Displaying publications 21 - 40 of 60 in total

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  1. ACE2 activation by xanthenone prevents leptin-induced increases in blood pressure and proteinuria during pregnancy in Sprague-Dawley rats
    Ibrahim HS, Froemming GR, Omar E, Singh HJ
    Reprod Toxicol, 2014 Nov;49:155-61.
    PMID: 25205467 DOI: 10.1016/j.reprotox.2014.08.006
    This study investigates the effect of ACE2 activation on leptin-induced changes in systolic blood pressure (SBP), proteinuria, endothelial activation and ACE2 expression during pregnancy in Sprague-Dawley rats. Pregnant rats were given subcutaneous injection of either saline, or leptin, or leptin plus xanthenone (ACE2 activator), or xanthenone (XTN) alone. SBP, serum ACE, ACE2, endothelin-1, E-selectin and ICAM-1 levels were estimated; also their gene expressions were determined in the kidney and aorta respectively. Compared to control, SBP was higher in the leptin-only treated group (P<0.001) and lower in rats treated with xanthenone alone (P<0.01). Proteinuria, markers of endothelial activation were significantly higher than controls in leptin-only treated rats (P<0.05). ACE2 activity and expression were lower in leptin-only treated rats when compared to controls (P<0.05). It seems, leptin administration during pregnancy significantly increases SBP, proteinuria, endothelial activation, but decreases ACE2 level and expression. These effects are prevented by concurrent administration of xanthenone.
    Matched MeSH terms: Peptidyl-Dipeptidase A/drug effects*; Peptidyl-Dipeptidase A/metabolism
  2. Fulltext Natural Flavonoids as Potential Angiotensin-Converting Enzyme 2 Inhibitors for Anti-SARS-CoV-2
    Muchtaridi M, Fauzi M, Khairul Ikram NK, Mohd Gazzali A, Wahab HA
    Molecules, 2020 Sep 01;25(17).
    PMID: 32882868 DOI: 10.3390/molecules25173980
    Over the years, coronaviruses (CoV) have posed a severe public health threat, causing an increase in mortality and morbidity rates throughout the world. The recent outbreak of a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the current Coronavirus Disease 2019 (COVID-19) pandemic that affected more than 215 countries with over 23 million cases and 800,000 deaths as of today. The situation is critical, especially with the absence of specific medicines or vaccines; hence, efforts toward the development of anti-COVID-19 medicines are being intensively undertaken. One of the potential therapeutic targets of anti-COVID-19 drugs is the angiotensin-converting enzyme 2 (ACE2). ACE2 was identified as a key functional receptor for CoV associated with COVID-19. ACE2, which is located on the surface of the host cells, binds effectively to the spike protein of CoV, thus enabling the virus to infect the epithelial cells of the host. Previous studies showed that certain flavonoids exhibit angiotensin-converting enzyme inhibition activity, which plays a crucial role in the regulation of arterial blood pressure. Thus, it is being postulated that these flavonoids might also interact with ACE2. This postulation might be of interest because these compounds also show antiviral activity in vitro. This article summarizes the natural flavonoids with potential efficacy against COVID-19 through ACE2 receptor inhibition.
    Matched MeSH terms: Peptidyl-Dipeptidase A/metabolism; Peptidyl-Dipeptidase A/chemistry
  3. Fulltext Human coronaviruses: ophthalmic manifestations
    Abdul-Kadir MA, Lim LT
    BMJ Open Ophthalmol, 2020;5(1):e000630.
    PMID: 33195813 DOI: 10.1136/bmjophth-2020-000630
    The 2019 novel coronavirus which causes severe acute respiratory syndrome (SARS) known as SARS-CoV-2 still remains as a global pandemic since its discovery and continues to spread across the world, given how highly contagious the virus is. We reviewed various articles that explore eye involvement in COVID-19 and other human coronaviruses, its human manifestations in comparison to animal studies and potential mechanism of viral entry into the eye surface. Evidence of animal studies depicted various complications of coronaviruses infection into the eyes, in both anterior and posterior segments of the eye. Conjunctival inflammation remains uncommon in association with COVID-19, with other ophthalmic findings. The risk of transmission via the ocular surface remains likely low, though it is inarguably present based on preliminary finding of viral load in ocular samples and expression of ACE2 on the ocular surface. Testing the tears sample for diagnosing SARS-CoV-2 was unreliable due to limitations of the testing kits and conflicting evidence of the viral titre in the ocular samples. Further larger, more precise and specific studies are required to allow us to better understand the pattern of virulence underlying the associations of SARS-CoV-2 in the eye despite its rare occurrence. This review article aims to enhance better awareness among clinicians regarding ocular manifestations associated with COVID-19 and necessary precautions should be implemented to minimise the risk of person-to-person especially in the nosocomial setting.
