• Natural Product Sciences
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• 제25권2호
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• pp.115-121
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• 2019

Alzheimer's disease is a chronic neurodegenerative disorder with no curative treatment. The commercially available drugs, which target acetylcholinesterase, are not satisfactory. The aim of this study was to investigate the cholinesterase inhibitory activity of Solenostemma argel aerial part. Eight compounds were isolated and identified by NMR: kaempferol-3-O-glucopyranoside (1), kaempferol (2), kaempferol-3-glucopyranosyl($1{\rightarrow}6$)rhamnopyranose (3) p-hydroxybenzoic acid (4), dehydrovomifoliol (5), 14,15-dihydroxypregn-4-ene-3,20-dione (6), 14,15-dihydroxy-pregn-4-ene-3,20-dione-$15{\beta}$-D-glucopyranoside (7) and solargin I (8). Two of them (compounds 2 and 3) could inhibit over 50 % of butyrylcholinesterase activity at $100{\mu}M$. Compound (2) displayed the highest inhibitory effect against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with a slight selectivity towards the latter. Molecular docking studies supported the in vitro results and revealed that (2) had made several hydrogen and ${\pi}-{\pi}$ stacking interactions which could explain the compound potency to inhibit AChE and BChE.

• 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.

• 생약학회지
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• 제48권3호
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• pp.243-247
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• 2017

To find the anti-Alzheimer's activity of Cacalia hastata var. orientalis (Compositae), caffeoylquinic acids were analyzed in this plant by HPLC and the inhibitory activities of the extract on cholinesterases including acetylcholinesterase (AChE) and butyrylcholinesterse (BChE) and peroxynitrite ($ONOO^-$) were assayed. Sum of caffeoylquinic acids in the 80% MeOH extract was quantitatively higher in leaves (35.8% of the extract) than in stems (3.7%). The compound, 3,5-dicaffeoylquinic acid, was contained in the highest amount in the leaf (44.32 mg/g dry weight). The $IC_{50}s$ of the 80% MeOH extract were shown to be $67.45{\mu}g/ml$ for AChE, and $8.59{\mu}g/ml$ (for $ONOO^-$), respectively, suggesting that the leaves would have the anti-Alzheimer's activity due to the high content of caffeoylquinic acids.

• 산업식품공학
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• 제15권4호
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• pp.289-296
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• 2011

Twenty four fractions by solvent extraction and/or acid precipitation from fruit body and culture broth of Inonotus obliquus were prepared, and their inhibitory effect against acetylcholinesterase (AChE) was investigated. Among these fractions, acid (1 M HCl) precipitates from cell-free culture broth and fruit body exhibited the highest inhibitory effect on AChE in vitro. Acid precipitates inhibited AChE activity in a concentration-dependant manner and $IC_{50}$ values of both acid precipitates were 0.53 mg/mL. The inhibition pattern was general non-competitive inhibition. The energetic parameters were also determined by dual substrate/temperature design. Both acid precipitates increased the values of Ea, ${\Delta}H,/;{\Delta}G$ and ${\Delta}H^{\ast}$ decreasing the value of ${\Delta}S$ for AChE. The results implied that the acid precipitates from I. obliquus increased the thermodynamic barrier, leading to the breakdown of ES complex and the formation of products as inhibitory mechanism.

• Archives of Pharmacal Research
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• 제27권1호
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• pp.53-56
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• 2004

In the course of finding Korean natural products with acetylcholinesterase (AChE) inhibitory activity, we found that a methanolic extract of the twigs of Vaccinium oldhami significantly inhibited AChE. Bioassay-guided fractionation of the methanolic extract resulted in the isolation of two compounds, taraxerol (1) and scopoletin (2), as active constituents. These compounds inhibited AChE activity in a dose-dependent manner, and the $IC_{50}$/ values of compounds 1 and 2 were 33.6 (79 $\muM$) and 10.0 (52 $\muM$) $\mu$g/mL, respectively.

• 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.

