• 대한한의학회지
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• 제35권4호
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• pp.10-23
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• 2014

Objectives: This study evaluated the effects of Guibi-tang (GBT) on neuronal apoptosis and cognitive impairment induced by beta amyloid ($A{\beta}$), (1-42) injection in the hippocampus of ICR mice. Methods: $A{\beta}$ (1-42) was injected unilaterally into the lateral ventricle using a Hamilton syringe and micropump ($2{\mu}g/3{\mu}{\ell}$, $0.6{\mu}{\ell}/min$). Water extract of GBT was administered orally once a day (500 mg/kg) for 3 weeks after the $A{\beta}$ (1-42) injection. Acquisition of learning and retention of memory were tested using the Morris water maze. Neuronal damage and $A{\beta}$ accumulation in the hippocampus was observed using cresyl violet and Congo red staining. The anti-apoptotic effect of GBT was evaluated using TUNEL labeling in the hippocampus. Results: GBT significantly shortened the escape latencies during acquisition training trials. GBT significantly increased the number of target headings to the platform site, the swimming time spent in the target quadrant, and significantly shortened the time for the 1st target heading during the retention test trial. GBT significantly attenuated the reduction in thickness and number of CA1 neurons, and $A{\beta}$ accumulation in the hippocampus produced by $A{\beta}$ (1-42) injection. GBT significantly reduced the number of TUNEL-labeled neurons in the hippocampus. Conclusion: These results suggest that GBT improved cognitive impairment by reducing neuronal apoptosis and $A{\beta}$ accumulation in the hippocampus. GBT may be a beneficial herbal formulation in treating cognitive impairment including Alzheimer's disease.

• 한국식품영양과학회지
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• 제42권8호
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• pp.1190-1196
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• 2013

연구에서는 백삼이나 홍삼의 기억력 개선 효과 연구를 기초로 흑삼의 기억력 개선효과 여부를 판단하고자 scopolamine으로 유도된 시험동물에게 7주간 시료 물질(백삼, WG; 홍삼, RG; 흑삼, BG) 추출액을 투여한 후, 행동학적인 평가 및 뇌 조직 내 malondialdehyde 농도, ChAT 활성 변화를 비교 분석하여 기억력 및 학습능력 손상에 대한 개선효과를 알아보고자 하였다. 수동회피시험에서 BG군과 RG군의 latency time이 scopolamine 투여한 PC군(positive control)에 비해서 유의적으로 길어지는 결과를 나타냈다. 수중미로시험에서도 BG군과 RG군의 scopolamine에 의한 기억 손상이 유의적으로 개선되어 NC군의 escape latency 수준 정도로 낮아짐을 확인할 수 있었다. 또한 probe test에서도 BG군과 RG군에서 장기 기억력 손상이 유의적으로 개선됨이 확인되었다. BG군과 RG군의 뇌조직 ChAT 효소 활성은 PC군에 비해 각각 42%, 71% 수준의 유의성 있는 활성증가를 보였다. 지질 과산화도 malondialdehyde 측정 결과에서 PC군 대비 RG군과 BG군에서 각각 37%, 33% 수준의 유의성 있는 감소를 보였다. 이상의 결과를 요약하면 시험물질 가운데 흑삼의 반복 경구투여는 scopolamine으로 유도된 흰쥐에서 기억력 감퇴를 개선하는 데 가장 효과적인 것으로 사료된다.

• 대한한의학방제학회지
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• 제25권1호
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• pp.69-87
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• 2017

Objectives : Cheongnoemyeongsin-hwan (CNMSH) is a herb medicine to treat cognitive impairment. This study was investigated the effects of CNMSH on learning and memory impairment induced by cerebral hypoperfusion. Cerebral hypoperfusion was produced chronically by permanent bilateral common carotid artery occlusion (BCCAO) in rats. Methods : CNMSH was administered orally once a day (250 mg/kg) for 28 days starting at 4th week after the BCCAO. The acquisition of learning and the retention of memory were tested on 9th week after the BCCAO using the Morris water maze. In addition, effect of CNMSH on neuronal apoptosis and ${\beta}-amyloid$ accumulation in the hippocmapus was evaluated with immunohistochemistry and Western blotting. Results : 1. CNMSH and ChAL significantly shortened the escape latencies on the 2nd day of acquisition training trials. 2. ChAL significantly prolonged the swimming time spent in the target and peri-target zones and CNMSH also significantly prolonged the swimming time spent in the peri-target zone. 3. CNMSH and ChAL significantly increased the number of target heading in the retention test. 4. ChAL significantly shortened the time of the 1st target heading in the retention test, but CNMSH insignificantly shortened the time of that. 5. CNMSH and ChAL significantly increased the memory score in the retention test. 6. CNMSH and ChAL significantly attenuated the reduction of CA1 neurons, but insignificantly attenuated the reduction of CA1 thickness. 7. CNMSH and ChAL significantly attenuated the up-regulation of Bax expression in the CA1 of hippocampus. 8. CNMSH and ChAL significantly attenuated the up-regulation of cascapse-3 expression in the CA1 of hippocampus. 9. CNMSH and ChAL significantly attenuated the ${\beta}-amyloid$ accumulation in the CA1 of hippocampus. 10. CNMSH and ChAL significantly attenuated the up-regulation of APP expression in the CA1 of hippocampus. 11. CNMSH and ChAL significantly attenuated the up-regulation of BACE-1 expression in the CA1 of hippocampus. Conclusions : The results show that CNMSH attenuates neuronal apoptosis and ${\beta}-amyloid$ accumulation in the hippocampus and alleviates the impairment of learning and memory produced by chronic cerebral hypoperfusion. These results suggest that CNMSH may be a beneficial medicinal herb to treat cognitive impairment associated with neurodegenerative diseases.

