• Journal of Microbiology and Biotechnology
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• 제31권7호
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• pp.1022-1027
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• 2021

Three compounds were isolated from marine-derived Streptomyces sp. CNQ-031, and their inhibitory activities against monoamine oxidases (MAOs), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase (BACE-1) were evaluated. Compound 1 (5,7-dihydroxy-2-isopropyl-4H-chromen-4-one) was a potent and selective inhibitor of MAO-A, with a 50% inhibitory concentration (IC₅₀) of 2.70 µM and a selectivity index (SI) of 10.0 versus MAO-B. Compound 2 [5,7-dihydroxy-2-(1-methylpropyl)-4H-chromen-4-one] was a potent and low-selective inhibitor of MAO-B, with an IC₅₀ of 3.42 µM and an SI value of 2.02 versus MAO-A. Compound 3 (1-methoxyphenazine) did not inhibit MAO-A or MAO-B. All three compounds showed little inhibitory activity against AChE, BChE, and BACE-1. The K_i value of compound 1 for MAO-A was 0.94 ± 0.28 µM, and the K_i values of compound 2 for MAO-A and MAO-B were 3.57 ± 0.60 and 1.89 ± 0.014 µM, respectively, with competitive inhibition. The 1-methylpropyl group in compound 2 increased the MAO-B inhibitory activity compared with the isopropyl group in compound 1. Inhibition of MAO-A and MAO-B by compounds 1 and 2 was recovered by dialysis experiments. These results suggest that compounds 1 and 2 are reversible, competitive inhibitors of MAOs and can be considered potential therapies for neurological disorders such as depression and Alzheimer's disease.

• Biomolecules & Therapeutics
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• 제18권1호
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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 Acupuncture Research
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• 제21권3호
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• pp.235-248
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• 2004

It has been investigated about aging theory. However, aging mechanism still remains to be unknown. Aging and aging related diseases might be due to oxidative damage and these were modifiable by genetic and environmental factors. For designing an optimal medical treatment and countermeasure against aging and aging related disease, it is necessary to understand the aging mechanism. Acetylcholine(Ach) plays an important role in memory. If someone doesn't have enough Ach, he has a tendency to catch a Alzheimer's disease. Corydalis tuber has been clinically used to treat heart disease, gastrointestinal disease and other diseases including endocrine disease in Oriental medicine. The purpose of this article is to investigate the inhibitory effect on Acetylcholinesterase and scavenging effects on NO, DPPH of Corydalis tuber Acua-acupuncture solution(CTAS). The results are summerised as follows; 1. There is a significant inhibitory effect of $0.01mg/m{\ell}$ CTAS group at 20, 30, 60 minutes and $0.1mg/m{\ell}$ CTAS group at 10, 20, 30, 60 minutes on AchE. 2. There is no significant scavenging effect of CTAS on NO. 3. There is a significant scavenging effect of $0.1mg/m{\ell}$ and $0.01mg/m{\ell}$ CTAS group at 10 minutes but there is no significant scavenging effect at 20, 30, 60 minutes on DPPH. There is a significant scavenging effect of $1mg/m{\ell}$ CTAS group at 10, 20, 30, 60 minutes on DPPH.

• Applied Biological Chemistry
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• 제42권4호
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• pp.336-343
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• 1999

담자균류로부터 치매 예방 및 치료 효과를 갖는 생물활성물질을 탐색하기 위한 기초 자료를 확립하기 위하여 56종의 배양 균사체 메탄을 추출물 및 배양 여액의 ethylacetate(EtOAc) 가용성 분획에 대하여 prolylendopeptidase(PEP), acetylcholine esterase(AChE) 및 혈전 응고에 대한 저해활성을 측정하였다. 그 결과 PEP에 대하여 Amanita aspera, Phellinus chrysoloma의 균사체 추출물 및 배양여액의 EtOAc 가용성 분획이 40ppm에서 모두 90% 이상의 저해활성을 나타내었으며 분홍껍질고약버섯(Peniophora quercina), 잎새버섯(Grifola frondosa), Wolfiporia extensa, 좀나무싸리버섯(Clavicorona pyxidata) 및 Phanerochaete soy교교의 배양액이 90% 이상의 저해활성을 나타내었다. AChE에 대하여는 40ppm 농도에서 어느 것도 강한 활성을 나타내지 못하였으나 조개껍질버섯(Lenzites betulina), Phellinus chrysoloma, Wolfiporia extensa, Phanerochaete sordida의 균사체 추출물과 Hypocrea nigricans, Coriolus azureus, 팽나무버섯(Flammuzina velutipes), Phlebiopsis gigantea 및 Bondarzewia montana의 배양여액 EtOAc 가용성 분획이 40% 정도의 저해활성을 나타내었다. 한편 혈전응고 저해활성의 지표로 삼은 thrombin times(TT) assay에서는 Amanita aspera, Oxyporus latemarginata, 분홍껍질고약버섯(Peniophora quercina), 말굽버섯(Fomes fomefarius)의 배양여액 EtOAc 추출물과 Clitocybe clavipes, Trametes versicolor, Phlebiopsis gigantea의 균사체 추출물이 550 ppn의 농도에서 혈전 생성에 걸리는 시간을 2배 내지 3배 연장하는 효과를 나타내었으나 activated partial thromplastin times(APTT) assay에서는 어느 것도 효과를 인정할 수 없었다.

