• 생명과학회지
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• 제29권2호
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• pp.173-180
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• 2019

Amyloid ${\beta}$-단백질($A{\beta}$)은 알츠하이머 질병의 특징인 노인성 반점의 주요 성분이며 in vivo와 in vitro에서 신경세포를 대상으로 독성효과를 유발한다. 항산화물질과 프로테오글리칸을 포함한 많은 환경인자들에는 $A{\beta}$의 독성을 완화하는 물질들이 존재한다. 특히, 천연물질들 중에서 자신은 독성이 없으며, 알츠하이머 환자에게 치료효능을 나타내는 천연화합물들을 순수 분리하는 것은 매우 가치가 있다. 본 연구에서는 소엽맥문동의 메탄올 추출물로부터 에틸아세테이트 유기용매로 분획한 물질(OJEA)을 대상으로 in vitro상에서 신경세포독성 제어효능을 탐색하였다. 본 실험을 위해 PC12 세포주에 $A{\beta}_{25-35}$로 유발한 독성에 대한 OJEA 분획물의 억제효능을 MTT 환원법 분석으로 측정하였으며, ${\beta}$-secretase 활성에 대한 OJEA 분획물의 억제효능을 세포기반 ${\beta}$-secretase assay system으로 측정하였다. 또한 PC12 세포에서 $A{\beta}_{25-35}$에 의해 유도된 산화적 스트레스에 대한 OJEA 분획물의 억제효과를 지질과산화 분석법으로 수행하였다. 본 연구의 결과는 OJEA 분획물이 PC12 세포에서 $A{\beta}_{25-35}$에 의해 유도된 세포독성을 강하게 예방 또는 억제하는 효과가 있음을 확인하였으며, 또한 ${\beta}$-secretase의 활성을 억제함으로써 $A{\beta}$의 생성을 완화하는 효과를 예상할 수 있었다. OJEA 분획물은 또한 PC12 세포에서 $A{\beta}_{25-35}$에의 노출에 의하여 유도되는 malondialdehyde (MDA)의 생성을 강하게 억제하였다. 결론적으로, 본 연구의 결과에 의하면 OJEA 분획물에는 $A{\beta}$ 독성에 대한 신경세포의 보호효능을 함유하는 생리활성물질이 함유되어 있음을 제시한다.

• Archives of Pharmacal Research
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• 제28권7호
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• pp.799-803
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• 2005

In the course of screening anti-dementia agents from natural products, two $\beta$-secretase (BACE1) inhibitors were isolated from the ethyl acetate soluble fraction of Sanguisorbae Radix by the activity-guided purification using silica gel, Sephadex LH-20, and RP-HPLC. They were identified as 1,2,3-trigalloyl-4,6-hexahydroxydiphenoyl-$\beta$-D-glucopyranoside (Tellimagrandin II, 1) and 1,2,3,4,6-pentagalloyl-$\beta$-D-glucopyranoside (2) and were shown to non-competitively inhibit $\beta$-secretase (BACE1) with the $IC_{50}$ values of $3.10{\times}10^{-6}M\;and\;3.76{\times}10^{-6}M$, respectively. The Ki values of 1 and 2 were $6.84{\times}10^{-6}M\;and\;5.13{\times}10^{-6}M$. They were less inhibitory to asecretase (TACE) and other serine proteases such as chymotrypsin, trypsin, and elastase, suggesting that they were relatively specific inhibitors of BACE1.

• 생명과학회지
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• 제19권5호
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• pp.688-691
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• 2009

The methanol extract of muskmelon (Cucumis melo) has been investigated for its cognition enhancing effects by evaluation of inhibitory activities on acetylcholinesterase, a degrading enzyme of acetylcholine, a brain neurotransmitter, and ${\beta}$- secretase, which forms the ${\beta}$-amyloid toxic protein from its precursor protein. A passive avoidance task, one of the animal model experiments for learning and memory, was also performed. As a result, the melon extract showed 15.8% and 35.3% inhibition on acetylcholinesterase and ${\beta}$-secretase, respectively, with a final concentration of 100 mg/ml. In the animal model test, melon extract significantly (p<0.05) lengthened the step-through latency time by 22.7% compared to the control group, suggesting that melon extract has, indeed, an effect on cognition enhancement.

• 한국균학회지
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• 제40권4호
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• pp.229-234
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• 2012

알츠하이머병(Alzheimer's disease, AD) 의 진행과정의 주요 분자는 베타아밀로이드 펩타이드(${\beta}$-amyloid peptide, $A{\beta}$)이며, $A{\beta}$ 생성에 가장 중요한 작용을 하는 효소가 ${\beta}$-secretase이다. 본 연구에서는 상황버섯 자실체로부터 수용성 고분자물을 분리, 정제하였고, 이들 고분자물이 주로 glucose, galactose, mannose 등으로 구성되어 있고, 특히, glucose 함량이 가장 많은 glucan의 일종으로서, FT-IR 구조분석, laminarinase 효소분석에 의한 결합구조 분석 등의 결과로부터, 최소한 일정 부분 beta-(1,3)-결합구조를 갖는 beta-glucans 들의 일종이고, beta-(1,6)-결합의 분지를 갖는 beta-(1,3)(1,6)-glucan은 아닌 beta-(1,3)-glucans임을 확인하였다. Et-P는 분자량이 각각 1,629, 1,294, 21 kDa인 다당류들로서, FT-IR 분석과 원소분석의 결과로 볼 때, Et-P가 페놀성(phenolic) 물질과 복합체 형태로 존재하는 다당류일 것으로 판단되었다. 상황버섯 자실체 열수 추출물로부터 분리된 수용성 다당류인 Et-P는 DPPH radical 소거능을 보이고, 특히, 뇌신경세포 사멸에 의한 치매 유발 물질로 알려진 베타-아밀로이드 펩타이드($A{\beta}$)를 생성하는 ${\beta}$-secretase 효소의 활성을 현저히 저해하는 효과를 나타냈다. 이는 상황버섯 자실체 유래 수용성 다당류인 Et-P가 향 후 보다 심도 깊은 연구를 통해 항치매 효과를 나타내는 건강 식의약소재로 개발될 가능성이 있음을 보였다.

