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3D-QSAR Studies on Angiotensin-Converting Enzyme (ACE)Inhibitors: a Molecular Design in Hypertensive Agents

  • San Juan, Amor A.;Cho, Seung-Joo
    • Bulletin of the Korean Chemical Society
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    • v.26 no.6
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    • pp.952-958
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    • 2005
  • Angiotensin-converting enzyme (ACE) is known to be primarily responsible for hypertension. Threedimensional quantitative structure-activity relationship (3D-QSAR) models have been constructed using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) for a series of 28 ACE inhibitors. The availability of ACE crystal structure (1UZF) provided the plausible biological orientation of inhibitors to ACE active site (C-domain). Alignment for CoMFA obtained by docking ligands to 1UZF protein using FlexX program showed better statistical model as compared to superposition of corresponding atoms. The statistical parameters indicate reasonable models for both CoMFA ($q^2$ = 0.530, $r^2$ = 0.998) and CoMSIA ($q^2$ = 0.518, $r^2$ = 0.990). The 3D-QSAR analyses provide valuable information for the design of ACE inhibitors with potent activity towards C-domain of ACE. The group substitutions involving the phenyl ring and carbon chain at the propionyl and sulfonyl moieties of captopril are essential for better activity against ACE.

Evaluation of anti-inflammatory effect by regulating NF-κB pathway of Argyreia capitata (Vahl) Choisy extract in LPS-induced RAW 264.7 macrophages (LPS로 유도된 RAW 264.7 대식세포에서 Argyreia capitata (Vahl) Choisy 추출물의 NF-κB pathway 조절을 통한 항염증 효능 평가)

  • Yeum, Ga Hee;So, Bo Ram;Bach, Tran The;Eum, Sang Mi;Jung, Sung Keun
    • Korean Journal of Food Science and Technology
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    • v.52 no.3
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    • pp.249-254
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    • 2020
  • Argyreia capitata (Vahl) Choisy is a species of the genus Argyreia. Although many studies have analyzed the biological activity of A. nervosa, A. speciasa, and A. acuta, the anti-inflammatory effect of A. capitata extract (ACE) remains unclear. In this study, we evaluated the anti-inflammatory effect of ACE using lipopolysaccharide (LPS)-induced inflammatory markers in RAW 264.7 cells. We confirmed that the ACE inhibited the LPS-induced NO (nitric oxide) and iNOS (inducible nitric oxide synthase) expression in RAW 264.7 cells. ACE suppressed not only the LPS-induced phosphorylation of IKK, IκB, and p65 but also IL-1β expression. Collectively, these results suggest that ACE is a novel anti-inflammatory agent that suppresses iNOS expression, NO production, and the NF-κB signaling pathways.

Screening of Extracts from Red Algae in Jeju for Potentials MarineAngiotensin - I Converting Enzyme (ACE) Inhibitory Activity

  • Cha, Seon-Heui;Lee, Ki-Wan;Jeon, You-Jin
    • ALGAE
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    • v.21 no.3
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    • pp.343-348
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    • 2006
  • This study was conducted to screen in vitro angiotensin - I converting enzyme (ACE) inhibitory activities of methanol (MeOH) and aqueous extracts at 20°C and 70°C, respectively, prepared from twenty-six red algae obtained from the coast of Jeju Island in Korea. Among aqueous extracts at 20°C (20AE) from red algae Lomentaria catenata showed the strongest ACE inhibitory activity and Lithophyllum okamurae recorded the second highest activity. From MeOH extract at 20°C (20ME) Ahnfeltiopsis flabelliformis possessed the strongest ACE inhibitory activity. Remarkable activities from MeOH extracts at 70°C (70ME) were observed in Grateloupia filicina, Sinkoraena lancifolia and Grateloupia lanceolata. However, no significant activity was found in aqueous extracts at 70°C (70AE). The IC50 values, which are concentrations required to inhibit 50% activity of ACE, for ACE inhibitory activities of 20AE from Lithophyllum okamurae and L. catenata were 13.78 and 12.21 μg mL–1, respectively. The IC50 values of 20ME from A. flabelliformis and Laurencia okamurae were 13.84 and 106.15 μg mL–1. Those of the 70ME from Bonnemaisonia hamifera, Grateloupia filicina, Sinkoraena lancifolia, G. lanceolata, Gracilaria vermiculophylla and L. okamurae ranged from 25.82 to 124.69 μg mL–1.

