• 한국한의학연구원논문집
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• 제8권1호
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• pp.109-126
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• 2002

The herbal extract (YMT_02) is a modified herbal extracts from Yukmijihwangtang (YMJ) to promote memory-enhancing. The YMJ extracts has been widely used as an anti-aging herbal medicine for hundred years in Asian countries. The purpose of this study is to; 1) quantitatively evaluate the memory-enhancing effect of YMT_02 by hehavior task, 2) identify candidate genes responsible for enhancing memory by cDNA microarray and 3) assess the anti-oxidant effect of YMT_02 on PC12 cell. Memory retention abilities are addressed by passive avoidance task with Sprague-Dawley (SD) male rat. Before the training session, the rats are subdivided into four groups and administrated with YMT_02, Ginkgo biloba, Soya lecithin and normal saline for 10 days. The retention test was performed. 24 hours after the training session. The retention time of the YMT_02 group was significantly (p<0.05) delayed $({\sim}100%)$, whereas Ginkgo biloba and Soya lecithin treatment delayed 20% and 10% respectively. The hippocampi of YMT_02 and control group were dissected and mRNA was further purified. After synthesizing cDNA using oligo-dT primer, the cDNA were applied and mRNA was further purified. After synthesizing cDNA using oligo-dT primer, the cDNA were applied to Incyte rat GEMTM 2 cDNA microarray. The microarray results show that prealbumin(transthyretin), phosphotidy lethanolamine N-methyltransferase, and PEP-19 are expressed abundantly in the YMT_02 treated group. Especially, PEP-19 is a neuron-specific protein, which inhibits apoptotic processes in neuronal cell. On the other hand, transcripts of RAB15, glutamate receptor subunit 2 and CDK 108 are abundant in control group. Besides, neuronal genes involved in neuronal death or neurodegeneration such as neuronal-pentraxin and spectrin are abundantly expressed in control group. Additionally, the YMT_02 shows an anti oxidative effect in the PC12 cell. The list of differentially expressed genes may implicate further insight on the action and mechanism behind the memory-enhancing effect of herbal extracts YMT_02, for example, anti-apoptotic, anti-oxidative, and neuroprotective effects.

• 동의신경정신과학회지
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• 제16권1호
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• pp.119-128
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• 2005

Objective : The purpose of this study was to estimate the effects of Ramulus et Uncus Uncariae DM fraction on memory enhancing in rats Methods : We oral administered Ramulus et Uncus Uncariae DM fraction to rats then executed passive avoidance test and observed figure of pyramidal neuron on CA1 Results : Findings from our experiments have shown that REUD(>1mg/100g/ml) was effective in memorial improvement. and oral administration of REUD(100mg/100g/ml) for 2 weeks was found to induced the figure of pyramidal neuron on CA1 in rat hippocampus injured by scopolamine. Conclusions : As the result of this study, Decrease of memory induced by injection of scopolamine into rat was also attenuted by REUD, based on passive avoidance test, and REUD was found to reduce the activity of AChE and induced about the CA1 in rat hippocampus. Base on these findings, REUD may be beneficial for the treatment of AD.

• Journal of Microbiology and Biotechnology
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• 제23권12호
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• pp.1779-1784
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• 2013

Although enzyme-hydrolyzed silk fibroin has been reported to enhance cognitive function before, it has been still unknown which peptides can improve memory. Here we report that amino acid sequences of three novel peptides were identified from fibroin hydrolysate. Fibroin hydrolysate was obtained by hydrolysis with protease after partial hydrolysis with 5M $CaCl_2$. Synthesized peptides derived from these sequences improved scopolamine-induced memory impairments in mice. We confirmed this hydrolysate had effects that improved learning and memory abilities by performing the Rey-Kim test. From this hydrolysate of silk fibroin, amino acid sequences of eight peptides were identified by LC-MS/MS. Three peptides (GAGAGTGSSGFGPY, GAGAGSGAGSGAGAGSGAGAGY, and SGAGSGAGAGSGAGAGSGA) were synthesized to investigate whether they could improve memory. Passive avoidance test and Morris water maze test were performed, and all peptides showed memory-enhancing abilities on scopolamine-induced memory impairments in mice. In this study, we identified three novel peptides that could improve memory, and that silk fibroin hydrolysate was a mixture of various active peptides that could enhance memory.

