• Journal of Microbiology
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• 제44권5호
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• pp.502-507
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• 2006

In a previous study, an extract of Clavicorona pyxidata DGUM 29005 mycelia demonstrated an inhibitory effect against enzyme-associated perceptual disorders. We have attempted to determine whether this mycelial extract is also capable of inhibiting the activities of acetylcholinesterase (AChE) and ${\beta}$-secretase (BACE) activity. Butanol, ethanol, and water extracts of C. pyxidata DGUM 29005 mycelia were shown to inhibit AChE activity by 99.3%, 93.7%, and 91.7%, respectively. The inhibitory value of the butanol extract was more profound than that of tacrine (95.4%). The ethanol extract also exerted an inhibitory effect against BACE activity; this fraction may harbor the potential for development into a pharmocotherapeutic modality for the treatment of Alzheimer's disease (AD) patients. Rat pheochromocytoma PC12 cells in culture were not determined to be susceptible to the cytotoxic activity evidenced by the mycelial extract. The ethanol extract inhibited endogenous AChE activity in PC12 cellular homogenates, with an $IC_{50}\;of\;67.5{\mu}g/ml$, after incubation with intact cells, and also inhibited BACE activity in a dose-dependent fashion. These results suggest that the C. pyxidata mycelial extract has the potential to enhance cholinergic function and, therefore, may perform a function in the amelioration of the cholinergic deficit observed in cases of AD, as well as other types of age-associated memory impairment.

• 약학회지
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• 제55권6호
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• pp.473-477
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• 2011

Alzheimer's disease (AD), one of the most common forms of dementia, is a progressive neurodegenerative disorder symptomatically characterized by the decline in memory and cognitive abilities. To date, the successful therapeutic strategy to treat AD is to maintain the levels of acetylcholine (ACh) by inhibiting acetylcholinesterase (AChE) to lead five drugs in clinical use. In this study, several coumarin derivatives were designed based on the lead structure of scopoletin and evaluated for their AChE inhibitory activities.

• 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.

• Natural Product Sciences
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• 제28권3호
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• pp.138-142
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• 2022

Alzheimer's disease (AD) is the most common age-related neurodegenerative disease in industrialized countries. It is estimated that about 47 million people living with dementia and the number of cases will be tripled by 2050. However, the exact mechanism of AD is not known, and full therapy has still not been found. Various tryptophan-derived alkaloids have been reported as promising agents for the treatment of AD. In the present study, a series of tryptophan-derived alkaloids were isolated and characterized from the methanol extract of Hedera rhombea fruit. Based on the analysis of their observed and reported spectroscopic data, their structures were identified as N-[4'-hydroxy-(E)-cinnamoyl]-L-tryptophan (1), N-[3',4'-dihydroxy-(E)-cinnamoyl]-L-tryptophan (2), N-[4'-hydroxy-(E)-cinnamoyl]-L-tryptophan methyl ester (3), and N-[3',4'-dihydroxy-(E)-cinnamoyl]-L-tryptophan methyl ester (4). These compounds were screened for anti-Alzheimer activity via their inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes in vitro. As a result, compounds 3 and 4 showed moderate BChE inhibition with IC₅₀ values of 86.9 and 78.4 μM, respectively, compared to those of the positive control [berberine (IC₅₀ = 11.5 μM)]. However, all four compounds did not show significant inhibition of the AChE enzyme. This is the first time, the AChE and BChE inhibitory activities of these tryptophan-derived alkaloids were investigated and reported.

• 대한화학회지
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• 제60권2호
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• pp.125-130
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• 2016

With the goal of developing Alzheimer’s disease therapeutics, we have designed and synthesized new triazole linked decursinol derivatives having potency inhibitory activities against cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)]. Since inhibition of cholinesterase (ChE) is still considered to be one of the most effective targets to treat AD patients, many new classes of ChE inhibitors have been synthesized. In an effort of identifying new type of cholinergic drug, decursinol derivatives 11-17 have been synthesized between decursinol and other biological interesting compounds such as lipoic acid, polyphenols, etc by using the click reaction and then evaluated their biological activities. Compound 12 (IC₅₀ = 5.89 ± 0.31 mM against BuChE) showed more effective inhibitory activity against BuChE than galantamine (IC₅₀ = 9.4 ± 2.5 mM). Decursinol derivatives can be considered a new class inhibitor for BuChE and can be applied to be a novel drug candidate to treat AD patients.

• 생약학회지
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• 제33권3호통권130호
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• pp.211-218
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• 2002

The methanol extracts of 340 kinds of Korean medicinal herbs were examined in vitro for the inhibitory effect on the acetylcholinesterase (AChE, E.C. 3.1.1.7) from electric eel using acetylthiocholine as a substrate. Among tested, the extracts of Coptidis Rhizoma, Phellodendri Cortex, Evodiae Fructus, Myrrha, Arecae Semen and Piperis nigri Fructus were found to exhibit a significant inhibition upon the acetylcholinesterase in a dose dependent manner, respectively.