    Matched MeSH terms: Peptidyl-Dipeptidase A
  4. Molecular docking of compounds from Clinacanthus nutans extract detected by GC-MS analysis with the SARS-CoV-2 main protease and ACE2 protein
    Ismail NZ, Adebayo IA, Mohamad Zain NN, Arsad H
    Nat Prod Res, 2021 May 05.
    PMID: 33949277 DOI: 10.1080/14786419.2021.1919104
    Clinacanthus nutans has been reported to have many medicinal properties and it is traditionally used in treating viral lesions. This study aims to determine the molecular docking of C. nutans compounds detected by Gas Chromatography-Mass Spectrometry (GC-MS) with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 main protease) protein and its host receptor angiotensin-converting enzyme 2 (ACE2) protein using the AutoDock 4.2 tool. The drug-likeness and molecular docking analyses showed that fourteen compounds of C. nutans satisfied the Lipinski's rule of five and they exhibited good inhibitory effects against the SARS-Cov-2 main protease and ACE2 proteins. In addition, the glyceryl 2-linolenate compound was found to have the most potent binding affinities with both proteins. The results provide useful insights into the molecular inhibitory interactions of C. nutans compounds detected by GC-MS analysis with the targeted SARS-CoV-2 main protease and ACE2 protein.
    Matched MeSH terms: Peptidyl-Dipeptidase A
  5. Fulltext A brief review on ACE I/D gene polymorphism and blood pressure response to exercise training
    Hazwani Ahmad Yusof, Abdul Rashid Aziz, Nor Farah Mohamad Fauzi, Ahmad Munir Che Muhamed
    Malaysian Journal of Medicine and Health Sciences, 2018;14(201):179-189.
    MyJurnal
    Exercise has been suggested as the best and the most affordable way for managing blood pressure. The insertion/ deletion of angiotensin I-converting enzyme (ACE) I/D gene polymorphism had been reported to be linked with sev- eral diseases such as hypertension and diabetic nephropathy. Several studies showed that blood pressure response to exercise training for health management also vary among individuals with different genotypes of ACE I/D gene poly- morphism. A study of 9 months of endurance exercise training at 75 to 85 % of VO2max showed that the decrease of resting blood pressure in I allele carriers wass greater than D allele carriers. In contrast, other study discovered that adult women with D allele had greater reduction in resting blood pressure than those with I allele, following a 12-week combined aerobic and resistance exercise training. Despite the inconsistencies of some findings, it has remained unknown if the ACE I/D gene polymorphism would also influence blood pressure response to isometric handgrip training that had been found to be superior to the dynamic resistance exercise training in controlling and preventing high blood pressure. Thus, this article was to review the literature on ACE I/D gene polymorphism and blood pressure response to exercise training that could serve as the basis for future research to identify individuals who will lower resting blood pressure the most with exercise training program for health management.
    Matched MeSH terms: Peptidyl-Dipeptidase A
  6. Fulltext Identification of angiotensin I converting enzyme inhibitory and radical scavenging bioactive peptides from sea cucumber (Stichopus vastus) collagen hydrolysates through optimization
    Abedin, M.Z., Karim, A.A., Gan, C.Y., Ghazali, F.C., Barzideh, Z., Zzaman, W., et al.
    International Food Research Journal, 2015;22(3):1074-1082.
    MyJurnal
    The sea cucumber (Stichopus vastus) is an underutilized species, as most of its parts, including the integument (high collagen content) are thrown away during processing. The aim of this study was to investigate the effects of different hydrolysis conditions (substrate to enzyme ratio (S/E), reaction temperature, and hydrolysis time) on the angiotensin I converting enzyme (ACE) inhibitory and radical scavenging (RSc) activities of the hydrolysates produced from trypsin hydrolysis of S. vastus collagen. Optimal conditions predicted by Box-Behnken Design modelling for producing ACE inhibitory and RSc hydrolysates were found to be S/E ratio (15), reaction temperature (55°C), and hydrolysis time (1 h). Under optimal conditions, ACE inhibitory and RSc activities were estimated to be as high as 67.8% and 77.9%, respectively. Besides, some novel bioactive peptides were identified through mass spectrometry analysis. These results indicate that S. vastus hydrolysates might be used as a functional ingredient in food and nutraceutical products.