• Journal of Korean Neurosurgical Society
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• 제66권5호
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• pp.511-524
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• 2023

Objective : This animal model aimed to compare the rat group that received brain irradiation and did not receive additional treatment (only saline) and the rat group that underwent brain irradiation and received Granulocyte colony stimulating factor (G-CSF) treatment. In addition, the effects of G-CSF on brain functions were examined by magnetic resonance (MR) imaging and histopathologically. Methods : This study used 24 female Wistar albino rats. Drug administration (saline or G-CSF) was started at the beginning of the study and continued for 15 days after whole-brain radiotherapy (WBRT). WBRT was given on day 7 of the start of the study. At the end of 15 days, the behavioral tests, including the three-chamber sociability test, open field test, and passive avoidance learning test, were done. After the behavioral test, the animals performed the MR spectroscopy procedure. At the end of the study, cervical dislocation was applied to all animals. Results : G-CSF treatment positively affected the results of the three-chamber sociability test, open-space test and passive avoidance learning test, cornu Ammonis (CA) 1, CA3, and Purkinje neuron counts, and the brain levels of brain-derived neurotrophic factor and postsynaptic density protein-95. However, G-CSF treatment reduced the glial fibrillary acidic protein immunostaining index and brain levels of malondialdehyde, tumor necrosis factor-alpha, nuclear factor kappa-B, and lactate. In addition, on MR spectroscopy, G-CSF had a reversible effect on brain lactate levels. Conclusion : In this first designed brain irradiation animal model, which evaluated G-CSF effects, we observed that G-CSF had reparative, neuroprotective and anti-neurodegenerative effects and had increased neurotrophic factor expression, neuronal counts, and morphology changes. In addition, G-CSF had a proven lactate-lowering effect in MR spectroscopy and brain materials.

• Food Science and Biotechnology
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• 제17권3호
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• pp.594-597
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• 2008

Natural products have been used to treat many neurological illnesses such as Alzheimer's disease. In the present study, the effects of the water extract of smoke-dried skipjack tuna (WSST), which is used as a traditional seasoning in Japan, as well as its fractions on acetylcholinesterase (AChE) inhibition in vitro and on memory in scopolamine-induced amnesia mice in vivo were evaluated. Bio-Rad P-2 gel permeation chromatography revealed the presence of 7 peaks and AChE significantly inhibited peak 3 and 5. When in vivo behavioral studies were conducted, a passive avoidance test revealed that treatment with 50 and 100 mg/kg WSST as well as with fraction 3 and 5 improved the loss in memory retention induced by scopolamine. These results suggest that skipjack tuna extract and its fractions improve memory deficits and that these substances are suitable for use in healthy foods designed to improve memory deficits induced by aging and Alzheimer's disease.

• Natural Product Sciences
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• 제22권4호
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• pp.299-306
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• 2016

This study aimed to establish the quantitative method to analyze the content of peroxynitrite-scavengers belonging to polyphenols in six Korean Quercus species (Quercus mongolica, Q. dentata, Q. acutissima, Q. alienta, Q. serrata, and Q. variabilis) by HPLC. The twelve peroxynitrite-scavengers, flavanols (catechins: (+)-catechin, (-)-epicatechin, and (-)-epigallocatechin), flavonols (kaempferol and quercetin), flavonol glycosides (astragalin, quercitrin, and isoquercitrin), flavonol acylated glycosides (astragalin 6''-gallate and isoquercitrin 6''-gallate), gallic acid and its dimer (ellagic acid) were analyzed by HPLC. Further, anti-Alzheimer's activity was assayed in a passive avoidance testusing mice by measuring the retention latency (sec), the concentration of acetylcholine (ACh), and acetylcholinesterase (AChE) activity. Simultaneous analysis of the extracts of the six Quercus leaves was achieved on a Capcell C18 column ($5{\mu}m$, $250mm{\times}4.6mm\;i.d.$) with a gradient elution of 0.05% HAc and 0.05% HAc in $CH_3CN$. In the extract of Q. mongolica leaves, the content of gallic acid (32.53 mg/g), (+)-catechin (28.78 mg/g), (-)-epicatehin (22.03 mg/g), astragalin 6''-gallate (20.94 mg/g), and isoquercitrin 6''-gallate (44.11 mg/g) and peroxynitrite-scavenging activity ($IC_{50}$, $0.831{\mu}g/ml$) were high. This extract delayed the retention latency and inhibited acetylcholinesterase activity in scopolamine-induced memory impairment of mice, suggesting that it has anti-Alzheimer's activity.

