger than those of the E. coli + no-treatment group. In the non-adrenergic non-cholinergic (NANC) condition, only biphasic responses occurred to EFS in all experimental groups and the off-contraction of E. coli + antibiotic, E. coli + acupuncture and the normal group were larger than those of the E. coli + no-treatment group. The response to carbachol of those three groups was also significantly greater than that of the E. coli + no-treatment group. These results suggest that acupuncture is as effective as antibiotic in the dysfunction of colonic circular muscle caused by E. coli infection. The maintenance of contractile neuromuscular transmission seems to be involved in the mechanism of the acupuncture effects on diarrhea.

• The Korean Journal of Physiology and Pharmacology
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• 제21권6호
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• pp.657-666
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• 2017

Paclitaxel, a chemotherapeutic drug, induces severe peripheral neuropathy. Gabapentin (GBT) is a first line agent used to treat neuropathic pain, and its effect is mediated by spinal noradrenergic and muscarinic cholinergic receptors. Electro-acupuncture (EA) is used for treating various types of pain via its action through spinal opioidergic and noradrenergic receptors. Here, we investigated whether combined treatment of these two agents could exert a synergistic effect on paclitaxel-induced cold and mechanical allodynia, which were assessed by the acetone drop test and von Frey filament assay, respectively. Significant signs of allodynia were observed after four paclitaxel injections (a cumulative dose of 8 mg/kg, i.p.). GBT (3, 30, and 100 mg/kg, i.p.) or EA (ST36, Zusanli) alone produced dose-dependent anti-allodynic effects. The medium and highest doses of GBT (30 and 100 mg/kg) provided a strong analgesic effect, but they induced motor dysfunction in Rota-rod tests. On the contrary, the lowest dose of GBT (3 mg/kg) did not induce motor weakness, but it provided a brief analgesic effect. The combination of the lowest dose of GBT and EA resulted in a greater and longer effect, without inducing motor dysfunction. This effect on mechanical allodynia was blocked by spinal opioidergic (naloxone, $20{\mu}g$), or noradrenergic (idazoxan, $10{\mu}g$) receptor antagonist, whereas on cold allodynia, only opioidergic receptor antagonist blocked the effect. In conclusion, the combination of the lowest dose of GBT and EA has a robust and enduring analgesic action against paclitaxel-induced neuropathic pain, and it should be considered as an alternative treatment method.

• 한국약용작물학회지
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• 제25권6호
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• pp.353-360
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• 2017

Background: A critical features of Alzheimer's disease (AD) is cognitive dysfunction, which partly arises from decreased in acetylcholine levels. AD afftected brains are characterized by extensive oxidative stress, which is thought to be primarily induced by the amyloid beta ($A{\beta}$) peptide. In a previous study, Cinnamomum loureiroi tincture inhibited acetylcholinesterase (AchE) activity. That study identified AChE inhibitor in the C. loureiroi extract. Furthermore, the C. loureiroi extract enhanced memory in a trimethyltin (TMT)-induced model of cognitive dysfunction, as assessed via two behavioral tests. Rosa laevigata extract protected against oxidative stress-induced cytotoxicity. Administrating R. laevigata extracts to mice significantly reversed $A{\beta}$-induced learning and memory impairment, as shown in behavioral tests. Methods and Results: We conducted behavioral to examine the synergistic effects of C. loureiroi and R. laevigata extracts in inhibiting AChE and counteracting TMT-induced learning and memory losses. We also performed biochemical assays. The biochemical results showed a relationship between increased oxidative stress and cholinergic neurons damage in TMT-treated mice. Conclusions: A diet containing C. loureiroi and R. laevigata extracts ameliorated learning and memory impairments in the Y-maze and passive avoidance tests, and exerted synergistic inhibitory effect against AChE and lipid peroxidation.

• 대한임상독성학회지
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• 제11권1호
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• pp.31-35
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• 2013

Acute organophosphate intoxication is important because of its high morbidity and mortality. The mortality is still high despite the use of atropine as specific antidotal therapy and oximes for reactivation of acetylcholinesterase. Inhibition of acetylcholinesterase by organophosphate can cause acute parasympathetic system dysfunction, muscle weakness, seizure, coma, and respiratory failure. Acute alteration in conscious state or a coma, which may occur following organophosphate intoxication, is an indication of severe intoxication and poorer prognosis. This acute decline in conscious state often reverses when the cholinergic crisis settles; however, it may be prolonged in some patients. We report on a case of a 60-year-old male who showed prolonged decline in conscious state due to of Central Nervous System (CNS) toxicity after a suicide attempt with organophosphate.

• 생약학회지
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• 제41권3호
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• pp.196-203
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• 2010

Black sesame (Sesami semen nigrum) has been used to treat dizziness, earnoise, constipation in the traditional Chinese medicine. In the present study, we assessed memory enhancing properties of 70% ethanolic extract of black sesame (EBS70) and its ameliorating activities on learning and memory impairments induced by scopolamine. Drug-induced amnesia was made by scopolamine treatment (1 mg/kg, i.p.). Single EBS70 (200 mg/kg, p.o.) administration significantly enhanced cognitive function and attenuated scopolamine-induced cognitive impairments as determined by the passive avoidance and Y-maze tasks (P<0.05) and also reduced escape-latency on the Morris water maze task (P<0.05). In addition, EBS70 increased BDNF expression in hippocampus 4 h after its administration (P<0.05). These results suggest that EBS70 enhances learning and memory in normal state and attenuates amnesic state caused by cholinergic dysfunction.

• 동의신경정신과학회지
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• 제22권4호
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• pp.185-199
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• 2011

In the present study, we assessed the effect of the PPA (Polygala japonica Houtt., Polygala tenuifolia WILLD. and Acorus gramineus SOLAND. mixed preparation), a traditional herbal prescription, on the learning and memory impairments induced by scopolamine. The cognition-enhancing effect of PPA was investigated using a passive avoidance test, Y-maze test and the Morris water maze test in mice. Drug-induced amnesia was induced by treating animals with scopolamine (1 mg/kg, i.p.). A single PPA (400 and 800 (mg/kg)) administration significantly reversed the scopolamine-induced cognitive impairments in the passive avoidance test (P<0.05). On the Y-maze test, PPA (400 and 800 (mg/kg)) also significantly reversed scopolamine-induced cognitive impairments in mice (P<0.05). PPA also improved escape latencies in training trials and increased swimming times and distances within the target zone of the Morris water maze (P<0.05). These results suggest that PPA attenuates amnesic state induced by scopolamine and that these Effect are mediated by enhancing the cholinergic dysfunction.