    Matched MeSH terms: Peptidyl-Dipeptidase A
  7. Fulltext Enzyme Hydrolysates from Stichopus horrens as a New Source for Angiotensin-Converting Enzyme Inhibitory Peptides
    Forghani B, Ebrahimpour A, Bakar J, Abdul Hamid A, Hassan Z, Saari N
    Evid Based Complement Alternat Med, 2012;2012:236384.
    PMID: 22927875 DOI: 10.1155/2012/236384
    Stichopus horrens flesh was explored as a potential source for generating peptides with angiotensin-converting enzyme (ACE) inhibitory capacity using 6 proteases, namely alcalase, flavourzyme, trypsin, papain, bromelain, and protamex. Degree of hydrolysis (DH) and peptide profiling (SDS-PAGE) of Stichopus horrens hydrolysates (SHHs) was also assessed. Alcalase hydrolysate showed the highest DH value (39.8%) followed by flavourzyme hydrolysate (32.7%). Overall, alcalase hydrolysate exhibited the highest ACE inhibitory activity (IC(50) value of 0.41 mg/mL) followed by flavourzyme hydrolysate (IC(50) value of 2.24 mg/mL), trypsin hydrolysate (IC(50) value of 2.28 mg/mL), papain hydrolysate (IC(50) value of 2.48 mg/mL), bromelain hydrolysate (IC(50) value of 4.21 mg/mL), and protamex hydrolysate (IC(50) value of 6.38 mg/mL). The SDS-PAGE results showed that alcalase hydrolysate represented a unique pattern compared to others, which yielded potent ACE inhibitory peptides with molecular weight distribution lower than 20 kDa. The evaluation of the relationship between DH and IC(50) values of alcalase and flavourzyme hydrolysates revealed that the trend between those parameters was related to the type of the protease used. We concluded that the tested SHHs would be used as a potential source of functional ACE inhibitory peptides for physiological benefits.
    Matched MeSH terms: Peptidyl-Dipeptidase A
  8. Fulltext Gallium scan in diagnosing ocular sarcoidosis
    Ismail S, Embong Z, Hitam WH
    Malays J Med Sci, 2005 Jan;12(1):64-7.
    PMID: 22605949
    A 40-year-old man presented with floaters and painless progressive blurring of vision in the right eye for one month duration. Visual acuity in the right eye was 6/24. There was mild anterior chamber reaction and vitritis. The optic disc was swollen and elevated with presence of granulomatous lesion in the optic disc head. Blood investigations were unremarkable. Serum angiotensin converting enzyme (ACE) was normal and conjunctival biopsy showed presence of inflammatory cells. B-Scan ultrasound revealed an echo-dense lesion in the optic nerve head. There was increased uptake of the right lacrimal gland and presence of 'Panda sign' with Gallium scan. A diagnosis of right ocular sarcoidosis was made base on the clinical features and Gallium scan.
    Matched MeSH terms: Peptidyl-Dipeptidase A
  9. Fulltext Renin-Angiotensin System Gene Variants and Type 2 Diabetes Mellitus: Influence of Angiotensinogen
    Joyce-Tan SM, Zain SM, Abdul Sattar MZ, Abdullah NA
    J Diabetes Res, 2016;2016:2161376.
    PMID: 26682227 DOI: 10.1155/2016/2161376
    Genome-wide association studies (GWAS) have been successfully used to call for variants associated with diseases including type 2 diabetes mellitus (T2DM). However, some variants are not included in the GWAS to avoid penalty in multiple hypothetic testing. Thus, candidate gene approach is still useful even at GWAS era. This study attempted to assess whether genetic variations in the renin-angiotensin system (RAS) and their gene interactions are associated with T2DM risk. We genotyped 290 T2DM patients and 267 controls using three genes of the RAS, namely, angiotensin converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II type 1 receptor (AGTR1). There were significant differences in allele frequencies between cases and controls for AGT variants (P = 0.05) but not for ACE and AGTR1. Haplotype TCG of the AGT was associated with increased risk of T2DM (OR 1.92, 95% CI 1.15-3.20, permuted P = 0.012); however, no evidence of significant gene-gene interactions was seen. Nonetheless, our analysis revealed that the associations of the AGT variants with T2DM were independently associated. Thus, this study suggests that genetic variants of the RAS can modestly influence the T2DM risk.
