• Nutrition Research and Practice
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• 제5권2호
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• pp.93-100
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• 2011

Inhibition of angiotensin I-converting enzyme (ACE) activity is the most common mechanism underlying the lowering of blood pressure. In the present study, five organic extracts of a marine brown seaweed Ecklonia cava were prepared by using ethanol, ethyl acetate, chloroform, hexane, and diethyl ether as solvents, which were then tested for their potential ACE inhibitory activities. Ethanol extract showed the strongest ACE inhibitory activity with an $IC_{50}$ value of 0.96 mg/ml. Five kinds of phlorotannins, phloroglucinol, triphlorethol-A, eckol, dieckol, and eckstolonol, were isolated from ethanol extract of E. cava, which exhibited potential ACE inhibition. Dieckol was the most potent ACE inhibitor and was found to be a non-competitive inhibitor against ACE according to Lineweaver-Burk plots. Dieckol had an inducible effect on the production of NO in EAhy926 cells without having cytotoxic effect. The results of this study indicate that E. cava could be a potential source of phlorotalnnins with ACE inhibitory activity for utilization in production of functional foods.

• 약학회지
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• 제45권1호
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• pp.93-100
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• 2001

Drug inetraction between of enalapril-induced angiotensin converting enzym) inhibitory effect and Ginkgo biloba Ext.-induced antioxidant action was evaluated in spontaneously hypertensive rats. Combination treatment of enalapril (20 mg/kg/day p.o.) and Ginkgo biloba Ext. (60 mg/kg/day, p.o.) for 6 weeks in drinking water to SHRs resulted the inhibition of ACE activity in lung tissue, angiotensin I-induced pressure response and plasma angiotensin II concentration as similar to enalapril alone treatment. But these effects were sustained after 1 week withdrawal of enalapril and Ginkgo biloba Ext. co-administeration. Also, coadministered group did not increase the concentration of bradykinin in lung tissue, which were different from enalapril alone treated group. Co-administration of enalapril and Ginkgo biloba Ext. inhibited the hemolysis induced by UV B type, even Ginkgo biloba Ext. alone treated group did not. These results suggested that Ginkgo biloba Ext. sustained ACE inhibitory effect and reduced the inhibitory effect of bradykinin inactivation induced by enalapril, meanwhile, enalapril increased the antioxidant effect of Ginkgo biloba Ext.

• 한국축산식품학회지
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• 제43권1호
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• pp.184-194
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• 2023

Recently, interest in food-derived bioactive peptides as promising ingredients for the prevention and improvement of hypertension is increasing. The purpose of this study was to determine the structure and antihypertensive effect of an antioxidant peptide purified from velvet antler in a previous study and evaluate its potential as a various bioactive peptide. Molecular weight (MW) and amino acid sequences of the purified peptide were determined by quadrupole time-of-flight electrospray ionization mass spectroscopy. The angiotensin I-converting enzyme (ACE) inhibition activity of the purified peptide was assessed by enzyme reaction methods and in silico molecular docking analysis to determine the interaction between the purified peptide and ACE. Also, antihypertensive effect of the purified peptide in spontaneously hypertensive rats (SHRs) was investigated. The purified antioxidant peptide was identified to be a pentapeptide Asp-Asn-Arg-Tyr-Tyr with a MW of 730.31 Da. This pentapeptide showed potent inhibition activity against ACE (IC₅₀ value, 3.72 μM). Molecular docking studies revealed a good and stable binding affinity between purified peptide and ACE and indicated that the purified peptide could interact with HOH2570, ARG522, ARG124, GLU143, HIS387, TRP357, and GLU403 residues of ACE. Furthermore, oral administration of the pentapeptide significantly reduced blood pressure in SHRs. The pentapeptide derived from enzymatic hydrolysate of velvet antler is an excellent ACE inhibitor. It might be effectively applied as an animal-based functional food ingredient.

• Applied Biological Chemistry
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• 제51권2호
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• pp.93-101
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• 2008

본 연구는 내산성과 담즙산 내성이 뛰어나고 건강증진 효과가 우사한 L. acidophilus를 신생아의 분변에서 분리 및 선발하고 이들에 의한 장내 유해미생물 생육억제, 혈중 cholesterol 저하 및 과산화수소에 대한 저항성과 탈지유 발효를 통한 풍미성분 형성, ACE 저해활성, 철분가용성 증진 등에 관한 기초 지식을 확보하여 다양한 생리활성 기능을 가진 유산균을 개발하고자 실시하였다. 실험 결과 신생아(생후 2주 이내)에서 분리된 5종의 L. acidophilus 중 특히 L. acidophilus SD 105는 Listeria sp.에 대한 항균활성, 복합담증산염 분해활성 및 항산화효과가 다른 시험 균주에 비해 모두 높게 나타나 그 이용성이 매우 다양할 것으로 생각된다. 또한 L. acidophilus SD 102는 ACE활성 억제효과가 18%로 시험균주 중에 가장 높았으며 L. acidophilus SD 103은 유단백질 유래 철분가용화 펩타이트 생성능이 높아 철분흡수율 증가와 연관된 probiotic 유산균으로서의 활용가능성이 있는 것으로 사료된다.