• 한국수산과학회지
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• 제49권2호
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• pp.131-136
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• 2016

Marine organisms are sources of many bioactive compounds, such as essential fatty acids, essential amino acids, vitamins, and minerals, making them useful candidates for the production of safe bioactive substances. They also synthesize glutamic acid, which can be used to produce γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system (CNS), via fermentation with Lactobacillus brevis BJ-20. This study investigated the degree to which fermented sea tangle (FST) inhibits enzymes such as acetylcholine esterase (AChE) and prolyl endopeptidase (PEP) and affects memory of normal mice using the T-maze test. FST inhibited more than 90% of AChE at 1 mg/mL and 50% of PEP at 8 mg/mL. Oral FST (100 mg/kg) significantly improved performance of normal mice on the T-maze. Therefore, sea tangle fermented with L. brevis BJ20 effectively contributes to memory improvement and might be a useful functional food ingredient.

• 농약과학회지
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• 제9권1호
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• pp.97-101
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• 2005

피라졸 계통의 유기인계 살충제인 flupyrazofos(O,O-diethyl O-1-phenyl-3-trifluoromethylpyrazo-5-yl phosphorothioate)의 합성공정에서 생산된 원제 1(95.4%), 원제 2(97.6%) 그리고 정제품(99.2%)에 대한 불순물 조성과 함량을 조사하였으며, 이들 원제 및 정제품을 이용하여 in vitro와 in vivo 상에서 acetylcholinesterase (AChE) 활성 저해 정도를 비교 검정하였다. 실험결과 불순물의 조성은 O,O,O-triethylthio-phosphoric acid (TEA), 1-phenyl-3-trifluoromethyl-5-ethoxy pyrazole(PTMEP), O,O-diethyl O-1-phenyl-3-trifluoromethylpyrazo-5-yl phosphoric acid ester(flupyrazofos oxon), O,S-diethyl O-1-phenyl-3-trifluoromethylpyrazo-5-yl phosphorothionate (S-ethyl flupyrazofos)이었으며, 이들 불순물들의 함량이 원제 중에서 전반적으로 높았다. In vitro 상에서 AChE 저해는 불순물들이 많은 원제 1에서 가장 빠르게 저해되었으며, 생쥐 뇌 AChE (in vivo)에 대한 $I_{50}$ 값은 원제 1과 2가 정제품 보다 40% 이상 높았다. 이는 정제품에 비하여 원제 중에 더 많이 함유된 flupyrazofos oxen과 S-methyl flupyrazofos에 의한 영향일 것으로 판단되었다.

• 대한한의학회지
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• 제39권3호
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• pp.1-16
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• 2018

Objectives: The purpose of this study was to investigate the effects of 56 herbal formulae covered by the National Health Insurance Corporation (NHIC) on dementia-related biomarkers and neuronal cell changes. Methods: The 56 herbal formulae were extracted with 70% ethanol at $100^{\circ}C$ for 2 h. The antioxidant properties was measured by radical scavenging assay using ABTS+ radical. The acetylcholinesterase (AChE) activity was tested by Ellman's assay and $amyloid-{\beta}$ ($A{\beta}$) aggregation was determined using fluorescence method. To estimate the inhibitory effects of herbal formulae on neuronal cell death and inflammation using HT22 hippocampal cells and BV-2 microglia, respectively. Results: Among the 56 herbal formulae, Dangguiyukhwangtang, Banhasasimtang, Samhwangsasimtang, Cheongwiesan, Hwangryunhaedoktang, Banhabaekchulchunmatang, Jaeumganghwatang, Cheongseoikgitang, and Hoechunyanggyuksan has a significant inhibitory effects on acetylcholinesterase (AChE) activity. Doinseunggitang and Samhwangsasimtang exerted the effect on the inhibition of $amyloid-{\beta}$ ($A{\beta}$) aggregation. Additionally, 10 herbal formulae affected AChE and $A{\beta}$ aggregation revealed antioxidant activity as well as neuroprotective and anti-neuroinflammation effects in neuronal cell lines. Conclusions: 10 herbal formulae that have been shown to be effective against the major dementia markers have been shown to have antioxidant activity, neuronal cell protection and inhibition of brain inflammation. Further investigation of these herbal formulae will need to be validated in dementia animal models.

