• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.2
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• pp.374-380
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• 2009

Samryungbaikchul-san(SRBCS) has been used in oriental medicine for the treatments of gastrointestinal and neurological disorders. Here, potential protective function of SRBCS was investigated in neural tissues in Alzheimer's disease(AD) mouse model. In primary cultured cells from the spinal cord of newborn rats, treatment of ${\beta}$-amyloid peptide elevated cell counts positive to glial fibrillary acidic protein(GFAP) or caspase 3 immunoreactivity, but the co-treatment of SRBCS reduced positive cell counts. In vivo administration of scopolamine, an inhibitor of muscarinic receptor, resulted in increases in the number of glial fibrillary acidic protein(GFAP) and caspase 3-positive cells in hippocampal subfields, which was then decreased by the treatment of SRBCS or acetylcholinesterase inhibitor galathamine. The present data suggest that SRBCS may play a protective role in damaged neural tissues caused by scopolamine treatments in mice.

• Bulletin of the Korean Chemical Society
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• v.28 no.2
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• pp.225-228
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• 2007

Lipoic acid (LA) is a multifunctional antioxidant against a variety of ROS. Nitrone acts as free radical spin trap and exhibits neuroprotective activity. Thus, LA-nitrone derivatives (6, 7, 8, and 9) were synthesized and screened as an antioxidant and inhibitors for cholinesterases. Even though the antioxidant effect of LA-nitrone derivatives was not improved, they turned out to be effective inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in μM range.

• Bulletin of the Korean Chemical Society
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• v.32 no.8
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• pp.2593-2598
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• 2011

Polyphenols (PPs) are known as antioxidant compounds having benign biological activities. In this paper, a series of hybrid molecules between the free or acetyl protected polyphenol compounds were synthesized and their in vitro antioxidant activity (DPPH assay) and cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibition activities were evaluated. As expected, free phenolic hybrid compounds (6 and 8) showed better antioxidant activity than acetyl protected hybrid compounds (5 and 7) from DPPH assay. But the contrast result was obtained from BuChE inhibition assay. Acetyl protected hybrid compounds (5 and 7) showed better inhibition activity for BuChE than free phenolic hybrid compounds (6 and 8). Specifically, 10 (AcFA-AcFA) were shown as an effective inhibitor of BuChE ($IC_{50}=2.3{\pm}0.3{\mu}M$) and also had a great selectivity for BuChE over AChE (more than 170 fold). Inhibition kinetic studies with acetyl protected compounds (5, 7, 9, and 10) indicated that 5, 7 and 10 are a hyperbolic mixed-type inhibition and 10 is a competitive inhibition type. The binding affinity (Ki) value of 10 to BuChE is $2.32{\pm}0.15{\mu}M$.

• The Korean Journal of Food And Nutrition
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• v.23 no.2
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• pp.226-232
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• 2010

새로운 항치매성 건강식품을 개발하기 위해 아세틸콜린에스터레이즈(AChE)를 강력하게 저해하는 추출물을 곡류와 두류의 다양한 추출물로부터 선발한 후 최적 추출 조건을 조사하였다. 추출물 중 수수 메탄올 추출물이 63.4%의 가장 높은 AChE 저해 활성을 보였다. 수수를 80% 메탄올로 $40^{\circ}C$에서 12시간 추출했을 때 최대의 AChE 저해 활성을 나타내었다. AChE를 저해하는 수수 메탄올 추출물의 영양성과 생리 기능성을 조사하였다. 메탄올 추출물은 유리당으로 고형물 100 g당 4.78 g의 포도당과 4.13 g의 자당 및 0.97 g의 과당을 함유하였다. 또한, 수수 메탄올 추출물의 고형물 100 g에 linoleic acid 273.82 mg, oleic acid 215.65 mg, palmitic acid 122.03 mg, stearic acid 4.96 mg을 함유하고 있었고, 주요 유기산으로 주석산 27.45 mg, 말론산 15.43 mg, 사과산 9.94 mg이 메탄올 추출물 1 g에 함유되어 있었다. 수수 메탄올 추출물은 항치매 활성 외에도 콜레스테롤 합성을 저해하는 HMG-CoA reductase 저해 활성이 50.2%이었고, 항산화 활성은 56.1%를 보였다.

• Journal of the Korean Chemical Society
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• v.60 no.2
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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.

• Biomolecules & Therapeutics
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• v.26 no.3
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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.