    Matched MeSH terms: Peptidyl-Dipeptidase A/genetics
  10. Fulltext Angiotensin-I Converting Enzyme (ACE) Inhibitory and Anti-Oxidant Activities of Sea Cucumber (Actinopyga lecanora) Hydrolysates
    Ghanbari R, Zarei M, Ebrahimpour A, Abdul-Hamid A, Ismail A, Saari N
    Int J Mol Sci, 2015 Dec 04;16(12):28870-85.
    PMID: 26690117 DOI: 10.3390/ijms161226140
    In recent years, food protein-derived hydrolysates have received considerable attention because of their numerous health benefits. Amongst the hydrolysates, those with anti-hypertensive and anti-oxidative activities are receiving special attention as both activities can play significant roles in preventing cardiovascular diseases. The present study investigated the angiotensin-I converting enzyme (ACE) inhibitory and anti-oxidative activities of Actinopyga lecanora (A. lecanora) hydrolysates, which had been prepared by alcalase, papain, bromelain, flavourzyme, pepsin, and trypsin under their optimum conditions. The alcalase hydrolysate showed the highest ACE inhibitory activity (69.8%) after 8 h of hydrolysis while the highest anti-oxidative activities measured by 2,2-diphenyl 1-1-picrylhydrazyl radical scavenging (DPPH) (56.00%) and ferrous ion-chelating (FIC) (59.00%) methods were exhibited after 24 h and 8 h of hydrolysis, respectively. The ACE-inhibitory and anti-oxidative activities displayed dose-dependent trends, and increased with increasing protein hydrolysate concentrations. Moreover, strong positive correlations between angiotensin-I converting enzyme (ACE) inhibitory and anti-oxidative activities were also observed. This study indicates that A. lecanora hydrolysate can be exploited as a source of functional food owing to its anti-oxidant as well as anti-hypertension functions.
    Matched MeSH terms: Peptidyl-Dipeptidase A/metabolism
  11. Signaling pathway genes for blood pressure, folate and cholesterol levels among hypertensives: an epistasis analysis
    Wei LK, Menon S, Griffiths LR, Gan SH
    J Hum Hypertens, 2015 Feb;29(2):99-104.
    PMID: 25055800 DOI: 10.1038/jhh.2014.53
    Irregular atrial pressure, defective folate and cholesterol metabolism contribute to the pathogenesis of hypertension. However, little is known about the combined roles of the methylenetetrahydrofolate reductase (MTHFR), apolipoprotein-E (ApoE) and angiotensin-converting enzyme (ACE) genes, which are involved in metabolism and homeostasis. The objective of this study is to investigate the association of the MTHFR 677 C>T and 1298A>C, ACE insertion-deletion (I/D) and ApoE genetic polymorphisms with hypertension and to further explore the epistasis interactions that are involved in these mechanisms. A total of 594 subjects, including 348 normotensive and 246 hypertensive ischemic stroke subjects were recruited. The MTHFR 677 C>T and 1298A>C, ACE I/D and ApoEpolymorphisms were genotyped and the epistasis interaction were analyzed. The MTHFR 677 C>T and ApoE polymorphisms demonstrated significant associations with susceptibility to hypertension in multiple logistic regression models, multifactor dimensionality reduction and a classification and regression tree. In addition, the logistic regression model demonstrated that significant interactions between the ApoE E3E3, E2E4, E2E2 and MTHFR 677 C>T polymorphisms existed. In conclusion, the results of this epistasis study indicated significant association between the ApoE and MTHFR polymorphisms and hypertension.
    Matched MeSH terms: Peptidyl-Dipeptidase A/genetics*
  12. Fulltext Novel angiotensin I-converting enzyme inhibitory peptides derived from an edible mushroom, Pleurotus cystidiosus O.K. Miller identified by LC-MS/MS
    Lau CC, Abdullah N, Shuib AS
    BMC Complement Altern Med, 2013 Nov 11;13:313.
    PMID: 24215325 DOI: 10.1186/1472-6882-13-313
    BACKGROUND: Angiotensin I-converting enzyme (ACE) inhibitors have been reported to reduce mortality in patients with hypertension. Compared to chemosynthetic drugs, ACE inhibitors derived from natural sources such as food proteins are believed to be safer for consumption and to have fewer adverse effects. Some edible mushrooms have been reported to significantly reduce blood pressure after oral administration. In addition, mushrooms are known to be rich in protein content. This makes them a potential source of ACE inhibitory peptides. Hence, the objective of the current study was to isolate and characterise ACE inhibitory peptides from an edible mushroom, Pleurotus cystidiosus.

