• Korean Journal of Food Science and Technology
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• v.41 no.4
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• pp.435-440
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• 2009

Acetylcholinesterase (AChE) inhibitors, which enhance cholinergic transmission by reducing the enzymatic degradation of acetylcholine, are the only source of the compound that is currently approved for the treatment of Alzheimer's disease (AD). In these experiments, the concentration samples of green tea extracts were 100, 500, and 1,000 ${\mu}g$/mL. Among them, the highest concentration (1,000 ${\mu}g$/mL) of fresh green tea extracts showed the most potent inhibitory effect on AChE by reducing more than 40% of enzyme activity, and in a concentration-dependent pattern. In addition, we examined the effect of other storing conditions on AChE inhibition. In order to maintain storage for 3 months, the materials were held at the certain storing conditions of temperature (room temperature, 4 and $-20^{\circ}C$) and for water activity (0.81, 0.69, and 0.23). In these storing conditions, the difference in temperature did not contribute to the AChE inhibitory effect. Our presented data showed that the AChE inhibitory effect was affected by the concentration of green tea extract and by water activity (0.81). These results suggest that green tea may serve as a potential dietary source of AChE inhibitor.

• Applied Biological Chemistry
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• v.31 no.1
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• pp.92-99
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• 1988

The responses of brain acetylcholinesterase and plasma cholinesterase activities were examined in chicken given oral doses of an organophosphorus insecticides. Acute oral $LD_{50}$ of terbufos was 1.82mg/kg, and terbufos sulfone was 2.85mg/kg, terbufos sulfoxide, terbufoso xon, terbufosoxon sulfone and terbufosoxon sulfoxide were about $0.30{\sim}0.79mg/kg$, respectively. Acute oral $LD_{50}$ of phorate was 1.02mg/kg, and phorate sulfone was 1.73mg/kg, phorate sulfoxide, phoratoxon, phoratoxon sulfoxide and phoratoxon sulfone were about $0.36{\sim}0.63mg/kg$, respectively. Dosages of 50% inhibition for brain AChE and plasma ChE activities in chicken at 60 mins after oral administration of organop hosphorus insecticides were $35.3{\pm}6.8%\;and\;17.4{\pm}3.6%$ of acute oral $LD_{50}$, respectively. Activities of brain AChE and plasma ChE in chicken at 60 mins after oral administratration of acute oral $LD_{50}$ of organophosphorus insecticides were inhibited by $83.7{\pm}3.9%\;and\;93.3{\pm}2.2%$, respectively.

• Journal of Ginseng Research
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• v.34 no.4
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• pp.348-354
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• 2010

Black ginseng and white ginseng were extracted with 80% ethanol and evaluated for relative ginsenoside composition, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, and antioxidant properties. As analyzed by HPLC, black ginseng contained a greater proportion of ginsenoside $Rg_3$ compared to white ginseng. White ginseng was characterized by undetectable ginsenoside $Rg_3$ but it contained more total ginsenosides than black ginseng. Black ginseng extract exhibited higher (p<0.05) free radical-scavenging activity, as well as higher antioxidant activities than white ginseng against 2,2-diphenyl-1-picryl-hydrazyl, superoxide dismutase, and xanthine oxidase, despite the fact that the total saponin content was higher in white ginseng than black ginseng. In addition, the black ginseng extract displayed greater AChE and BChE inhibitory activities. These results suggest that black ginseng has stronger effects on anti-oxidation and AChE and BChE inhibition than white ginseng.

• Natural Product Sciences
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• v.17 no.2
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• pp.108-112
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• 2011

Several isoquinoline alkaloids (1 - 18), which have basic chemical structures as protoberberine and aporphine skeletones, were evaluated for their inhibitory activities on AChE and BuChE. Among them, compounds 3, 4, 6, 8 and 12 showed the potent AchE activity with the $IC_{50}$ values ranging from $10.2{\pm}0.5\;{\mu}M$ to $24.5{\pm}1.6\;{\mu}M$, meanwhile, compound 14 - 17 exhibited strong inhibitory activity with $IC_{50}$ values from $2.1{\pm}0.2$ to $5.5{\pm}0.3\;{\mu}M$. Compounds 14 - 17 exhibited selective inhibition for AChE compared with BuChE. The isoquinoline alkaloid possesses aromatic methylenedioxy groups and quaternary nitrogen atoms are crucial for the anti-cholinesterase inhibitory activity.

