• 동의생리병리학회지
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• 제25권3호
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• pp.406-416
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• 2011

In this study, we have verified the memory and cognitive enhancing effect of Longanae Arillus, the fruit of Euphoria longana Lamarck, which has been used as a tonic and for the treatment of amnesia, insomnia, and palpitations in oriental medicine. To investigate the effect of Longanae Arillus water extract(LAE) on the memory and cognitive dysfunction, scopolamine (1 mg/kg, i.p.) was injected in C57BL/6 mice and several behavior tests including Y-maze, Morris water-maze, passive avoidance and fear conditioning tests were conducted. Administration of LAE (100 or 200 mg/kg/day, p.o.) effectively improved scopolamine-induced memory impairment and dysfunction. To further determine the possible molecule mechanism of LAE, we have examined the activity and/or mRNA expression of diverse proteins involved in the acetylcholine metabolism. LAE particularly increased the amount of acetylcholine in the cortex which was mediated by suppression of acetylcholine esterase (AchE) activity. In addition, LAE elevated the mRNA expression of muscarinic acetylcholine receptors (mAchRs) without affecting the mRNA levels of choline acetyltransferase (ChAT) and acetylcholine esterase (AchE). In another experiment, LAE effectively inhibited mRNA expression of pro-inflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-$1{\beta}$ (IL1-${\beta}$), which seemed to be mediated by inhibition of upstream transcription factor NF-${\kappa}B$ and extracellular-regulated kinase 1/2 (ERK1/2). These results demonstrate that Longanae Arillus can increase acetylcholine amount the cortex via regulation of AchE activity as well as mAchRs expression and decrease pro-inflammatory responses via inhibition of NF-${\kappa}B$ signaling pathway, thereby having therapeutic potential to improve memory and cognitive deficit in amnesia.

• 동아시아식생활학회지
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• 제14권1호
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• pp.64-69
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• 2004

본 연구에서는 이미 항산화 효과로 알려져 있는 대두와 약성이 탁월한 약콩에서 AChE 활성 억제효과와 Free radical scavenger 효과를 노화로 인한 질병 예방효과에 대한 기초자료를 제공하고자 수행하였다. 1. 대두 열탕 추출물의 경우 저농도인 1, 0.1 mg/$m\ell$에서는AChE의 활성 억제 효과가 메탄을 추출물보다 높았다. (P<0.001) 2. 대두, 약콩 메탄올 추출물에서는 고농도인 5 mg/$m\ell$에서 각 시료의 효과가 62.0$\pm$2.43%, 65.0$\pm$3.29%로 비슷했으나 저농도인 0.1 mg/$m\ell$에서는 약콩의 경우 25.5$\pm$0.94%로 약콩이 대두에 비해 유의적인 AChE 억제효과를 나타냈다. (p<0.001) 3. 시간에 따른 Free radical scavenger효과는 비타민 C의 경우 시간에 따라 비슷한 효과를 보였으나 대두와 약콩은 incubating 시간에 따라 free radical 억제효과가 증가해 높은 항산화 효과를 볼 수 있었다. 4. 대두, 약콩 메탄올 추출물에서는 약콩이 고농도인 5mg/$m\ell$에서 약4배 정도의 효과를 보였으며 Free radical scavenger의 50%효과를 나타내는 $IC_{50}$/에서는 약 10배 정도로 높은 Free radical scavenger 효과를 나타내 약콩이 대두에 비해 유의적으로 높은 효과를 나타내었다. 결론적으로, 대두와 약콩의 추출물은 AChE 활성억제효과에 있어서 좋은 효과를 나타내며 또한 노화의 원인과 질병의 원인이 되는 free radical을 억제하는 효과를 가지고 있어 노인성 치매를 비롯하여 파킨슨씨병, 뇌허혈 및 뇌졸중과 같은 각종 노인성 질환예방에 도움이 될 것으로 보인다.