    METHODS: ACE inhibitory proteins were isolated from P. cystidiosus based on the bioassay guided purification steps, i.e. ammonium sulphate precipitation, reverse phase high performance liquid chromatography and size exclusion chromatography. Active fraction was then analysed by LC-MS/MS and potential ACE inhibitory peptides identified were chemically synthesized. Effect of in vitro gastrointestinal digestions on the ACE inhibitory activity of the peptides and their inhibition patterns were evaluated.

    RESULTS: Two potential ACE inhibitory peptides, AHEPVK and GPSMR were identified from P. cystidiosus with molecular masses of 679.53 and 546.36 Da, respectively. Both peptides exhibited potentially high ACE inhibitory activity with IC50 values of 62.8 and 277.5 μM, respectively. SEC chromatograms and BIOPEP analysis of these peptides revealed that the peptide sequence of the hexapeptide, AHEPVK, was stable throughout gastrointestinal digestion. The pentapeptide, GPSMR, was hydrolysed after digestion and it was predicted to release a dipeptide ACE inhibitor, GP, from its precursor. The Lineweaver-Burk plot of AHEPVK showed that this potent and stable ACE inhibitor has a competitive inhibitory effect against ACE.

    CONCLUSION: The present study indicated that the peptides from P. cystidiosus could be potential ACE inhibitors. Although these peptides had lower ACE inhibitory activity compared to commercial antihypertensive drugs, they are derived from mushroom which could be easily obtained and should have no side effects. Further in vivo studies can be carried out to reveal the clear mechanism of ACE inhibition by these peptides.