• 대한본초학회지
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• 제34권4호
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• pp.9-18
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• 2019

Objectives : It has been known to be correlated between phlegm and dementia from the perspective of oriental medicine, but it is unexplored whether herbal medicines to treat phlegm have pharmacological actions on Alzheimer's disease (AD). The aim of this study was to evaluate and to compare effects of herbal medicines to treat phlegm against AD in vitro. Methods : We selected 11 herbal medicines which treat phlegm and obtained each extract by boiling in 10-fold distilled water for 2 h. And we performed the assay of acetylcholinesterase (AChE) inhibitory effects of 11 herbal extracts. Next, we evaluated neuroprotective effects of them against amyloid $beta_{25-35}$ ($A{\beta}_{25-35}$) plaque-induced toxicity in HT22 mouse hippocampal neuronal cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. To investigate whether they show the anti-inflammatory effects against lipopolysaccharide (LPS), we also measured the levels of nitric oxide (NO) in BV2 microglia cells using griess reagent assay. Results : We found that Gamiyeongsin-hwan (GYH) and Cheonghunhwadam-tang (CHT) exhibited remarkable AChE inhibitory effects. In HT22 cells, Arisaematis Rhizoma, Trichosanthis Semen and Fritillariae Thunbergii Bulbus suppressed $A{\beta}_{25-35}$ plaque-induced neuronal cell death. In BV2 cells, Cheongung-hwan significantly inhibited the increase of NO contents induced by LPS and GYH and CHT showed a tendency to inhibit LPS-induced NO generation. Conclusions : These results suggest that several herbal medicines to treat phlegm showed the significant effects on AChE inhibition, neuroprotection against $A{\beta}_{25-35}$ plaque-induced toxicity, and inhibition of NO generation. Therefore, we demonstrate the possibility that herbal medicines with treating phlegm has effects against AD.

• 동의신경정신과학회지
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• 제17권1호
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• pp.59-78
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• 2006

Objective : This research investigates the effect of the CMT and SCMT on Alzheimer's disease. Methods : The effects of the CMT and SCMT on (1) amyloid precursor proteins(APP), acetylcholinesterase(AChE) mRNA of PC-12 cells treated with CT-105; (2) the AChE activity and the APP production of PC-12 cell treated with CT-105; (3) the behavior; (4) expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA; (5) the infarction area of the hippocampus in Alzheimer's disease mice induced with CT105 & ${\beta}A$ were investigated Rresults : 1. The CMT and SCMT suppressed the expression of APP, AChE mRNA in PC-12 cells treated with CT-105 2. The CMT and SCMT suppressed the AChE activity, and the production of APP significantly in PC-12 cells treated with CT-105. 3. For the CMT and SCMT group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by ${\beta}A$ in the Morris water maze experiment, which measured stop-through latency, and distance movement-through latency 4. The CMT and SCMT suppressed the over-expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA in the mice with Alzheimer's disease induced by ${\beta}A$. 5. The CMT and SCMT reduced the infarction area of hippocampus with Alzheimer's disease induced by ${\beta}A$. Conclusions : These results suggest that the CMT and SCMT may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the CMT and SCMT for Alzheimer's disease is suggested for future research.

• 한국약용작물학회지
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• 제25권6호
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• pp.353-360
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• 2017

Background: A critical features of Alzheimer's disease (AD) is cognitive dysfunction, which partly arises from decreased in acetylcholine levels. AD afftected brains are characterized by extensive oxidative stress, which is thought to be primarily induced by the amyloid beta ($A{\beta}$) peptide. In a previous study, Cinnamomum loureiroi tincture inhibited acetylcholinesterase (AchE) activity. That study identified AChE inhibitor in the C. loureiroi extract. Furthermore, the C. loureiroi extract enhanced memory in a trimethyltin (TMT)-induced model of cognitive dysfunction, as assessed via two behavioral tests. Rosa laevigata extract protected against oxidative stress-induced cytotoxicity. Administrating R. laevigata extracts to mice significantly reversed $A{\beta}$-induced learning and memory impairment, as shown in behavioral tests. Methods and Results: We conducted behavioral to examine the synergistic effects of C. loureiroi and R. laevigata extracts in inhibiting AChE and counteracting TMT-induced learning and memory losses. We also performed biochemical assays. The biochemical results showed a relationship between increased oxidative stress and cholinergic neurons damage in TMT-treated mice. Conclusions: A diet containing C. loureiroi and R. laevigata extracts ameliorated learning and memory impairments in the Y-maze and passive avoidance tests, and exerted synergistic inhibitory effect against AChE and lipid peroxidation.