• 동의신경정신과학회지
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• 제24권4호
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• pp.419-434
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• 2013

Objectives: The object of this study is to observe the cognition and motor function recovery effects of Joojakwhan (JJW), a traditional Korean poly-herbal formula for treating various neuropsychiatric diseases such as dementia, for the mildly stroke rats, with 60 minutes of reperfusion transient middle cerebral artery occlusion (tMCAO). Methods: In the present study, 125, 250 and 500 mg/kg of JJW were orally administered, once per day for 10 continuous days 2 hours after the tMCAO. The body weight changes, infarct sizes under 2% 2, 3, 5-triphenyl tetrazolium chloride (TTC) stain, sensorimotor functions and cognitive motor behavior tests were serially monitored with cerebral caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP)-immunoreactivities and histopathological changes. The effects of tMCAO on sensorimotor functions were evaluated by using of limb placing and body-swing tests, and the cognitive motor behaviors were also observed with water maze tests. Results: From the results of tMCAO, with marked decreases of body weights, disorders of sensorimotor functions increases the limb placing test scores, and decrease the numbers and percentages of body swings to the ipsilateral sides. The cognitive motor behaviors increases the distances and time to reach the escape platform which included the inhibitions of the decreases with repeated trials that were observed with focal cerebral cortex infarct volumes. In addition, the marked increases of the atrophy, numbers of degeneration, caspase-3- and PARP-immunoreactive cells around peri-infarct ipsilateral cerebral cortex were also observed in tMCAO controls when compared with the sham control rats, respectively. Conclusions: The results obtained from this study suggest that oral administrations of JJW indicate obvious cognitions and motor function recoveries of the rats with tMCAO, mild strokes, which are mediated by neuro-protective effects through known antioxidant effects of components.

• 한국자원식물학회지
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• 제26권4호
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• pp.417-425
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• 2013

본 연구에서는 도라지 추출물에 대한 세포 독성을 확인하였으며, $A{\beta}$에 의한 PC12 세포 독성에 대한 보호효과를 관찰하였다. 또한 도라지 추출물과 도라지 추출물 연양갱을 4주간 강제 경구 투여하여 Morris 수중미로시험에서 도달지점까지의 도달시간이 도라지 추출물 및 도라지 추출물 연양갱 투여에 의해서 모두에서 유의하게 감소하였다. 이와 유사하게 수동회피시험에서도 자극이 있는 어두운 방을 나오는 시간이 도라지 추출물 및 도라지 추출물 연양갱 투여에 의해서 현저하게 감소하였다. 따라서 도라지 추출물 및 도라지 추출물 연양갱은 인지능 개선에 도움을 줄 것으로 생각된다.

• Journal of Ginseng Research
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• 제39권2호
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• pp.116-124
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• 2015

Background: Ginseng, the root of Panax ginseng (PG), is used widely as a herbal medicine to prevent and treat various diseases. Panax ginseng has pharmacological effects on neurodegenerative diseases such as Alzheimer's disease (AD). The present study evaluated the neuroprotective effects of PG and its possible neuroprotective mechanisms in advanced glycation end product (AGE)-induced AD in a rat model. Methods: Advanced glycation end products were injected bilaterally into the CA3 region of the rats' brains. The Morris water maze test and step-down type passive avoidance test were performed to evaluate their memory and cognitive abilities. The oxidation indexes in the hippocampus were detected. Immunohistochemistry was conducted to visualize the receptors for advanced glycation end products (RAGEs) and nuclear factor-kappa-light-chain-enhancer of activated B cell (NF-${\kappa}B$). Results: Behavioral results showed that PG (1 g/kg, 0.5 g/kg, and 0.25 g/kg) significantly shortened the escape latency, remarkably increased the number of crossing times, significantly decreased the number of errors, and prolonged the latency in rats with AGE-induced AD. Panax ginseng also significantly reduced the malondialdehyde level, increased the glutathione content, and increased superoxide dismutase activity in the hippocampus. Panax ginseng significantly decreased the expression of RAGE and NF-${\kappa}B$. The blockade of anti-RAGE antibody could significantly reduce AGE-induced impairments and regulate these expressions. Conclusion: Our results demonstrated that PG significantly inhibits AGE-induced memory impairment and attenuates Alzheimer-like pathophysiological changes. These neuroprotective effects of PG may be associated with the RAGE/NF-${\kappa}B$ pathway. Our results provided the experimental basis for applying PG in preventing and treating AD.