• Applied Biological Chemistry
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• 제49권4호
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• pp.315-321
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• 2006

유기인계나 카바메이트 살충제는 신경전달계 효소인 Acetylcholinesterase(AchE)를 저해하므로 농산물중에서 농약의 잔류여부 확인이 가능하다. 이러한 바이오센서는 환경 관리를 위한 민감한 센서로 사용될 수 있으며, 최근에는 AchE를 이용한 잔류농약을 측정할 수 있는 바이오센서 기술이 주목을 받고 있다. 우리는 최근에 감광성고분자물질인 고정화물질을 이용하여 광기교화반응에 의해 AchE를 막에 고정화시켜 잔류농약을 측정할 수 있는 바이오센서를 개발하였다. 고정화시킨 효소는 $4^{\circ}C$에서 6개월 동안 안정하였으며, 유기인계와 카바메이트계의 농약에 대한 반응에서도 기존의 용액형태의 효소보다 민감한 반응을 보였다. 또한 본 연구개발로 제작된 바이오센서에 의한 잔류농약 측정법은 용액형태의 효소에 의한 잔류농약 측정법보다 신속 간편하여 5분 안에 잔류농약에 대한 효소의 억제율을 측정할 수 있었으며, chlorpyrifos, cabaryl, carbofuran methidathion에 대해 농약의 검출 능력이 정밀분석법에 의한 검출한계에 근접한 것으로 나타났다

• 대한본초학회지
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• 제24권4호
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• pp.121-126
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• 2009

Objectives : To evaluate the radical scavenging and acetylcholinesterase (AChE) inhibitory activities of the ethylacetate (EtOAc)-soluble portion of a methanolic extract of Aster yomena, three different assay systems were performed. Methods : The antioxidant activity of A. yomena extract was tested as its capacity to scavenging free radicals of DPPH and $ABTS^+$, which has been widely used to evaluate the antioxidant activity of natural products from plant sources. AChE inhibitory activity was tested against mouse brain AChE by spectrophotometric method of Ellman using ELISA microplate reader. Results : The methanolic extract of A. yomena was fractionated and the EtOAc-soluble portion showed significant AChE inhibitory and free radical scavenging effects. Also the EtOAc-soluble portion revealed the highest phenolic contents as compared to the other extracts. Conclusions : These results indicate that phenolic compounds may be important constituents that give rise to the anti-AChE and antioxidative activities of A. yomena extract. Further phytochemical studies on this plant, for nutraceutical or pharmaceutical application, are warranted.

• 한국응용곤충학회지
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• 제30권1호
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• pp.18-28
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• 1991

집파리(Musca domestica L.)외 3종 곤충으로부터 0.01 M sodium phosphate buffer를 이용하여 AChE를 분리, 추출할 때 AChE의 안정성 및 buffer capacity를 고려한 적정 pH는 7.5였으며, 0.1M sidium phosphate buffer의 기질 수용액으로 AChE의 활성을 측정할 경우 효소의 활성화와 buffer capacity를 고려했을 때 pH는 7.5가 적합한 조건이었다. AChE 분리.추출을 위한 조직의 마쇄시에는 Potter Elvehjem homogenizer를 사용하였으며, 마쇄액을 원심분리하여 AChE현탁액을 조제할 때 집파리의 경우에는 성충 두부700g 상등액을, 벼멸구(Nilaparvata lugens Stal)는 5령 약충 전충체의 700g 상등액을, 배추좀나방 (Plutella xylostella L.)의 경우에는 5령 유충 전충체의 지질을 제거한 10,000g 상등액을, 그리고 담배거세미나방(Spodoptera litura F.)의 경우에는 4령 유충.두부의 700g 상등액을 AChE 0.2~0.5U 정도로 조정하여 효소원으로 사용하는 것이 대량조제, 추출수율 및 활성 측정상의 안정성등을 고려할 때 합리적인 것으로 조사되었다. 4종 곤충의 AChE현탁액을 $-18^{\circ}C$ 조건에서 냉동보관할 경우 3주까지는 90% 이상의 활성이 유지되었다. 집파리, 벼멸구 및 배추좀나방 AChE의 Km 값은 각각 0.042, 0.037 및 0.043 mM이었으며, 고농도에서 AChE 특이적 기질 저해 현상이 관찰되었으나 담배거세미나방 ChE의 경우에는 1.15 mM의 Km값을 가지며 BuChE적 특성을 보이는 듯 하나 추가실험이 요구된다. 각 곤충의 AChE를 대상으로 한 저해실험시의 적정 기질농도는 집파리, 벼멸구, 배추좀나방의 경우에는 공히 0.5 mM 그리고 담배거세미나방의 경우는 12 mM 이었다.

