• 대한본초학회지
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• 제37권4호
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• pp.39-48
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• 2022

Objectives : In the present study, we assessed the effects of water extract of Ulmus davidiana(UED) on the learning and memory impairments induced by scopolamine in mice through its favorable acetylcholinesterase (AChE) activity and antioxidant effect. Methods : The memory and cognitive enhancing effect of the UDE was investigated using a passive avoidance test, the Morris water maze test and Y-maze test in mice. In addition, to examine the mechanism of UDE using acetylcholinesterase (AChE) and antioxidant activity. Results : The water extract of UDE (100, and 200 mg/kg) significantly reversed the scopolamine-induced cognitive impairments in the passive avoidance test (P < 0.05). Moreover, UDE (100, and 200 mg/kg) 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). On the Y-maze test, UDE (100, and 200 mg/kg) also significantly reversed scopolamine-induced cognitive impairments in mice (P < 0.05). In an in vitro study, UDE was found to inhibit acetylcholinesterase, changes in neurotrophic factor (CREB), and antioxidant activity in a dose-dependent manner. Conclusions : The water extract of UDE dramatically possesses the anti-amnestic and cognitive-enhancing activities related to the memory processes, and these activities were parallel to treatment duration and dependent on the learning models. These results suggest that the administration of UDE enhances learning and memory, and that this effect is partially mediated by ERK-CREB-BDNF signaling and the survival of immature neurons.

• 한국식품저장유통학회지
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• 제20권6호
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• pp.840-845
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• 2013

본 연구에서는 20종 생약 열수추출물의 AChE 활성, 산화스트레스로 인한 지질 과산화물 생성 억제능 및 뇌신경세포 사멸에 대한 보호효과를 비교하였다. AChE의 억제활성은 산수유, 감초, 당귀 열수추출물에서 우수하였으며, 그 중 산수유가 가장 높은 억제율을 나타내었다. 또한 $H_2O_2/FeSO_4$로 산화 스트레스를 유발시켜 생약 열수추출물의 지질과산화물 생성 억제 활성을 조사한 결과 소엽, 하수오, 계피 및 감초 열수추출물에서 높은 항산화 활성을 보였다. L-Glutamate에 의해 유도된 신경세포 독성에 대한 보호효과는 감초, 계피, 길경, 박하 열수추출물의 $100{\mu}g/mL$ 농도에서 관찰되었다. 본 연구를 종합적으로 살펴보았을 때, 감초 열수추출물이 치매 예방 및 개선제로써의 활용가능성이 가장 뛰어난 것으로 판단된다. 향후 치매예방 효능을 가지는 새로운 화합물 발굴을 위한 기초자료로 활용될 것으로 사료된다.

• Natural Product Sciences
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• 제29권2호
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• pp.74-82
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• 2023

Nepeta sibirica L. or Siberian catmint is a medicinal plant species used in Mongolian traditional medicine for curing human different disorders and veterinary practices. The previous study of the whole plant concentrated on the determination of its essential oil composition and reported that the major ones are sesquiterpenes, including nepetalactone. The aim of this study was to reveal a new biological activity of the above-ground parts of N. sibirica L. and compare the activity of different extracts correlating with the content of biologically active compounds and evaluate their toxicity. For this purpose, anti-oxidative and acetylcholinesterase inhibitory activities of the above-ground parts of N. sibirica L. aqueous and ethanol (EtOH) (40%, 70%) extracts were assayed spectrophotometrically. The aqueous extract showed positive anti-oxidative activity by both tested DPPH and FRAP assays with IC₅₀ 134.24 ± 1.42 mg/mL and FRAP value 1385.15 ± 8.12 µmol/L at 200 ㎍/mL, in contrast to 40% and 70% EtOH extracts. The 70% EtOH extract presented the highest acetylcholinesterase inhibitory activity (IC₅₀ 77.29 ± 0.38 mg/mL) followed by 40% EtOH extract (176.72 ± 0.35 mg/mL) and aqueous extract (275.41 ± 0.23 mg/mL). Total phenolics were found to be gallic acid equivalent, % 3.74 ± 0.05 (70% EtOH), 3.94 ± 0.04 (40% EtOH), and 3.79 ± 0.16 (aqueous), whereas the total flavonoids as a rutin equivalent, % as 2.01 ± 0.12, 1.44 ± 0.17 and 1.99 ± 0.02, each. The aqueous extract showed the best anti-oxidative and lowest activity against the acetylcholinesterase; however, the 70% EtOH extract showed the opposite effects than that of the aqueous. No mortality incidence was visible at various doses, indicating that the oral median lethal dose of aqueous and 70% EtOH extracts were considered greater than 5000 mg/kg. N. sibirica L. belongs to the non-toxic category of the OECD 423 classification.