• Korean Journal of Plant Resources
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• v.30 no.1
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• pp.17-21
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• 2017

Since the acetylcholinesterase (AChE) inhibitor is used to treat Alzheimer's disease, the present study aimed to analyze the component with anti-AChE activity from the essential oil of Artemisia iwayomogi (Compositae). The four major components of the essential oil were identified to be camphor (29.8%), borneol (28.0%), eucalyptol (5.81%) and coumarin (5.49%) from a gas chromatography-mass spectrometry (GC-MS). The essential oil and its three components, camphor, borneol, and coumarin, were subjected to anti-AChE assay. The $IC_{50}$ values of the essential oil and coumarin were shown to be $0.298mg/m{\ell}$ and $0.236mg/m{\ell}$, though those of other two components, camphor and borneol, were more than $0.250mg/m{\ell}$. These results suggest that coumarin is an active substance of this essential oil with anti-AChE activity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.5
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• pp.791-796
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• 2004

This study was peformed to screen the biological activities of Pleurotus ferulea (K5 and K8 strains). The cap of K5 strain is well developed than stalk, and vice versa in K8. The ethanol extract of Pleurotus ferulea exhibited significant free radical scavenging activity (35∼36%), suggesting possible effect on many degenerative diseases originated from the reaction of oxygen species. Acetylcholinesterase inhibitor is proven to be the most effective factor for Alzheimer disease induction, and ethanol extract of Pleurotus ferulea significantly inhibited acetylcholinesterase activity (25∼35%) in uitro. Moreover, ethanol extract of Pleurotus ferulea suppressed liver fibrosis by 3∼12% in uitro. However, Pleurotus ferulea feruled to inhibit glucose uptake in human intestinal cell line. Viability of gastric and colon cancer cells was also not affected by Pleurotus ferulea extract. In conclusion Pleurotus ferulea exhibited significant effect on free radical scavenging, acetylcholinesterase inhibiton and brain cell protection. However, Pleurotus ferulea failed to affect glucose uptake, and cytotoxicity of gastric and cancer cells. In general, K8 revealed more significant effects than K5.

• Korean Journal of Clinical Laboratory Science
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• v.50 no.3
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• pp.225-235
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• 2018

Phellinus gilvus is a medicinal mushroom used that has been used in folk medicine in Asian countries for centuries. The aim of this study was to investigate the anti-xanthine oxidase, anti-cholinesterase, and anti-inflammatory activities of methanol (ME) and hot water (HW) extracts prepared from fruiting bodies of Ph. gilvus. ME and HW had good anti-xanthine oxidase (XO) activities compared to allopurinol, an inhibitor of xanthine oxidase. ME showed comparable and slightly lower inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), respectively, than galanthamine, a standard AChE and BChE inhibitor. ME also showed a protective effect against glutamate-induced cytotoxicity at 40 mg/mL and 100 mg/mL in PC-12 cells. ME (0.5~2.0 mg/mL) significantly inhibited nitric oxide (NO) production in RAW 264.7 murine macrophage cells stimulated with lipopolysaccharide (LPS). Carrageenan-induced hind-paw edema in rats was significantly reduced 2~6 hr after treatment with 50 mg/kg of ME, which was comparable to administration of 5 mg/kg of indomethacin, the positive control. These results demonstrate that ME and HW of Ph. gilvus fruiting bodies possess good anti-xanthine oxidase, anti-cholinesterase, and anti-inflammatory activities.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.165-170
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• 2023

Isolation of the culture broth of a marine-derived Acremonium sp. CNQ-049 guided by HPLC-UV yielded compound 1 (3-phenethyl-2-phenylquinazolin-4(3H)-one), and its inhibitory activities against monoamine oxidases (MAOs), cholinesterases (ChEs), and β-secretase 1 (BACE1) were evaluated. Compound 1 was an effective selective MAO-B inhibitor with an IC₅₀ value of 9.39 µM and a selectivity index (SI) value of 4.26 versus MAO-A. In addition, compound 1 showed a potent selective butyrylcholinesterase (BChE) inhibition with an IC₅₀ value of 7.99 µM and an SI value of 5.01 versus acetylcholinesterase (AChE). However, compound 1 showed weak inhibitions against MAO-A, AChE, and BACE1. The Ki value of compound 1 for MAO-B was 5.22±1.73 µM with competitive inhibition, and the Ki value of compound 1 for BChE was 3.00±1.81 µM with mixed-type inhibition. Inhibitions of MAO-B and BChE by compound 1 were recovered by dialysis experiments. These results suggest that compound 1 is a dual-functional reversible inhibitor of MAO-B and BChE, that can be used as a treatment agent for neurological disorders.