• 한국식품영양과학회지
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• 제32권7호
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• pp.971-975
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• 2003

우리나라가 고령화사회에서 고령사회로, 고령사회에서 초고령사회로 도달하는 시간이 각각 22년과 10년으로 추정되며 선진국에 비해 진입속도가 빠를 것으로 보고 있다. 고령화인구에 따라 일상생활은 물론 지역 사회에서의 활동, 더 나아가서는 직업 활동을 할 수 없는 기억 장애현상인 노인성 치매가 더욱 문제시된다. 따라서 본 연구에서는 우리나라에서 정신건강 관련하여 이미 이용되고 있거나 민간에서 구두로 알려진 식품 총 100종을 선정하고, 메탄올 추출물에 대하여 prolyl endopeptidase에 대한 활성 저해율을 측정하였다. 그 결과, 40ppm 농도에서 도토리가 96.0%로 가장 높은 활성 저해율을 보였고, 산딸기가 92.0%, 호두가 73.0%로 나타났으며, 그 외의 나머지 식품들은 56.1%인 녹차를 제외하고는 모두 50% 미만의 수준이었다. 본 연구결과 PEP에 비교적 특이적으로 작용하는 저해제로서 도토리와 산딸기를 확인할 수 있었고, 현재까지 개발되고 보고된 합성 peptide인 PEP저해제와는 달리 천연식품이란 점에서, 앞으로 이 식품들이 항치매 예방 기작 구명에 유용하게 이용됨과 동시에 치매의 예방을 위한 기능성 식품으로서 이용될 수 있을 것으로 기대된다.

• Applied Biological Chemistry
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• 제43권2호
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• pp.158-161
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• 2000

• Journal of Applied Biological Chemistry
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• 제48권4호
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• pp.207-212
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• 2005

Prolyl endopeptidase (PEP, EC 3.4.21.26), also referred to as prolyl oligopeptidase, has been suggested to participate in learning and memory processes by cleaving peptide bonds on carboxyl side of prolyl residue within neuropeptides of less than 30 amino acids, and is abundant in brains of amnestic patients. Therefore, compounds possessing PEP inhibitory activity can be good candidate of drug against memory loss. Upon examination for PEP inhibition from traditional medicinal plants having tonic, stimulating, and anti-amnestic effects, Corni Fructus (Cornus officinallis) showed significant PEP inhibition. Ursolic and oleanolic acids, components of Corni Fructus, inhibited PEP with $IC_{50}$ values of $17.2\;{\pm}\;0.5$ and $22.5\;{\pm}\;0.7\;{\mu}M$, respectively.

• Archives of Pharmacal Research
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• 제26권12호
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• pp.1024-1028
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• 2003

A prolyl endopeptidase inhibitor was isolated from the ethyl acetate soluble fraction of Phyllanthus ussurensis. The active compound was identified as an ellagitannin, corilagin. It was shown to non-competitively inhibit prolyl endopeptidase (PEP) with the $IC_{50}$ value of $1.17 \times $10^{-6}\mu$M. The Ki value was $6.70 \times 10^{-7}$ M. Corilagin was less inhibitory to other serine proteases such as chymotrypsin, trypsin, and elastase, indicating that it was relatively a specific inhibitor of PEP. Corilagin also effectively inhibited reactive oxygen species such as hydroxide and superoxide anion radical, hydrogen peroxide, and DPPH. Especially, corilagin showed potent scavel1ging activity on the superoxide anion radical in the ESR method ($IC_{50} =3.79 \times 10^{-6}$M) as well as xanthine oxidase system.

• 생약학회지
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• 제30권3호
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• pp.231-237
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• 1999

About forty sea weeds were screened for their inhibitory effects against prolyl endopeptidase, tyrosinase and thrombus coagulation. Out of them, methanolic extract of Ecklonia cava, Sargassum patens, Sargassum hemiphyllum, Sargassum thunbergii, Sargassum singgildianum, Hizikia fusiformis, and Ishige okamurae inhibited more than 90% of prolyl endopeptidase activity at 40 ppm. Sargassum siliquastrum and Ecklonia cava exhibited 51% and 76% of inhibitory activity against tyrosinase at 40 ppm, respectively. In APTT assay system, Sargassum singgildianum, Pterocladia capilacea and Hizikia fusiformis delayed coagulation of thrombus about two times (210, 211, and 198% over control at ca 367 ppm, respectively) and in TT assay, Lomentaria catenata, Laurencia okamurae, and Hizikia fusiformis did most effectively (216,197, and 251% at ca 367 ppm, respectively).