• Bulletin of the Korean Chemical Society
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• 제34권11호
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• pp.3322-3326
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• 2013

A series of hybrid molecules between (${\alpha}$)-lipoic acid (ALA) and benzyl piperazines were synthesized and their in vitro cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibitory activities were evaluated. Even though the parent compounds did not show any inhibitory activity against cholinesterase (ChE), all hybrid molecules showed BuChE inhibitory activity. Some hybrid compounds also displayed AChE inhibitory activity. Specifically, ALA-1-(3-methylbenzyl)piperazine (15) was shown to be an effective inhibitor of both BuChE ($IC_{50}=2.3{\pm}0.7{\mu}M$) and AChE ($IC_{50}=30.31{\pm}0.64{\mu}M$). An inhibition kinetic study using compound 15 indicated a mixed inhibition type. Its binding affinity ($K_i$) value to BuChE is $2.91{\pm}0.15{\mu}M$.

• Bulletin of the Korean Chemical Society
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• 제32권spc8호
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• pp.2997-3002
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• 2011

A series of hybrid molecules between (R)-lipoic acid (ALA) and the acetylated or methylated polyphenol compounds were synthesized and their in vitro cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibition activities were checked. The $IC_{50}$ values of all hybrid molecules for a BuChE inhibition were lower than those of the single parent compounds. Specifically, ALA-acetyl protected caffeic acid (11, ALA-AcCA) was shown as an effective inhibitor of BuChE ($IC_{50}=0.5{\pm}0.2\;{\mu}M$) and also had a great selectivity for BuChE over AChE (more than 800 fold). Inhibition kinetic study indicated that 11 is a mixed inhibition type. Its binding affinity ($K_i$) value to BuChE is $1.52{\pm}0.18\;{\mu}M$.

• 동의신경정신과학회지
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• 제28권2호
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• pp.123-136
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• 2017

Objectives: The objective of this study is to investigate the anti-amnesic effects of AR, Aucklandiae Radix, ground powder on scopolamine (Sco)-induced memory impairment in mice (C57BL/6) through its favorable acetylcholine (ACh) and acetylcholinesterase (AChE) activity, Choline acetyltransferase (ChAT) mRNA expression, and antioxidant effect. Methods: Six groups, a total of 20 intact or 100 Sco treated mice, were selected based on their body weights and were used in this study. Half of the mice in each group were used for the passive avoidance task test and the measurements of hippocampus ACh content, AChE activity and ChAT mRNA expression. The remaining half of the mice in each group were used for the Morris water maze test and cerebral antioxidant defense system measurement. Results: Marked decreases in step-through latency times in the passive avoidance task test and increases in escape latency times in the Morris water maze test were observed with decreases in the hippocampus ACh content and ChAT mRNA expression, and increases in the hippocampal AChE activities, as a result of Sco intraperitoneal treatment, in the present study. In addition, destruction of the cerebral cortex antioxidant defense systems was observed in Sco control mice as compared with intact vehicle control mice. However, 28 days of continuous oral pre-treatment with AR ground powder at doses of 400, 200 and 100 mg/kg markedly and dose-dependently inhibited the Sco treatment-related amnesia. Conclusions: The results prove that oral administration of AR ground powder reduces Sco-induced memory impairment. This is because it can preserve ACh, related to ChAT mRNA expression, cause AChE inhibition, and activate the cerebral antioxidant defense system.

• 동의신경정신과학회지
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• 제30권3호
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• pp.221-235
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• 2019