A Study on the Biological Activity of Allium cepa Extract in Vivo (양파 추출물의 in vivo 생리활성에 관한 연구)

  • Lee, Jin Young
    • Journal of Life Science
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    • v.30 no.3
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    • pp.267-277
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    • 2020
  • This study was conducted to assess the effect of highly concentrated onion intake on rodents. The experimental animals were divided two groups as follows; water administered group (CON) and Allium cepa administered group (ACE). The ACE group showed a slightly increases in the number of erythrocytes (RBC), hemoglobin (HGB), hematocrit (Hct) levels compared to the control group (p<0.05). Hemoglobin, monocyte, lymphocyte and neutrophil had no significant change (p>0.05) in ACE group and control group. The analysis of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels showed a significant decrease in ACE group compared to the control group (p<0.05). The blood glucose, total protein, HDL-cholesterol were slightly high in ACE group, while triglyceride, total cholesterol levels were lower in ACE group compared to the control group (p<0.05). The levels of cytokines (interluekin-1α (IL-1α), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), interferon-γ (INF-γ), interleukin-18 (IL-18), interleukin-2 (IL-2), granulocyte-macrophage colony-stimulating factor (GM-CSF)) involved in immunity and inflammation in liver tissue and blood have all been confirmed to be within normal range. These findings could be used as basic data to show that highly concentrated dietary onion extract is not toxic to hematological indicators and immune functions.

Effect of Lactic Acid Bacterium on Antioxidative and ACE inhibitory activity in Dolsan Leaf Mustard Kimchi (유산균 농도가 돌산갓김치의 항산화효과 및 ACE 저해활성에 미치는 효과)

  • 최명락;유은정;임현수
    • Journal of Life Science
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    • v.13 no.1
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    • pp.59-66
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    • 2003
  • The bacterial strain was isolated from the 4th day's fermented Dolsan Leaf Mustard Kimchi(DLMK) at $20^{\circ}C$/TEX>. It was used as Kimchi starter, and then its physiological activity was investigated for 50 days at $4^{\circ}C$/TEX> and $10^{\circ}C$/TEX> The physiological activity of DLMK was examined for both antioxidative and Angiotensine Converting Enzyme(ACE) inhibitory activity. In the starter-inoculated DLMK(1 X $10^{10}$ CFU/mL) at 4 and $10^{\circ}C$, the optimal ripening period was more shortend than that of control(without starter) up to about 5.6 and 5 times, respectively. The maximal antioxidative activity in the starter-inoculated DLMK(1 X $10^{10}$ 10 CFU/mL) at 4 and $10^{\circ}C$ were 67% and 75%, respectively. The yield of cell concentration per day($lnX_{max}$/$t_{max}$) and the yield of antioxidative activity per day($P_{max}$/t$t_{max}$) had a linear relationship. Also, the yield of antioxidative activity per day was increased with increasing the concentration of inoculated bacterium. By adding 1 X $10^{10}$ CFU/mL at 4 and $10^{\circ}C$, the ACE inhibitory activity of DLMK was maximal. The rates of inhibiting activities were 52% and 76%, respectively. Consequently, physiological activities were significantly affected by the inoculation concentrations of starter, but bacterium itself was not appeared the physiological activity. We assume that the bacterium metabolizes certain materials in DLMK and released compounds such as glucosinolates or its metabolized forms from DLMK show the antioxidative and ACE inhibitory activity.

The Novel Angiotensin I Converting Enzyme Inhibitory Peptide from Rainbow Trout Muscle Hydrolysate

  • Kim, Sung-Rae;Byun, Hee-Guk
    • Fisheries and Aquatic Sciences
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    • v.15 no.3
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    • pp.183-190
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    • 2012
  • The purpose of this study was the purification and characterization of an angiotensin I converting enzyme (ACE) inhibitory peptide purified from enzymatic hydrolysates of rainbow trout Oncorhynchus mykiss muscle. After removal of lipid, the approximate composition analysis of the rainbow trout revealed 24.4%, 1.7%, and 68.3% for protein, lipid, and moisture, respectively. Among six hydrolysates, the peptic hydrolysate exhibited the highest ACE inhibitory activity. We attempted to purify ACE inhibitory peptides from peptic hydrolysate using high performance liquid chromatography on an ODS column. The $IC_{50}$ value of purified ACE inhibitory peptide was $63.9{\mu}M$. The amino acid sequence of the peptide was identified as Lys-Val-Asn-Gly-Pro-Ala-Met-Ser-Pro-Asn-Ala-Asn, with a molecular weight of 1,220 Da, and the Lineweaver-Burk plots suggested that they act as a competitive inhibitor against ACE. Our study suggested that novel ACE inhibitory peptides purified from rainbow trout muscle protein may be beneficial as anti-hypertension compounds in functional foods.

Blood Pressure in Relation to α-Adducin, Angiotensinogen, ACE Gene Polymorphisms and Sodium Intake in Korean Female Elderly Subjects (한국 여성 노인에서 α -Adducin, Angiotensinogen, ACE 유전자다형성 및 나트륨 섭취수준에 따른 혈압의 비교)