• 농업생명과학연구
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• 제45권4호
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• pp.113-120
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• 2011

본 연구에서는 생마늘 추출 숙성물의 용매 분획물에 대한 항산화 효과와 acetylcholinesterase (AChE) 저해 효과에 대해서 조사하였다. 생마늘 추출 숙성물의 헥산, 클로포름, 에틸아세테이트 및 물 분획물을 통한 총 페놀성 화합물의 함량은 각각 3.70, 23.63, 31.27, 2.35 mg/g으로 나타났다. 또한, 에틸아세테이트 분획물이 ABTS radical scavenging activity, ferric reducing antioxidant power 및 linoleic acid를 활용한 지질의 자동산화 저해 효과에서 가장 높다는 것을 확인하였다. 추가적으로, PC12 신경 세포에서의 에틸아세테이트 분획물의 처리가 $H_2O_2$가 유발시키는 산화적 스트레스의 수준을 감소시켰다. 결국 생마늘 추출 숙성물의 에틸아세테이트 분획물이 농도 의존적으로 AChE를 저해한다는 것을 확인하였다. 그러므로 본 연구는 생마늘 추출 숙성물의 에틸아세테이트 분획물이 PC12 신경세포에 있어서 산화적 스트레스 수준을 감소시키고, 또한 AChE 저해제로서 활용될 수 있는 가능성을 확인하였다.

• 한국식품영양과학회지
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• 제34권3호
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• pp.427-432
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• 2005

본 연구에서는 퇴행성 질환의 하나인 치매의 예방 및 치료를 위한 물질 탐색의 기초자료로서 식물 추출물에서 AChE 저해와 항산화 활성을 살펴보았다. AChE 효소의 저해 활성을 살펴본 결과, 식물 전초(whole plant) 추출물에서는 당근, 땃딸기와 고추나물에서 20%-30% AChE 저해 활성을 보였으며, 또한 식물 부위별(stem, leaf, fruit, root) 추출물의 AChE저 해 활성을 살펴본 결과, 줄기 부위 추출물에서는 은행나무(Gingko biloba)가 32.1%, 잎 부위 추출물에서는 산철쭉(Rhododendron yedoensa var. poukhanense)이 33.9%, 열매 부위 추출물에서는 선인장(Opuntia ficus-indica var. saboen)이 18.2%의 AChE 저해 활성을 보였다. 항산화 활성을 살펴본 결과, 식물 전초에서는 땃딸기(Fragaria yezoensis)에서 90.4%의 라디칼 제거 효과로 L-ascorbic acid와 거의 유사한 항산화력이 나타나났다. 식물 부위별 추출물의 라디칼 제거 효과를 살펴본 결과, 줄기와 뿌리 부위 추출물의 은행나무, 잎 추출물에서 털진달래(Rhododendron mucronulatum var. ciliatum)가 약 90%의 라디칼 제거 효과를 보였으며, 열매 부위 추출물의 산수유(Cornus officinalis)는 약 95% DPPH 라디칼 제거 효과로 가장 높은 항산화 활성을 보였다. 따라서 식물 전초 추출물의 땃딸기와 고추나물, 식물 부위별 추출물에서는 줄기 부위의 은행나무와 잎 부위의 산철쭉이 AChE 효소 저해와 항산화력 활성이 높으므로 퇴행성 질환의 하나인 치매를 예방하고 치료하는데 도움이 될 것으로 기대된다.

• Fisheries and Aquatic Sciences
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• 제25권2호
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• pp.49-63
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• 2022

Anti-cholinesterase (ChE)s are commonly prescribed as the symptomatic treatment of Alzheimer's disease. They are applied to prevent the breakdown of neurotransmitter acetylcholine (ACh) that bind to muscarinic and nicotinic receptors in the synaptic cleft. Seaweeds are one of the richest sources of bioactive compounds for both nutraceuticals and pharmacognosy applications. This study aimed to determine the anti-ChEs activity of Gracilaria manilaensis, one of the red seaweeds notables for its economic importance as food and raw materials for agar production. Methanol extracts (GMM) of G. manilaensis were prepared through maceration, and further purified with column chromatography into a semi-pure fraction. Ellman assay was carried out to determine the anti-acetylcholinesterase (AChE) and anti-butyrylcholinesterase (BuChE) activities of extracts and fractions. Lineweaver-Burk plot analysis was carried out to determine the inhibition kinetic of potent extract and fraction. Major compound(s) from the most potent fraction was determined by liquid chromatography-mass spectrometry (LCMS). GMM and fraction G (GMMG) showed significant inhibitory activity AChE with EC₅₀ of 2.6 mg/mL and 2.3 mg/mL respectively. GMM and GMMG exhibit mixed-inhibition and uncompetitive inhibition respectively against AChE. GMMG possesses neuroprotective compounds such as cynerine A, graveolinine, militarinone A, eplerenone and curumenol. These findings showed a promising insight of G. manilaensis to be served as a nutraceutical for neuronal health care in the future.

• Ocean and Polar Research
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• 제39권1호
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• pp.45-49
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• 2017

During the search for anticholinesterase compounds from marine organisms, we were able to isolate 6,6'-bieckol from a red alga, Grateloupia elliptica. This compound showed moderate acetylcholinesterase (AChE) inhibitory activity in a micromole range ($IC_{50}$ $44.5{\mu}M$). However, for butyrylcholinesterase (BuChE), a new target for the treatment of Alzheimer's disease (AD), it showed particularly potent inhibitory activity ($IC_{50}$ $27.4{\mu}M$), which is more potent compared to AChE. It also inhibits BACE-1, a new target for reducing the generation of ${\beta}-amyloid$.