• 한국식품과학회지
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• 제29권6호
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• pp.1316-1318
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• 1997

산 casein으로부터 FPLC를 이용하여 gel permeation column으로 ${\kappa}-Casein$을 분획한 다음, 이를 chymosin, pepsin, trypsin 으로 각각 처리하여 3% TCA에서 soluble한 부분을 증류수로 투석(MW cut-off 1kDa)시킨 후 ACE저해 효과를 측정한 결과, trypsin으로 분해 시킨 경우 ACE 저해율이 94.7%로 가장 높게 나타났으며, chymosin 가수분해물은 가장 낮았다. GMP를 투석막의 종류에 따라 투석 시킨 후 $IC_{50}$을 측정한 결과, MW cut-off 의 크기가 증가할수록 ACE저해효과는 감소하는 것으로 나타났으며, MW cut-off 2 kDa의 경우가 가장 높은 저해율을 보였고 MW cut-off 5kDa에서는 저해율이 가장 낮았다.

• 한국식품과학회지
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• 제33권1호
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• pp.84-88
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• 2001

우리 나라 전통발효식품인 된장으로부터 angiotensin 전환효소(angiotensin converting enzyme, ACE) 저해활성이 우수한 균주 SYG3를 분리하여 형태학적, 배양학적, 생리학적인 특성을 조사한 결과 B. pumilus 또는 그 유연균으로 동정되었다. 분리 균주의 ACE 저해물질 생산조건을 알아보기 위해 각종 배양조건에 따른 저해활성을 조사한 결과, 탄소원으로서는 glucose, 질소원으로서는 soybean powder에서 가장 높은 저해활성을 나타내었으며, skim milk와 casein에서도 비교적 높은 저해활성을 나타내었다. Soybean powder 농도에 따른 저해활성은 5%(w/v) 첨가시 가장 높은 저해활성을 나타내었으며. 그 이상의 농도에서는 저해활성의 변화가 거의 없었다. NaCl 농도는 3%(w/v) 첨가시 저해활성이 가장 높은 것으로 나타났으며 배양온도는 $32^{\circ}C$, 초기 pH 7.0에서 가장 높은 저해활성을 나타내었다. 최적배지조건에서의 배양시간에 따른 ACE 저해활성은 배양 36시간에 약 98%로서 최고에 도달하였다.

• Journal of Microbiology and Biotechnology
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• 제16권9호
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• pp.1399-1404
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• 2006

The roots of Aralia continentalis (AC) have been used traditionally in Korean as a folk medicine for anti-inflammation and as an anti-rheumatic. In this study, we report that the ethyl acetate-soluble traction (ACE) of the methanolic extract of AC root inhibited the cell growth of various human cancer cell lines and induced apoptosis of HL-60, human promyelocytic leukemia cells. Its $IC_{50}$ values on growth inhibition were estimated to be $56.3{\mu}g/ml$ on HL-60, $87.2{\mu}g/ml$ on HepG2, $93.2{\mu}g/ml$ on HeLa, $135.5{\mu}g/ml$ on DU-145, and $135.8{\mu}g/ml$ on HT-29 cells. Interestingly, ACE showed no antiproliferative effect on normal lymphocyte cells used as control. Furthermore, nuclear DAPI staining revealed the typical nuclear features of apoptosis in the HL-60 cells exposed to $80{\mu}g/ml$ ACE, and a flow cytometric analysis of the HL-60 cells using propidium iodide showed that the apoptotic cell population increased gradually from 5% at 0 h to 16% at 12 h and 20% at 24 h after treated with $50{\mu}g/ml$ of ACE. TUNEL assay also revealed the apoptotic induction of the HL-60 cells treated with ACE. To obtain further information on the ACE-induced apoptosis, the expression level of certain apoptosis-associated proteins was examined using a Western blot analysis. Treatment of the HL-60 cells with ACE resulted in the activation of caspase-3, and subsequent proteolytic cleavage of poly(ADP-ribose) polymerase (PARP). The above results confirmed that the apoptosis in the HL-60 cells was induced by ACE, and that caspase-3-mediated PARP cleavage was involved in the process.