    Matched MeSH terms: Peptidyl-Dipeptidase A/chemistry
  13. Extraction of antioxidative and antihypertensive bioactive peptides from Parkia speciosa seeds
    Siow HL, Gan CY
    Food Chem, 2013 Dec 15;141(4):3435-42.
    PMID: 23993504 DOI: 10.1016/j.foodchem.2013.06.030
    Antioxidative and antihypertensive bioactive peptides were successfully derived from Parkia speciosa seed using alcalase. The effects of temperature (25 and 50 °C), substrate-to-enzyme ratio (S/E ratio, 20 and 50), and incubation time (0.5, 1, 2 and 5h) were evaluated based on 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and angiotensin-converting enzyme (ACE) assays. Bioactive peptide extracted at a hydrolysis condition of: temperature=50 °C, S/E ratio=50 and incubation time=2h, exhibited the highest DPPH radical scavenging activity (2.9 mg GAE/g), reducing power (11.7 mM) and %ACE-inhibitory activity (80.2%). The sample was subsequently subjected to fractionation and the peptide fraction of <10 kDa showed the strongest bioactivities. A total of 29 peptide sequences from peptide fraction of <10 kDa were identified as the most potent contributors to the bioactivities. These novel bioactive peptides were suggested to be beneficial to nutraceutical and food industries.
    Matched MeSH terms: Peptidyl-Dipeptidase A/analysis
  14. Does SARS-CoV-2 infection cause sperm DNA fragmentation? Possible link with oxidative stress
    Sengupta P, Dutta S
    Eur J Contracept Reprod Health Care, 2020 Oct;25(5):405-406.
    PMID: 32643968 DOI: 10.1080/13625187.2020.1787376
    Matched MeSH terms: Peptidyl-Dipeptidase A/metabolism*
  15. Fulltext The toxicity of angiotensin converting enzyme inhibitors to larvae of the disease vectors Aedes aegypti and Anopheles gambiae
    Abu Hasan Z', Williams H, Ismail NM, Othman H, Cozier GE, Acharya KR, et al.
    Sci Rep, 2017 03 27;7:45409.
    PMID: 28345667 DOI: 10.1038/srep45409
    The control of mosquitoes is threatened by the appearance of insecticide resistance and therefore new control chemicals are urgently required. Here we show that inhibitors of mosquito peptidyl dipeptidase, a peptidase related to mammalian angiotensin-converting enzyme (ACE), are insecticidal to larvae of the mosquitoes, Aedes aegypti and Anopheles gambiae. ACE inhibitors (captopril, fosinopril and fosinoprilat) and two peptides (trypsin-modulating oostatic factor/TMOF and a bradykinin-potentiating peptide, BPP-12b) were all inhibitors of the larval ACE activity of both mosquitoes. Two inhibitors, captopril and fosinopril (a pro-drug ester of fosinoprilat), were tested for larvicidal activity. Within 24 h captopril had killed >90% of the early instars of both species with 3rd instars showing greater resistance. Mortality was also high within 24 h of exposure of 1st, 2nd and 3rd instars of An. gambiae to fosinopril. Fosinopril was also toxic to Ae. aegypti larvae, although the 1st instars appeared to be less susceptible to this pro-drug even after 72 h exposure. Homology models of the larval An. gambiae ACE proteins (AnoACE2 and AnoACE3) reveal structural differences compared to human ACE, suggesting that structure-based drug design offers a fruitful approach to the development of selective inhibitors of mosquito ACE enzymes as novel larvicides.
    Matched MeSH terms: Peptidyl-Dipeptidase A/metabolism
  16. Renin-Angiotensin-Aldosterone System Gene Polymorphisms and Type 2 Diabetic Nephropathy in Asian Populations: An Updated Meta-analysis
    Ahmad N, Jamal R, Shah SA, Gafor AHA, Murad NAA
    Curr Diabetes Rev, 2019;15(4):263-276.
    PMID: 29984662 DOI: 10.2174/1573399814666180709100411
    BACKGROUND: The association of polymorphisms in the renin-angiotensin-aldosterone system candidate genes, namely Angiotensin-Converting Enzyme (ACE) Insertion/Deletion (I/D), Angiotensinogen (AGT) M235T and Angiotensin II Receptor Type 1 (AGTR1) A1166C with Diabetic Nephropathy (DN) has been studied for decades.

    OBJECTIVE: This meta-analysis aimed to assess the updated pooled effects of these polymorphisms with DN among Asian populations with type 2 diabetes mellitus.

    METHODS: The PubMed electronic database was searched without duration filter until August 2017 and the reference list of eligible studies was screened. The association of each polymorphism with DN was examined using odds ratio and its 95% confidence interval based on dominant, recessive and allele models. Subgroup analyses were conducted based on region, DN definition and DM duration.

    RESULTS: In the main analysis, the ACE I/D (all models) and AGTR1 A1166C (dominant model) showed a significant association with DN. The main analysis of the AGT M235T polymorphism did not yield significant findings. There were significant subgroup differences and indication of significantly higher odds for DN in terms of DM duration (≥10 years) for ACE I/D (all models), AGT M235T (recessive and allele models) and AGTR1 A1166C (recessive model). Significant subgroup differences were also observed for DN definition (advanced DN group) and region (South Asia) for AGTR1 A1166C (recessive model).

    CONCLUSION: In the Asian populations, ACE I/D and AGTR1 A1166C may contribute to DN susceptibility in patients with T2DM by different genetic models. However, the role of AGT M235T needs to be further evaluated.

    Matched MeSH terms: Peptidyl-Dipeptidase A/genetics
  17. Fulltext Effects of Root Extracts of Eurycoma longifolia Jack on Corpus Cavernosum of Rat
    Tee BH, Hoe SZ, Cheah SH, Lam SK
    Med Princ Pract, 2017;26(3):258-265.
    PMID: 28226311 DOI: 10.1159/000464363
    OBJECTIVE: This study was conducted to investigate the mechanisms of action of Eurycoma longifolia in rat corpus cavernosum.