Objectives: The purpose of this study was to confirm the anti-amnesic effects of Bunsimgieum (BSGE) through its favorable acetylcholine (ACh) and, acetylcholinesterase (AChE) activity, choline acetyltransferase (ChAT) mRNA expressions, and antioxidant effect on scopolamine (Sco)-induced memory impairment in C57BL/6 mice. Methods: Six groups, a total of 20 intact or 100 Sco-induced mice were used in this study, based on their body weight. Half of each group underwent passive avoidance tests and the measurement of hippocampus AChE activity, ACh content, and ChAT mRNA expression, The remaining half of each group underwent a Morris water-maze test and antioxidant defense system measurement as well. Results: Significant reductions in the step-through latency times from the passive avoidance test and reductions in the escape latency times from the Morris water-maze test were observed with increases of hippocampal AChE activities and, reductions in ACh contents and ChAT mRNA expression in hippocampus, as a result of Sco intraperitoneal treatment, in this study. Additionally, the increases in cerebral cortical MDA levels and, reductions in GSH contents, SOD activities, and CAT activities were demonstrated in the Sco control mice compared with the intact vehicle control mice, respectively. However, 28 days of consecutive oral pre-treatment of BSGE hot water extracts of 400, 200, and 100 mg/kg, respectively, markedly and dose-dependently inhibited Sco treatment-related amnesia. Conclusions: The results demonstrate that the oral administration of BSGE hot water extracts reduces Sco-induced memory impairment, through preserving ACh, related to ChAT mRNA expressions, causes AChE inhibition, and enhances the cerebral antioxidant defense system.

• 한국자원식물학회지
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• 제31권5호
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• pp.433-452
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• 2018

본 연구는 천연식물자원을 대상으로 치매의 일종인 알츠하이머병을 개선 및 치료할 수 있는 소재를 발굴하기 위해 식물추출물에 대해 콜린성 에스테라제(AChE) 저해활성을 탐색하였다. 184개의 식물추출물을 $100{\mu}g/ml$의 단일농도에서 아세틸콜린에스테라제(AChE)을 실험한 결과, 10% 이상의 AChE 저해활성을 보였던 추출물은 황벽나무(Phellaodendron amurense Rupr., 수피, 메탄올 추출물), 황벽나무(Phellaodendron amurense Rupr., 수피, 물 추출물), 연꽃(Nelumbo nucifera Gaertn., 수술/자방, 메탄올 추출물), 쪽(Persicaria tinctoria H. GROSS, 꽃, 메탄올 추출물), 중국황련(Coptis chinensis, 뿌리줄기, 메탄올 추출물), 육계(Cinnamomum cassia Blume, 수피, 에탄올 추출물) 및 잇꽃(Carthamus tinctorius L., 열매, 에탄올 추출물) 등 7개가 확인되었다. 선발된 7개의 추출물에 대해서는 25, 20, 100 및 $200{\mu}g/ml$의 최종농도에서 AChE 및 BuChE에 대한 저해활성을 검정하였다. 그 결과, AChE 저해활성에서는 연꽃(Nelumbo nucifera Gaertn.) 수술/자방의 메탄올 추출물이 $15.0{\pm}3.4%{\sim}73.5{\pm}3.6%$, 쪽(Persicaria tinctoria H. GROSS) 꽃의 메탄올 추출물이 $19.5{\pm}9.1%{\sim}63.5{\pm}5.4%$, 중국황련(Coptis chinensis) 뿌리줄기의 메탄올 추출물이 $81.6{\pm}0.4%{\sim}58.5{\pm}2.4%$, 황벽나무(Phellaodendron amurense Rupr.) 수피의 메탄올 추출물이 $69.9{\pm}1.8%{\sim}80.5{\pm}0.9%$, 그리고 황벽나무 (Phellaodendron amurense Rupr.) 수피의 물 추출물이 $54.8{\pm}0.6%{\sim}78.3{\pm}2.6%$의 값을 보였다. BuChE 저해활성에서는 연꽃(Nelumbo nucifera Gaertn.) 수술/자방의 메탄올추출물, 쪽(Persicaria tinctoria H.GROSS) 꽃의 메탄올추출물 및 중국황련(Coptis chinensis) 뿌리줄기의 메탄올추출물이 각각 $58.9{\pm}7.8{\sim}81.6{\pm}1.9%$ 및 $45.8{\pm}9.8%{\sim}72.4{\pm}2.5%$ 및 $33.1{\pm}9.9%{\sim}55.4{\pm}5.4%$의 순으로 높은 BuChE 저해활성을 나타내었다. 이러한 실험결과를 종합하여 볼때, 연꽃(Nelumbo nucifera Gaertn.)의 수술/자방, 쪽(Persicaria tinctoria H. GROSS)의 꽃, 중국황련(Coptis chinensis)의 뿌리줄기, 황벽나무(Phellaodendron amurense Rupr.)의 수피는 알츠하이머병(AD)의 개선 효과를 나타낼 수 있는 후보 소재로 사료되었다.