• 한국식품과학회지
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• 제29권6호
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• pp.1269-1274
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• 1997

국내에서 재배된 Aloe vera에서 생리활성 물질인 acetylmannan을 분리 하고 그 제반의 특성을 규명하고 ACE저해효과 및 동력학적분석을 행한 결과 다음과 같은 결론을 얻었다. 알로에 베라 3.5 Kg으로 부터 에탄올에 불용성 다당체를 수득, 백색의 분말형태인 0.9 g의 acetylmannan을 얻었다. 분리한 acetylmannan은 탄수화물 67%를 함유하고 있으며 만노오즈는 60% 소량의 글루코오즈와 갈락토오즈로 이루어져 있고 아세틸기는 23%를 함유하고 있으며 acetyl group은 IR 스펙트럼에서 $1746\;cm^{-1}$, $1244\;cm^{-1}$ peak으로서 확인하였다. 과요오드 산화법에서 과요오드 음이온 소비량이 포름산 생성량에 비해 많고, 1, 4 글리코사이드 결합으로 이루어져 있음을 확인하였다. 또한 ACE에 대한 $IC_{-50}$ 값은 0.58 mM 이였으며, competitive 저해형식을 나타내었고. Ki 값은 0.068 mM 이였다.

• Tuberculosis and Respiratory Diseases
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• 제69권6호
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• pp.418-425
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• 2010

Background: Little is known about the long-term effects of angiotensin-converting enzyme (ACE) treatment on post-tuberculosis emphysema. This study evaluated the effects of ACE inhibition on cardiac function and gas exchange in patients with post-tuberculosis emphysema. Methods: At baseline and at 6 months after initiation of ACE inhibition therapy, patients underwent pulmonary function testing, arterial blood gas analysis, and echocardiography, both at rest and post exercise. Cardiac output (CO) and right ventricular ejection fraction (RVEF) were measured at those time points as well. Results: After ACE inhibition; resting and post-exercise RVEF ($Mean{\pm}SEM,\;61.5{\pm}1.0,\;67.6{\pm}1.2%$, respectively) were higher than at baseline ($56.9{\pm}1.2,\;53.5{\pm}1.7%$). Resting and post-exercise CO ($6.37{\pm}0.24,\;8.27{\pm}0.34L/min$) were higher than at baseline ($5.42{\pm}0.22,\;6.72{\pm}0.24L/min$). Resting and post-exercise $PaO_2$ ($83.8{\pm}1.6,\;74.0{\pm}1.2mmHg$, respectively) were also higher than at baseline ($74.2{\pm}1.9,\;66.6{\pm}1.6mmHg$). Post-exercise $PaCO_2$($46.3{\pm}1.1mmHg$) was higher than at baseline ($44.9{\pm}1.1;\; Resting\;42.8{\pm}0.8\;vs.\;42.4{\pm}0.9mmHg$). Resting and post-exercise A-a $O_2$ gradient ($12.4{\pm}1.4,\;17.8{\pm}1.5 mmHg$) were lower than at baseline ($22.5{\pm}1.5,\;26.9{\pm}1.6mmHg$). Conclusion: In post-tuberculosis emphysema, RVEF and CO were augmented with a resultant increase in peripheral oxygen delivery after ACE inhibition. These findings suggest that an ACE inhibitor may have the potential to alleviate co-morbid cardiac conditions and benefit the patients with post-tuberculosis emphysema.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.182-182
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• 1994

Angiotensin converting enzyme (ACE)을 비가역적으로 불활성화시킴으로써 오랫동안 작용할 수 있는 고혈압치료제로서의 ACE억제제를 개발하기 위하여pseudomechanism-based inhibition이라는 새로운 억제기전을 가질 것으로 추정되는 아래 그림과 같은 기본 분자구조를 갖는 epoxide 유도체들을 합성하여 in vitro에서 ACE활성 억제효과를, HPLC법을 이용하여 측정하였다. 그 결과 합성되어진 epoxide 유도체들은, epoxide group대신에 sulfhydryl 또는 carboxyl group으로 치환되어져 있는 기존의 ACE 억제제들보다도 효능이 현저히 저하됨으로써, ACE의 $Zn^{2+}$ binding site와는 배위결합력이 미약하다는 것을 의미하여 준다. 또한 유도체들의 phenylring에 chloride, hydroxyl, nitro group과 같은 polar group 의 도입으로 말미암아 ACE 억제효과가 저하됨으로써 이 부위에서의 hydrophobic interaction이 ACE를 억제하는데 중요하다는 것을 시사해 주며 이외에도 이미 알려진 바와같이 carbonyl carbon과 인접한 carbon atom에 methyl group의 도입이 억제효과에 중요한 역활을 하였다. 따라서 향후에는 ACE의 $Zn^{2+}$ binding site와 강력한 배위결합을 하는 carboxyl group을 도입하고 epoxide의 위치를 변경시키며 또한 hydrophobic interaction하는 부위의 구조를 변화시켜 보다 효능이 우수한 새로운 기전의 ACE억제제를 개발해 나가고자 한다.