• The Journal of Korean Medicine
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• v.25 no.4
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• pp.1-7
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• 2004

Objective : This study was designed to examine the effects of orally administered Prunus persica water extract (PPE), which is used as herbal medicine, for treatment of Yu Xue (stasis of blood) and tacrine on the basal concentration of extracellular acetylcholine in the hippocampus of rats. Methods: To investigate the effects of PPE and tacrine on concentration of extracellular acetylcholine in the hippocampus of rats, the microdialysis technique, under the same experimental conditions, was used. And we used male Wistar rats which were 7 weeks of age and 210-290 g. PPE was extracted with boiling water, and the rats were anesthetized with pentobarbital Na. Their skulls were exposed and a hole was drilled for implantation of a microdialysis probe. In order to increase the recovery of acetylcholine, a probe with a long membrane was used. One day after surgery, the microdialysis probe was perfused with Ringer's solution at a flow rate of 1.5 l/min. The acetylcholine concentration in dialysis samples was measured by high-performance liquid chromatography (HPLC) with electrochemical detection. AChE activity was measured using the radiometric method, as described by Sherman. Results : The comparative effects of PPE and tacrine on hippocampal extracellular acetylcholine concentration was that these cholinesterase inhibitors produced dose-dependent increases in the extracellular acetylcholine concentration. And the effect of PPE and tacrine on rat brain AChE activity was that PPE produced maximal inhibition at 1 h after administration, when AChE activity was 44% of the intact level. AChE activity gradually recovered thereafter, and reached 78% of the intact level at 12 h after administration. Conclusion : In this study, PPE has a potent activity and a long-lasting effect on the central cholinergic system, in terms of the basal concentration of extracellular acetylcholine in the hippocampus and the AChE activity in the brain of rats. And oral administration of PPE increased dose-dependently the basal concentration of extracellular acetylcholine in the hippocampus of rats. PPE may be one of the more useful cholinesterase inhibitors for the treatment of Alzheimer's disease.

• Applied Microscopy
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• v.18 no.1
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• pp.60-76
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• 1988

Chick embryos which have received a single injection of the organophosphate compound, malathion (0.1 mg/0.05 ml, 0.5 mg/0.05 ml, 1.0 mg/0.05 ml or 2.0 mg/0.05 ml) via the yolk sac at certain times (2 days, 4 days or 6 days after incubation) have been investigated. After 9 days of incubation, chick embryos were harvested to examine the effects of malathion on the ultrastructure and the acetylcholinesterase(AChE) activity of the developing spinal cord. The effects of simultaneous injection of malathion and nicotinamide were also compared. On ultrastructural findings, neurons in the ventral horn of spinal cord showed to be inhibited in their differentiation by malathion; nuclear irregularity, separation of nuclear membranes, reduction of ribosomal distribution, and cytoplasmic vacuoles were observed. In the younger embryos treated with relatively high doses of malathion, nucleus and cytoplasmic organelles of neurons were severely destroyed, and the neurons were shown to be necrotic. On cytochemical study of AChE by electron microscope, the positive reaction products of AChE were localized at the membranes of nucleus and endoplasmic reticulum of neurons. Inhibition of AChE activity was severe in groups treated with relatively low doses of malathion. Nicotinamide (5.0 mg/0.05 ml) alleviated malathion-induced morphological alterations. In conclusion, it is suggested that malathion changes the ultrastructure and reduces. AChE activity in differentiating neurons, and the severity of which is consistently dose- and age-dependent.