• 생명과학회지
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• 제23권12호
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• pp.1525-1531
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• 2013

백일주는 찹쌀, 백미, 누룩, 재래종 국화꽃, 오미자, 진달래, 솔잎 및 물을 넣고 100일간 발효 숙성시킨 전통주이다. 본 연구에서 백일주의 생리활성을 알아보기 위하여 총 폴리페놀과 플라보노이드 함량, 항산화 활성(DPPH 라디칼, ABTS 라디칼, 아질산염 소거활성), 혈전용해활성, angiotensisn 전환효소 저해활성 및 acetylcholinesterase 저해활성을 평가하였다. 살균 처리되지 않은 백일주와 살균 처리된 백일주의 총 폴리페놀 함량은 391.59와 401.33 ${\mu}g$ tannic acid equivalents/ml이었고, 총 플라보노이드 함량은 284.75와 308.35 ${\mu}g$ quercetin equivalents/ml이었다. 백일주의 항산화 활성(DPPH 라디칼, ABTS 라디칼, 아질산염 소거활성)은 청주 보다 우수한 것으로 나타났다. 또한 백일주의 혈전용해활성과 acetylcholinesterase 저해활성도 청주에 비해 우수한 것으로 나타났다. 반면에 angiotensin 전환효소 저해활성을 측정한 결과 살균 처리되지 않은 백일주는 23.62%, 살균 처리된 백일주는 19.99%, 청주는 38.91%로 청주가 가장 높은 것으로 나타났다. 따라서 본 연구 결과는 백일주가 항산화 효과와 혈전용해 활성이 있음을 시사하고 있다.

• Biomolecules & Therapeutics
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• 제26권3호
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• pp.274-281
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• 2018

A previous study in humans demonstrated the sustained inhibitory effects of donepezil on acetylcholinesterase (AChE) activity; however, the effective concentration of donepezil in humans and animals is unclear. This study aimed to characterize the effective concentration of donepezil on AChE inhibition and impaired learning and memory in rodents. A pharmacokinetic study of donepezil showed a mean peak plasma concentration of donepezil after oral treatment (3 and 10 mg/kg) of approximately $1.2{\pm}0.4h$ and $1.4{\pm}0.5h$, respectively; absolute bioavailability was calculated as 3.6%. Further, AChE activity was inhibited by increasing plasma concentrations of donepezil, and a maximum inhibition of $31.5{\pm}5.7%$ was observed after donepezil treatment in hairless rats. Plasma AChE activity was negatively correlated with plasma donepezil concentration. The pharmacological effects of donepezil are dependent upon its concentration and AChE activity; therefore, we assessed the effects of donepezil on learning and memory using a Y-maze in mice. Donepezil treatment (3 mg/kg) significantly prevented the progression of scopolamine-induced memory impairment in mice. As the concentration of donepezil in the brain increased, the recovery of spontaneous alternations also improved; maximal improvement was observed at $46.5{\pm}3.5ng/g$ in the brain. In conclusion, our findings suggest that the AChE inhibitory activity and pharmacological effects of donepezil can be predicted by the concentration of donepezil. Further, $46.5{\pm}3.5ng/g$ donepezil is an efficacious target concentration in the brain for treating learning and memory impairment in rodents.

• 한국환경농학회지
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• 제6권2호
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• pp.77-83
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• 1987

유기인계(有機燐系) 살충제인 phorate 가 병아리의 Acetylcholin esterase 활성(活性) 저해(沮害)에 미치는 영향(影響)을 조사한 결과(結果)는 다음과 같았다. Phorate와 그 대사물(代謝物)에 대(對)한 AChE 및 ChE 활성(活性)의 $I_{50}$값은 phosphorothiolate형(型)(표현불가)이 phosphorodithiolate형(型)(표현불가)보다 약(約) $700{\sim}2500$배(培) 낮았으며, 측쇄(側鎖)의 산화(酸化) 상태별(狀態別)로 보면 sulfide>sulfoxide>sulfone의 순(順)으로 $I_{50}$값이 낮은 경향(傾向)이었다. 병아리에 대(對)한 phorate의 급성경구독성(急性經口毒性)은 1.02mg/kg 이었다. Phorate를 급성경구독성(急性經口毒性) $LD_{50}$값 이하(以下)로 경구(經口) 투여(投與)하였을 때 투여(投與) 후(後) 초기(初期)에는 혈장(血漿) ChE 활성(活性)이 뇌(腦) AChE 활성(活性)보다 더 크게 저해(沮害)되었으나, 효소활성(酵素活性)의 회부(回復)은 뇌(腦) AChE 보다 혈장(血漿) ChE 가 더 빠른 경향(傾向)을 보였다.