• 한국식품저장유통학회지
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• 제19권5호
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• pp.751-756
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• 2012

건조 오배자를 80% MeOH로 침지 추출하여 얻어진 추출물에 대해 n-hexane, EtOAc 및n-BuOH로 순차 용매 분획하였고, 얻어진 결과물에 대하여 DPPH 및 $ABTS^+$ radical 소거능 및 AChE 저해활성을 평가하였다. DPPH 라디칼 소거능은 총 페놀성 화합물의 함량이 상대적으로 높은 EtOAc층에서 $IC_{50}$값이 $10.4{\pm}0.3mg/mL$으로 대조군인 (+)-catechin과 비교하였을 때 우수한 라디칼 소거능을 확인하였고, 오배자 추출물에 존재하는 총 페놀성 화합물의 함량과 라디칼 소거능과의 연관성을 시사하였다. 또한 $ABTS^+$ 라디칼 소거능은 EtOAc층이 $IC_{50}$값이 7.8 mg/mL 이하였고, n-BuOH층이 $IC_{50}=8.5{\pm}0.9mg/mL$으로 상대적으로 우수한 활성이 확인 되었으며, 이는 우수한 활성물질의 존재가 시사되었다. 또한, AChE 저해활성을 측정한 결과, 우수한 $ABTS^+$ 라디칼 소거능을 나타낸 EtOAc층의 $IC_{50}$은 각각 31.3 mg/mL 이하의 저해율을 나타내었으며 이는 대조군인 tacrine에 비해 다소 낮으나 분획물일 때의 활성임을 감안할 때 단일물질로 정제할 경우 더욱 우수한 효능의 화합물이 존재할 가능성을 시사하였다. 향후 이들 활성물질 동정을 통한 활성 기작에 대한 연구가 필요하며 본 연구결과는 천연물유래의 우수한 라디칼 소거능 및 AChE 저해능을 가지는 새로운 선도화합물 발굴을 위한 기초자료로 이용될 수 있을 뿐만 아니라 오배자의 식물 화학적 성분연구에 대한 기초자료로 활용가능하리라 사료된다.

• Mycobiology
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• 제38권1호
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• pp.52-57
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• 2010

To develop a potent anti-obesity lipase inhibitor from mushroom, the lipase inhibitory activities of various mushroom extracts were determined. Methanol extracts from Phellinus linteus fruiting body exhibited the highest lipase inhibitory activity (72.8%). The inhibitor was maximally extracted by treatment of a P. linteus fruiting body with 80% methanol at $40^{\circ}C$ for 24 hr. After partial purification by systematic solvent extraction, the inhibitor was stable in the range of $40\sim80^{\circ}C$ and pH 2.0~9.0. In addition to lipase inhibitory activity, the inhibitor showed 59.4% of superoxide dismutase-like activity and 56.3% of acetylcholinesterase inhibitory activity.

• KSBB Journal
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• 제28권6호
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• pp.372-379
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• 2013

This study was to investigate the chemical properties and nitrite scavenging and acetylcholinesterase inhibitory activities from Salicornia herbaciea seed. The lactic acid content of seed was about 2.0 fold higher than that of stem. Among various free sugars, the maximum fructose of seed, glucose of stem, and mannose contents of root were obtained, 176.3, 125.6, and 112.8 mg/100g, respectively. The maximum leucine content of seed among the essential amino acid was obtained, 853.7 mg/100g, which was about 3.0 or 6.0 folds higher than that of root or stem. In the case of glutamic acid of seed, it was 2,388.7 mg/100g, which was 5.6 or 9.8 folds higher han that of root or stem. The ratio of essential amino acid and total amino acid of seed was 30.14%. The ${\gamma}$-aminobutyric acid contents of seed, stem, and root were 43.87, 23.88, and 27.8 mg/100g, respectively. The catechin content of seed was an order of epigallocatechin (723.2 mg/100g) > epigallocatechingallate (654.3 mg/100g) > epicatechin (443.5 mg/100g) > gallocatechin (314.1 mg/100g). Especially, the non-gallated catechins content was about 2.0 folds higher than that of gallated catechins content. The nitrite scavenging activity of seed increased from 38.7 to 65.9% when the hot-water extract content of seed at pH 1.2 increased from 1.0 to 5.0 mg/mL. However, it was decreased to 25.7% at pH 6. The acetylcholinesterase inhibitory activity of seed was increased from 13.2 to 44.6% when the extract content increased from 20 to 100 mg/mL. These results show that S. herbaciea seed has a good potential to be used as a source of material or additive in cosmetics, food, and drug compositions.

• 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.