• Natural Product Sciences
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• v.24 no.4
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• pp.259-265
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• 2018

The three flavone glycosides, 4'-O-methylisoscutellarein 7-O-(6'''-O-acetyl)-${\beta}$-D-allopyranosyl(1${\rightarrow}$2)-${\beta}$-D-glucopyranoside (1), isoscutellarein 7-O-(6'''-O-acetyl)-${\beta}$-D-allopyranosyl(1${\rightarrow}$2)-${\beta}$-D-glucopyranoside (3), and isoscutellarein 7-O-${\beta}$-D-allopyranosyl(1${\rightarrow}$2)-${\beta}$-D-glucopyranoside (4) in addition to a flavonol glycoside, kaempferol 3-O-${\beta}$-D-glucopyranoside (astragalin, 2), were isolated from Stachys japonica (Lamiaceae). In cholinesterase inhibition assay, compound 1 significantly inhibited aceylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities ($IC_{50}s$, $39.94{\mu}g/ml$ for AChE and $86.98{\mu}g/ml$ for BChE). The content of isolated compounds were evaluated in this plant extract by HPLC analysis. Our experimental results suggest that the flavonoid glycosides of S. japonica could prevent the memory impairment of Alzheimer's disease.

• Journal of agriculture & life science
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• v.45 no.6
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• pp.213-226
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• 2011

This study was performed to investigate the effect of essential oils and ethanolic extracts of approximately 650 plant species on acetylcholine esterase (AChE) enzyme activity using Ellman's colorimetric method in 96-well microplates. The results showed that the ethanolic extracts from twig of Sophora subprostrata, twig of Phellodendron amurense, seed of Corylopsis coreana, and essential oil (EO) from Citrus paradisi, Cupressus sempervirens, Ocimum basilicum, Pinus sylvestris and Rosmarinus officinalis inhibited more than 80% of AChE activity. Among these, EO from Pinus sylvestris, C. sempervirens and C paradisi exhibited higher values of AChE inhibitory activity, which were 75, 84 and 99% at a concentration of 50 ug/ml, respectively. Finally, EO from C paradisi (grapefruit, GEO) showed the highest inhibitory activity towards AChE, which showed 91% of inhibition at a concentration of 20 ug/ml. We also examined the anti-dementia effects of GEO in mouse by passive avoidance test and Morris water maze test. The model mouse (male, ICR) of dementia (negative control) was induced by administration of scopolamine (1 mg/kg body weight). The latency time of sample group administrated with GEO (100 mg/kg, p.o.) increased significantly as compared with negative control on passive avoidance test. There were significant recovery from the scopolamine-induced deficits on learning and memory in water maze test through daily administrations with GEO (100 mg/kg, p.o.). From these results, we conclude that GEO treatment might enhance the cognitive function, suggesting that the EO of C. paradis may be a potential candidate for improvement of perceptive ability and dementia.

• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.65-70
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• 2010

The blood-brain barrier (BBB) transport of acetylcholinesterase (AChE) inhibitors, donepezil and tacrine suggested to be mediated by choline transport system in our previous study. Therefore, in the present study, we investigated the interaction of other AChE inhibitors, rivastigmine and galantamine with choline transporter at the BBB. The effects of rivastigmine and galantamine on the transport of choline by conditionally immortalized rat brain capillary endothelial cell lines (TR-BBB cells) were characterized by cellular uptake study using radiolabeled choline. The uptake of [$^3H$]choline was inhibited by rivastigmine and galantamine, with $IC_{50}$ values (i.e. concentration necessary for 50% inhibition) for 1.13 and 1.15 mM, respectively. Rivastigmine inhibited the uptake of [$^3H$]choline competitively with $K_i$ of 1.01 mM, but galantamine inhibited noncompetitively. In addition, the efflux of [$^3H$]choline was significantly inhibited by rivastigmine and galantamine. Our results indicated that the BBB choline transporter may be involved in a part of the influx and efflux transport of rivastigmine across the BBB. These findings should be therapeutically relevant to the treatment of Alzheimer's disease (AD) with AChE inhibitors, and, more generally, to the BBB transport of CNS-acting cationic drugs via choline transporter.

• 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.