• Journal of Ginseng Research
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• 제31권1호
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• pp.44-50
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• 2007

Ginseng powerfully tonifies the original Qi. Ginseng used for insomnia, palpitations with anxiety, restlessness from deficient Qi and blood and mental disorientation. In order to investigate whether Ginseng cerebral ischemia-induced neuronal and cognitive impairments, we examined the effect of Ginseng on ischemia-induced cell death in the hippocampus, and on the impaired learning and memory in the Morris water maze and passive avoidance in rats. Ginseng when administered to rat at a dose of 200 mg/kg i.p. water extracts to 0 minutes and 90 minutes after 4-VO, significantly neuroprotective effects by 86.4% in the hippocampus of treated rats. For behavior test, rats were administered Ginseng (200mg/kg p.o.) daily for two weeks, followed by their training to the tasks. Treatment with Ginseng produced a marked improvement in escape latency to find the platform in the Morris water maze. Ginseng reduced the ischemia-induced learning disability in the passive avoidance. Consistent with behavioral data, treatments with Ginseng reduced jschemia-induced cell death in the hippocampal CA1 area. Oxidative stress is a causal factor in the neuropathogenesis of ischemic-reperfusion injury. Oxidative stress was examined in a rat model of global brain ischemia. The effects of Ginseng on lipid peroxidation (inhibition of the production of malondialdehyde, MDA) in different regions of the rat brain were studied. Ferrous sulfate and ascorbic acid (FeAs) were used to induce lipid peroxidation. The antiperoxidative effect showed 48-72% protection from tissue damage as compared with untreated animals. These results showed that Ginseng have a protective effect against ischemia-induced neuronal loss and learning and memory damage.

• 한국식품영양학회지
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• 제29권3호
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• pp.382-391
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• 2016

인지기능 활성을 가진 생약복합물을 선정하여 최적조성물을 조제한 다음, 생약복합물의 첨가비율을 달리하여 치매유도 동물모델에서 항산화 효과와 인지기능 개선을 확인한 결과는 다음과 같다. 1. 20일간 사육한 흰쥐 혈청의 GOT, GPT, creatinine 및 BUN 활성을 측정한 결과, 생약복합물을 투여한 군(3, 4군)이 정상군(1군)에 비해 GOT 농도는 감소하였고, GPT 농도와 Creatinine 농도는 유의적인 차이는 없었다. BUN 농도는 정상군(1군)에 비해 생약복합물을 투여한 군(3, 4군)이 유의적으로 감소하였다. 2. 혈액 중의 총 콜레스테롤과 HDL-cholesterol은 유의적인 차이가 없었으나, 중성지방은 전군에서 정상군(1군)에 비해 치매유발군인 2군이 낮았고, 생약복합물 투여군(3, 4군), 치매치료군(5군)은 가장 낮았으며, 이들 군 간에는 유의적인 차이는 없었다. 3. 혈액 SOD 활성은 정상군(1군), TMT 투여군(2군) 및 tacrine 투여군(5군) 간에는 유의적인 차이가 없었으나, 생약복합물 투여군(3, 4군)이 다소 높아 유의적인 차이를 나타내었다(p<0.05). MDA 함량은 정상군인 1군과 치매치료군인 5군이 치매유발군인 2군과 생약복합물 투여군(3, 4군)에 비해 유의적으로 높았으며, 2, 3, 4군 간에는 유의적인 차이가 없었다. 4. AChE 활성은 TMT로 치매를 유발한 2군이 가장 높았으며, 치매치료군(5군)은 정상군(1군)의 수준으로 가장 낮게 나타났다. 그리고 생약복합물을 투여한 3군, 4군에서는 유의적 차이는 없으나, TMT로 치매를 유발한 2군보다는 유의적으로 감소하였고(p<0.05), 치매치료군인 5군보다는 다소 높게 나타났다. 5. 단기기억능력을 시험하기 위한 Y-maze를 실시한 결과는 Y-maze의 각 arm을 통과한 총 횟수는 전군에서 유의적인 차이는 없었다. 교차행동력은 TMT 투여군인 2군이 가장 낮았으며, 치매치료제인 tacrine을 투여한 5군이 가장 높아 5군(tacrine 투여)은 TMT 투여군인 2군에 비해 약 125% 현저한 기억력 증가를 보였다. 이에 반해 생약복합물 투여한 2, 3군은 정상군과 유의적인 차이가 없었으나, TMT 투여군인 2군에 비해 각각 117.32%와 120.38% 수준으로 기억력 증가를 보였다. 장기기억능력을 시험하기 위한 수동회피실험의 결과, TMT 투여군(2군)은 전군에서 가장 낮았으나, 생약복합물 중, 고용량 투여군(3, 4군) 및 tacrine 투여군은 증가하였고, 특히 고용량(4군)에서 유의성 있는 증가를 나타내어(p<0.05) 정상군에 가깝게 회복시켜 주는 경향을 보여 주었다. 이상의 결과를 통하여 생약복합물은 치매 유발 동물모델의 항산화능의 저하를 억제하고, AChE 활성을 억제하여 ACh의 활성을 촉진하므로 장 단기 기억능력의 회복 및 개선효과를 확인할 수 있었다. 그러나 향후 생약복합물의 농도에 따른 첨가군을 확대하여 인지기능 개선에 가장 효과적인 최적농도를 도출하는 연구가 계속 진행되어야 할 것으로 사료된다.