• 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.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.271.2-271.2
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• 2003

The ${\gamma}$- and ${\beta}$-secretase are one of the most important proteases, which cleave amyloid precursor protein (APP) into neurotoxic A${\beta}$ peptide in Azheimer's type dementia. In the course of screening for anti-dementia agents from natural products, the mycelial culture of mushroom Phellinus linteus showed potent inhibition againt ${\beta}$-secretase (BACE1). (omitted)

• Biomolecules & Therapeutics
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• 제27권3호
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• pp.276-282
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• 2019

${\beta}$-amyloid precursor protein (APP) can be cleaved by ${\alpha}$-, and ${\gamma}$-secretase at plasma membrane producing soluble ectodomain fragment ($sAPP{\alpha}$). Alternatively, following endocytosis, APP is cleaved by ${\beta}$-, and ${\gamma}$-secretase at early endosomes generating ${\beta}$-amyloid ($A{\beta}$), the main culprit in Alzheimer's disease (AD). Thus, APP endocytosis is critical for $A{\beta}$ production. Recently, we reported that Monsonia angustifolia, the indigenous vegetables consumed in Tanzania, improved cognitive function and decreased $A{\beta}$ production. In this study, we examined the underlying mechanism of justicidin A, the active compound of M. angustifolia, on $A{\beta}$ production. We found that justicidin A reduced endocytosis of APP, increasing $sAPP{\alpha}$ level, while decreasing $A{\beta}$ level in HeLa cells overexpressing human APP with the Swedish mutation. The effect of justicidin A on $A{\beta}$ production was blocked by endocytosis inhibitors, indicating that the decreased APP endocytosis by justicidin A is the underlying mechanism. Thus, justicidin A, the active compound of M. angustifolia, may be a novel agent for AD treatment.

• Food Science and Biotechnology
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• 제15권4호
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• pp.617-624
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• 2006

Various plant phenolics were assessed for (${\beta}$-secretase (BACE1) inhibitory activity in order to screen for anti-dementia agents. Among 39 phenolics, eight compounds, 1,2,3-trigalloyl glucopyranoside, acetonyl geraniin, euphorscopin, furosine, helioscopinin A, helioscopinin B, jolkinin, and rugosin E exhibited strong inhibition of BACE1 with $IC_{50}$ values of $5.87{\times}10^{-8}-54.93{\times}10^{-6}\;M$. Among them, rugosin E was the most potent ($IC_{50}$ $5.87{\times}10^{-8}\;M$). The active compounds were shown to be non-competitive inhibitors by Dixon plot. All the phenolic BACE1 inhibitors except furosin also suppressed prolyl endopeptidase (PEP) activity. However, these phenolic compounds caused less inhibition of ${\alpha}$-secretase (tumor necrosis factor a converting enzyme; TACE) and no significant inhibition of other serine proteases such as trypsin, chymotrypsin, and elastase was seen, demonstrating that they are relatively specific to both BACE1 and PEP. No significant structure-activity relationships were found.

• Bulletin of the Korean Chemical Society
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• 제27권9호
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• pp.1371-1376
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• 2006

BACE 1 ($\beta$-secretase), a membrane bound aspartic protease, is a key enzyme in the process of amyloid precursor protein (APP) into A$\beta$ peptide which is considered to play a causative role in Alzheimers Disease (AD). Here, we reported the synthesis and inhibitory activity of optically active 3-amino-4-aryl-piperidines.

• 생약학회지
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• 제46권4호
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• pp.327-333
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• 2015

Alzheimer's disease (AD) is a progressive neurodegenerative disorder symptomatically characterized by impairment in memory and cognitive abilities. AD is characterized pathologically by the deposition of ${\beta}$-amyloid ($A{\beta}$) peptides of 40-42 residues, which are generated by processing of amyloid precursor protein (APP). $A{\beta}$ has been believed to be neurotoxic and now is also considered to have a role on the mechanism of memory dysfunction. In this study, we tested that EtOH extract of the fruits of Chaenomeles sinensis Koehne (CSE) affects on the processing of APP from the APPswe over-expressing Neuro2a cell line. We found that CSE increased over 2 folds of the $sAPP{\alpha}$ secretion level, a metabolite of ${\alpha}$-secretase. We showed that CSE reduced the secretion level of $A{\beta}42$ and $A{\beta}40$ by down regulation of ${\beta}$-secretase (BACE) without cytotoxicity. Furthermore, we found that CSE inhibited BACE and acetylcholinesterase activity in vitro. We suggest that Chaenomelis Fructus may be an useful source to develop a herbal medicine for AD.