• 한국토양비료학회지
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• 제40권4호
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• pp.274-279
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• 2007

4 종류의 폐기물(생활하수오니, 공단하수오니, 피혁오니, 주정오니)과 대조구로서 돈분퇴비가 지렁이에게 미치는 독성을 평가하기 위하여 대표적인 유해성 평가 biomarker 3종류 (acetylcholinesterase, cytochrome $P_{450}$, heat shock protein 70)를 사용하였다. 유기성 폐기물에 대한 acetylcholinesterase의 활성은 돈분퇴비의 경우 활성이 약간 촉진된 반면 생활하수오니, 공단하수오니, 피혁오니, 주정오니는 영향을 미치지 않았다. Cytochrome $P_{450}$의 활성은 공단하수오니와 피혁오니는 활성을 억제하였고 생활하수오니, 주정오니, 돈분퇴비는 영향을 미치지 않았다. 또한 Hsp70의 발현량은 증류수보다 돈분퇴비는 1.9배, 주정오니는 3.0배, 생활하수오니는 3.3배, 공단오니는 4.4배, 피혁오니는 4.7배 순으로 지렁이 (Eisenia fetida)에게 스트레스를 많이 주었다. 이상의 결과로부터, 4 종류의 폐기물(생활하수오니, 공단하수오니, 피혁오니, 주정오니)은 돈분퇴비보다 독성이 강한 것으로 판단하였다. 또한 AChE, Cytochrome $P_{450}$과 Hsp70은 추후 유기성 폐기물의 유해성을 모니터링하기에 적합한 biomarker로서 가치가 있다고 생각한다.

• Applied Biological Chemistry
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• 제41권4호
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• pp.213-217
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• 1998

An assay for cytochrome P450 monooxygenase activity by determination of the products of organophosphate oxidation via inhibition of acetylcholinesterase was described. Extracts from strains of Oryzaephilus surinamensis selected for resistance to chlorpyrifos-methyl (QVOS 102), fenitrothion (VOS F) and malathion (VOS 3), and a standard susceptible strain VOS 48, were incubated with an organophosphate in the presence of a NADPH-generating system and acetylcholinesterase. The degree of inhibition of the acetylchoinesterase activity was converted to manooxygenase activity using standard curves for the inhibition of acetylcholiesterase by chlorpyrifos-methyl-oxon, fenitrooxon and malaoxan. Activity was detectable in VOS 48 and was present at different increased levels with the different organophosphates in the three resistant strains, suggesting that different forms of P450 might be involved in organophosphate oxidation in these insects. The assays were carried out using crude insect homogenates and much smaller samples of insect material than the standard aldrin to dieldrin assay. It should be possible to use the method for determination of monooxygenase activity in single insert.

• Archives of Pharmacal Research
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• 제25권6호
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• pp.856-859
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• 2002

In the course of finding Korean natural products for acetylcholinesterase (AChE) inhibitory activity, we found that a methanolic extract of the roots of Angelica dahurica showed significant inhibitory effects on AChE. Bioassay-guided fractionation of the methanolic extract resulted in the isolation of three furanocoumarins, isoimperatorin (1), imperatorin (2) and oxypeucedanin (3), as active principles. These compounds inhibited AChE activity in a dosedependent manner, and the $IC_{50}$ values of compounds 1-3 were 74.6, 63.7 and 89.1 uM, respectively.

• 약학회지
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• 제35권5호
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• pp.438-443
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• 1991

This study was designed to examine the effects of diphenhydramine and papaverine on the toxic manifestations of cholinesterase inhibitors. It was found that papaverine increase acetylcholinesterase activity in cerebral cortex of mice. Papaverine pretreatment tended to increase acetylcholinesterase activity against the actions of neostigmine and physostigmine. When diphenhydramine (20~30 mg/kg, s.c.) was treated 20 min before the administration of cholinesterase inhibitor, it significantly extended the onset latency in the signs of toxicosis which were characteristically produced by physostigmine (0.25~1.5 mg/kg, s.c.) or neostigmine (0.125~0.5 mg/kg, s.c.), and it also prevented lethality in all of the animals.