• Nutrition Research and Practice
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• 제12권3호
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• pp.199-207
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• 2018

BACKGROUND/OBJECTIVES: Fermented Laminaria japonica (FL), a type sea tangle used as a functional food ingredient, has been reported to possess cognitive improving properties that may aid in the treatment of common neurodegenerative disorders, such as dementia. MATERIALS/METHODS: We examined the effects of FL on scopolamine (Sco)- and ethanol (EtOH)-induced hippocampus-dependent memory impairment, using the Passive avoidance (PA) and Morris water maze (MWM) tests. To examine the underlying mechanisms associated with neuroprotective effects, we analyzed acetylcholine (ACh) and acetylcholinesterase (AChE) activity, brain tissue expression of muscarinic acetylcholine receptor (mAChR), cAMP response element binding protein (CREB) and extracellular signal-regulated kinases 1/2 (ERK1/2), and immunohistochemical analysis, in the hippocampus of mice, compared to current drug therapy intervention. Biochemical blood analysis was carried out to determine the effects of FL on alanine transaminase (ALT), aspartate transaminase (AST), and triglyceride (TG) and total cholesterol (TC) levels. 7 groups (n = 10) consisted of a control (CON), 3 Sco-induced dementia and 3 EtOH-induced dementia groups, with both dementia group types containing an untreated group (Sco and EtOH); a positive control, orally administered donepezil (Dpz) (4mg/kg) (Sco + Dpz and EtOH + Dpz); and an FL (50 mg/kg) treatment group (Sco + FL50 and EtOH + FL50), orally administered over the 4-week experimental period. RESULTS: FL50 significantly reduced EtOH-induced increase in AST and ALT levels. FL50 treatment reduced EtOH-impaired step-through latency time in the PA test, and Sco- and EtOH-induced dementia escape latency times in the MWM test. Moreover, anticholinergic effects of Sco and EtOH on the brain were reversed by FL50, through the attenuation of AChE activity and elevation of ACh concentration. FL50 elevated ERK1/2 protein expression and increased p-CREB (ser133) in hippocampus brain tissue, according to Western blot and immunohistochemistry analysis, respectively. CONCLUSION: Overall, these results suggest that FL may be considered an efficacious intervention for Sco- and EtOH-induced dementia, in terms of reversing cognitive impairment and neuroplastic dysfunction.

• 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.

• 한국응용과학기술학회지
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• 제37권3호
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• pp.418-428
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• 2020

본 연구는 알츠하이머(Alzheimer's disease: AD) 형질전환 생쥐를 대상으로 저항성 운동(resistance exercise: RE)이 해마의 베타 아밀로이드(β-amyloid: Aβ) 단백질 대사, 신경세포사멸 및 인지기능에 미치는 영향을 확인하는데 목적이 있다. AD 비 형질전환 생쥐(non-transgenic: non-tg, n=14)와 형질전환 생쥐(transgenic: Tg, n=14)를 무선 배정하여 비 형질전환 생쥐 대조군 (non-tg-control: NTC, n=7), 비 형질전환 생쥐 저항성 운동군(non-tg-RE: NTRE, n=7), 형질전환 대조군(tg-control: TC, n=7) 및 형질전환 저항성 운동군(tg-RE: TRE, n=7)으로 구분하였다. RE는 특수 제작한 사다리 저항성 운동 기구를 사용하여 점진적으로 set 수를 증가시켜 총 8주간 실시하였다. 운동 후 인지기능 능력을 평가하기 위한 수중미로검사와 Aβ 단백질 대사, 신경세포사멸 지표 및 SIRT1/PGC-1α 단백질 발현 수준을 확인하였다. 수중미로검사 결과 거리와 시간 모두 TC 집단에서 유의하게 증가 되었지만 RE를 실시한 TRE 집단에서 거리와 시간이 감소 되어 인지능력이 개선된 것으로 확인되었다. 또한, TC 집단에서 증가된 Aβ 단백질 발현은 RE를 통해 감소하는 것으로 나타났다. 신경세포사멸 관련 단백질인 Bcl-2/Bax ratio는 TC 집단에서 유의하게 감소되어 신경세포사멸이 증가 된 것으로 나타났지만 RE는 Bcl-2/Bax ratio을 증가시켜 신경세포사멸을 감소시킨 것으로 확인되었다. TC 집단에서 증가된 BACE1 및 ROCK1과 감소된 ADAM10과 RARβ 단백질 발현은 RE를 통해 감소되거나 증가 된 것으로 나타났고, SIRT1/PGC-1α 단백질 발현은 TC 집단에서 감소 되었지만 RE를 통해 증가 된 것으로 나타났다. 따라서 8주간의 RE는 AD의 병리학적 특징인 Aβ 단백질 발현을 감소시키고 관련 생성 기전들을 조절하여(SIRT1/PGC-1α 기전 활성, 아밀로이드 생성기전 억제, 비-아밀로이드 생성기전 활성) 신경세포사멸 억제시키고 결과적으로 인지기능을 개선 시킬 수 있는 효과적인 운동 방법이라고 생각된다.