• Journal of Applied Biological Chemistry
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• 제49권3호
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• pp.110-113
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• 2006

Prolyl endopeptidase (PEP, EC 3.4.21.26, also referred to as prolyl oligopeptidase) degrades proline containing, biologically active neuropeptides such as vasopressin, substance P and thyrotropin-releasing hormone by cleaving peptide bonds on carboxyl side of prolyl residue within neuropeptides of less than 30 amino acids. Evaluation of PEP levels in postmortem brains of Alzheimer's disease patients revealed significant increases in PEP activity. Therefore, a specific PEP inhibitor can be a good candidate of drug against memory loss. Upon our examination for PEP inhibitory activity from micronutrients, ascorbic acid (vitamin C) showed small but significant PEP inhibition (13% PEP inhibition at $8{\mu}g{\cdot}ml^{-1}$). Palmitic acid showed almost no PEP inhibition. However, 6-O-palmitoyl ascorbic acid ($\underline{1}$) showed 70% PEP inhibition at $8{\mu}g{\cdot}ml^{-1}$ indicating that hydrophobic portion of the compound $\underline{1}$ may facilitate the inhibitory effect. $IC_{50}$ value of compound $\underline{1}$ was $12.6{\pm}0.2{\mu}M$. The primary and secondary Lineweaver Burk and Dixon plots for compound $\underline{1}$ indicated that it is a non-competitive inhibitor with inhibition constant (Ki) value of $23.7{\mu}M$.

• Journal of Applied Biological Chemistry
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• 제56권3호
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• pp.183-185
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• 2013

Two styrylpyranones (1 and 2) were isolated from the $CH_2Cl_2$-soluble fraction of Phellinus linteus and their structures were established by extensive Nuclear magnetic resonance (NMR) spectral data as inoscavin E and C. Both compounds showed significant prolyl endopeptidase inhibitory activity with $IC_{50}$ values of $4.26{\pm}0.14$ and $4.08{\pm}0.04{\mu}M$ and $K_i$ values of $1.50{\pm}0.02$ and $1.43{\pm}0.03{\mu}M$, respectively. They also exhibited antioxidant capacities against the ABTS radical system with $EC_{50}$ values of $6.47{\pm}0.05$ and $7.64{\pm}0.06{\mu}M$, respectively.

• Archives of Pharmacal Research
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• 제21권2호
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• pp.207-211
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• 1998

Three prolyl endopeptidase inhibitors were isolated and identified as luteolin, quercetin and ${\beta}$-sitosterol-3-O-${\beta}$-D-glucopyranoside with $IC_{50}$ of 0.17, 0.19 and 27.5 ppm, respectively. The inhibition of two flavonoids were non-competitive with substrate. Twenty authentic flavonoids were tested in order to investigate structure-activity relationship. No significant relationship was found in them, however, catechol moiety of B-ring and 7-OH group in flavonoid skeleton were seemed to be responsible for the stronger activity.

• Archives of Pharmacal Research
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• 제24권4호
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• pp.292-296
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• 2001

Three prolyl endopeptidase (PEP) inhibitors were isolated from the methanolic extract of green tea leaves. They were identified as (-)-epigallocatechin gallate, (-)-epicatechin gallate, and (+)-gallucatechin gallate with the $IC_{50}$ values of 1.42${\times}$$10^{-4}$mM, $1.02{\times}10^{-2}$mM, and $1.09{\times}10^{-4}$mM, respectively. They were non-competitive with a substrate in Dixon plots and did not show any significant effects against other serine proteases such as elastase, trypsin, and chymotrypsin, suggesting that they were relatively specific inhibitors against PER The isolated compounds are expected to be useful for preventing and curing of Alzheimer's disease.

• 한국약용작물학회지
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• 제12권1호
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• pp.1-9
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• 2004

200종의 식물추출물을 대상으로 PEP 저해활성을 측정한 결과, 81종의 식물추출물은 $10{\sim}30%$ 범위의 저해율을, 28종의 식물추출물은 10%이하의 저해율을 나타내어 총 200종의 식물추출물 중 약 55% 정도의 식물추출물이 30%이하의 낮은 PEP 저해활성을 나타내었다. 반면에, Prunus mume (매화나무) 잎 (95.3%), 노루발과 (Pyrolaceae)의 Pyrola japonica (노루발) 잎과 줄기 (93.2%), 물레나물과 (Hypericaseae)의 Hypericum ascyron (물레나물) 지상부 (90.2%), 범의귀과(Saxifragaceae)의 Astilbe chinensis var. typica (노루오줌) 지상부 (90.1%), 보리수나무과 (Elaeagnaceae)의 Elaeagnus umbellata (보리수나무) 잎과 줄기 (90.1%)등 5종의 추출물들이 5 ppm에서 PEP에 대하여 90% 이상의 강한 저해활성을 나타내었다.