• 한국식품과학회지
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• 제48권3호
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• pp.275-283
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• 2016

본 연구는 스트렙토조토신에 의해 당뇨가 유발된 기억력 감퇴 모델에서 황칠나무 잎 열수추출물(DMW)의 학습 및 기억력 개선 효과를 평가하기 위해 수행되어졌다. 6주령의 SD-래트를 총 5개 군으로 분리 하였고, 11주간 24시간 간격으로 DMW를 100과 300 mg/kg b.w.농도로 경구 투여 하였으며, 양성대조군으로 donepezil (1 mg/kg b.w.)을 처리하였다. 7일 간격으로 체중과 혈당을 측정하였으며 STZ군에 비해 DMW군에서 유의한 체중 증가를 확인 할 수 있었다. 혈당 측정 결과 DMW군에서 6주째부터 혈당이 감소하기 시작하였으며, STZ군에 비해 유의적인 혈당 감소를 나타내었다. 혈청 내 바이오마커 측정 결과 혈중 포도당은 DMW 시료군에서 유의하게 감소하였고, 인슐린 호르몬 농도와 혈액 요소질소 또한 유의한 감소를 나타내었다. 간 기능 수치와 TG, TC, 그리고 크레아틴 농도에서는 각 군 간의 유의적 차이는 확인할 수 없었다. Morris water maze test와 passive avoidance test를 통해 STZ로 유도한 당뇨 모델에서 학습 및 기억력 장애를 확인 하였으며, DMW를 투여함으로서 학습 및 기억력이 유의적으로 회복, 증가한 것을 확인할 수 있었다. 또한 뇌 해마에서 Ach 함량과 AchE 활성 측정 결과, 당뇨 대조군에 비해 Ach 함량은 증가하였으며, AchE의 활성은 유의적으로 감소 한 것을 확인 하였다. 본 연구 결과로 STZ로 유도된 고 혈당 동물모델에서 황칠나무 잎 열수추출물(DMW)의 당뇨 개선 및 학습, 기억력 개선 효과를 확인 할 수 있었다. 이는 당뇨의 개선 효과와 더불어 고 혈당으로 인한 퇴행성 치매의 예방과 치료에도 일부 효과적일 것으로 사료된다. 이러한 연구 결과를 바탕으로 황칠 열수추출물(DMW)이 당뇨에 의한 학습 및 기억력의 저하에 있어 효과적인 대안으로서 보다 더 넓은 분야에서 연구되기를 바라는 바이다.

• 한국식품영양과학회지
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• 제41권2호
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• pp.192-196
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• 2012

현재까지 복분자가 인지능력 및 기억력에 미치는 영향에 대해 연구된 바가 없다. 본 연구에서는 복분자 물추출물이 기억력에 미치는 영향을 조사하기 위해 복분자 물추출물을 100 mg/kg body weight/day로 4주간 투여한 후 스코폴라민(1 mg/kg body weight)을 복강 주사하여 기억력 감퇴를 유발한 후 수동회피시험과 수중미로시험을 실시하여 복분자물추출물의 기억력 개선 효과를 평가하였다. 수동회피실험에서 스코폴라민으로 기억력 감퇴를 유도한 경우 밝은 방에서의 체류시간이 현저히 짧아졌고 복분자 물추출물을 섭취한 군에서는 밝은 방에서의 체류 시간이 스코폴라민 투여군에 비해 현저히 증가하였다. 또한 수중미로시험에서도 스코폴라민 투여군의 도피대를 찾아가는 탈출잠복기가 정상대조군에 비해 현저히 증가하였고 복분자 물추출물 투여군에서는 스코폴라민 군에 비해 탈출잠복기가 유의적으로 감소하였다. 대뇌피질에서 기억력에서 중요한 역할을 하는 acetylcholinesterase활성은 스코폴라민에 의해 증가하고, 복분자 물추출물에 의해 감소하였다. 이상의 결과는 복분자 물추출물이 항콜린제인 스코폴라민에 의해 유도된 기억력 감퇴를 효과적으로 개선함을 보여주며, 이는 acetylcholinesterase의 활성을 저해함으로써 이루어짐을 나타낸다. 향후 더 많은 연구가 필요하나 본 연구는 복분자 물추출물을 기억력 개선 또는 증강제로 개발할 수 있는 가능성을 제시한다.