  • Chae, Sun-Ju;Chung, Ja-Yong
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.10
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    • pp.1371-1377
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    • 2006
  • Gene polymorphisms that are associated with sodium homeostasis in the body, such as $\alpha-adducin$ (ADDI, Gly460Trp), angiotensinogen (AGT, Met235Thr), and angiotensin converting enzyme (ACE, Ins/Del) may increase the risk for the development of hypertension. The purpose of this study was to elucidate the relationship between the singular and combined effects of ADD1, AGT, ACE genotypes, and blood pressure in elderly population. Moreover, we examined the interaction of sodium intake and polymorphisms of aforementioned genes and their effects on blood pressure. Among one hundred and nine female subjects, aged 60 and over (mean 75.9 yr), the major alleles for ADD1, AGT, and ACE polymorphisms in the studied population were Gly (66.1%), Thr (64.2%), Ins (83.5%), respectively. Analysis on the combined effects of genetic variation showed that subjects who were both ADD1 Trp/Trp and ACE Del/Del homozygotes had significantly higher systolic blood pressure (p=0.01). Similarly, ACE Del/Del homozygotes who had AGT Met allele had significantly higher diastolic blood pressure (p<0.001). However, in single-gene analyses, no association was found between any specific genotype and blood pressure. In subjects with low sodium intake, ADD1 Trp/Trp homozygotes had significantly higher systolic blood pressure than subjects who had ADD1 Gly allele (138 mmHg vs. 127 mmHg, p=0.03). There was no difference in blood pressure between ADD1 Trp/Trp and ADD1 Gly/Gly or Gly/Trp, in subjects with high sodium intake. In summary, this study shows that interactions between the ADD1, AGT and ACE genes influence systolic and diastolic blood pressure in elderly subjects, and dietary sodium intake can modulate the effects of ADD1 Gly460Trp polymorphisms on systolic blood pres sure.

Angiotensin-I Converting Enzyme Inhibitory Activity of Algae (해조류의 Angiotensin-I 전환효소 저해작용)

  • LEE Heon-Ok;KIM Dong-Soo;DO Jeong-Ryong;KO Young-Su
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.32 no.4
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    • pp.427-431
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    • 1999
  • This study was conducted to investigate the inhibitory activity of water extracts and its enzymatic hydrolysates from algae against angiotensin-I converting enzyme (ACE). The 7 kinds of algae were extracted with water at $50^{\circ}C,\;70^{\circ}C$ and $98^{\circ}C$. ACE inhibitory activities of water extracts were the highest at $70^{\circ}C$, and those of ceylon moss, layer, green layer, sea mustard, seaweed fusiforme sea tangle and sea staghorn were $10.9\%,\;9.3\%,\;8.9\%,\;8.2\%,\;7.5\%,\;7.1\%$ and $7.0\%$, respectively. Layer, green laver sea mustard and ceylon moss of high ACE inhibitory activities among the 7 kinds of water extracts were hydrolyzed by maxazyme and papain during 24hrs. ACE inhibitory activity of enzymatic hydrolysates was higher than that of water extracts, and was the highest in enzymatic hydrolysates of laver among the tested samples. In laver hydrolysates by proteases, the highest ACE inhibitory activity and peptide-nitrogen contents were observed at 8 hours hydrolysis and the hydrolysates by maxazyme showed relatively higher activity than those by papain(31.3 and $27.9\%$, respectively). But peptide-nitrogen contents were greater in papain hydrolysates than in maxazyme.

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AN INTRODUCTION TO 𝜖0-DENSITY AND 𝜖0-DENSE ACE

  • Kang, Buhyeon
    • Journal of the Chungcheong Mathematical Society
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    • v.32 no.1
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    • pp.69-86
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    • 2019
  • In this paper, we introduce a concept of the ${\epsilon}_0$-limits of vector and multiple valued sequences in $R^m$. Using this concept, we study about the concept of the ${\epsilon}_0$-dense subset and of the points of ${\epsilon}_0$-dense ace in the open subset of $R^m$. We also investigate the properties and the characteristics of the ${\epsilon}_0$-dense subsets and of the points of ${\epsilon}_0$-dense ace.

Improving Cellulase Production in Trichoderma koningii Through RNA Interference on ace1 Gene Expression

  • Wang, Shao-Wen;Xing, Miao;Liu, Gang;Yu, Shao-Wen;Wang, Juan;Tian, Sheng-Li
    • Journal of Microbiology and Biotechnology
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    • v.22 no.8
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    • pp.1133-1140
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    • 2012
  • Ribonucleic acid interference (RNAi) inhibits the expression of target genes in a sequence-specific manner, and shows potential for gene knockdown in filamentous fungi, in which the locus-specific gene knockout occurs in low frequency. In this study, the function of the repressor of cellulase expression I (ACEI) was verified in Trichoderma koningii (T. koningii) YC01 through RNAi, and ace1-silenced strains with improved cellulase productivity were obtained. An expression cassette that transcribed the interfering double-stranded RNA (dsRNA) of ace1 was constructed and transformed into T. koningii, and the transformants, in which the expression of ace1 was successfully silenced, were selected. As a result of the ace1 gene silencing, the expression levels of the main cellulase and xylanase genes were elevated, and the enhanced production of total proteins, cellulase, and xylanase was observed in the cultivation. In addition, the down-regulation of ace1 resulted in an increasing expression of xyr1, but no clear variation in the expression of cre1, which suggested that ACEI acted as a repressor of the xyr1 transcription, but was not involved in the regulation of the cre1 expression. The results of this work indicate that ace1 is a valid target gene for enhancing enzyme production in T. koningii, and RNAi is an appropriate tool for improving the properties of industrial fungi.