    MATERIALS AND METHODS: Tincture of the roots was concentrated to dryness by evaporating the ethanol in vacuo. This ethanolic extract was partitioned into 5 fractions sequentially with hexane, dichloromethane (DCM), ethyl acetate, butanol, and water. The corpus cavernosum relaxant activity of each fraction was investigated. The DCM fraction which showed the highest potency in relaxing phenylephrine-precontracted corpora cavernosa was purified by column chromatography. The effects of the most potent DCM subfraction in relaxing phenylephrine-precontracted corpora cavernosa, DCM-I, on angiotensin I- or angiotensin II-induced contractions in corpora cavernosa were investigated. The effects of DCM-I pretreatment on the responses of phenylephrine-precontracted corpora cavernosa to angiotensin II or bradykinin were also studied. An in vitro assay was conducted to evaluate the effect of DCM-I on angiotensin-converting enzyme activity.

    RESULTS: Fraction DCM-I decreased the maximal contractions (100%) evoked by angiotensin I and angiotensin II to 30 ± 14% and 26 ± 16% (p < 0.001), respectively. In phenylephrine-precontracted corpora cavernosa, DCM-I pretreatment caused angiotensin II to induce 82 ± 27% relaxation of maximal contraction (p < 0.01) and enhanced (p < 0.001) bradykinin-induced relaxations from 47 ± 8% to 100 ± 5%. In vitro, DCM-I was able to reduce (p < 0.001) the maximal angiotensin-converting enzyme activity to 78 ± 0.24%.

    CONCLUSION: Fraction DCM-I was able to antagonize angiotensin II-induced contraction to cause corpus cavernosum relaxation via inhibition of angiotensin II type 1 receptor and enhance bradykinin-induced relaxation through inhibition of angiotensin-converting enzyme.

    Matched MeSH terms: Peptidyl-Dipeptidase A/drug effects
  18. Fulltext The effects of angiotensin-converting enzyme gene polymorphism on the progression of immunoglobulin A nephropathy in Malaysian patients
    Draman CR, Kong NC, Gafor AH, Rahman AF, Zainuddin S, Mustaffa WM, et al.
    Singapore Med J, 2008 Nov;49(11):924-9.
    PMID: 19037561
    Angiotensin-converting enzyme (ACE) gene polymorphism, especially the deletion/deletion (DD) genotype, is associated with the disease progression of immunoglobulin A (IgA) nephropathy patients in various studies from both Asia Pacific and European populations. However, recent studies within the same populations were unable to reproduce the same results. Hence, we had studied the distribution of the DD genotype, the association between ACE gene polymorphism and the disease progression, and the factors (other than ACE gene polymorphism) which were involved in the disease progression of our local patients.
    Matched MeSH terms: Peptidyl-Dipeptidase A/genetics*
  19. Synthesis and evaluation of chalcone analogues based pyrimidines as angiotensin converting enzyme inhibitors
    Bukhari SN, Butt AM, Amjad MW, Ahmad W, Shah VH, Trivedi AR
    Pak J Biol Sci, 2013 Nov 01;16(21):1368-72.
    PMID: 24511749
    Hypertension is a widespread and frequently progressive ailment that imparts a foremost threat for cardiovascular and renal disorders. Mammoth efforts are needed for the synthesis of innovative antihypertensive agents to combat this lethal disease. Chalcones have shown antihypertensive activity through inhibition of Angiotensin Converting Enzyme (ACE). Hence, a series of chalcone analogues is synthesized and used as precursor for the synthesis of novel series of pyrimidines. Precursor chalcones were prepared by reacting aldehydes and ketones in presence of sodium hydroxide followed by synthesis of corresponding pyrimidines by reaction with urea in presence of potassium hydroxide. Both groups were then evaluated for their effects on ACE. The results depicted that pyrimidines were more active than chalcones with methoxy (C5 and P5) substitution showing best results to inhibit ACE. Given that chalcone analogues and pyrimidines show a potential as the angiotensin converting enzyme inhibitors.
    Matched MeSH terms: Peptidyl-Dipeptidase A/metabolism
  20. Fulltext Comparative study of Mg/Al- and Zn/Al-layered double hydroxide-perindopril erbumine nanocomposites for inhibition of angiotensin-converting enzyme
    Hussein Al Ali SH, Al-Qubaisi M, Hussein MZ, Ismail M, Zainal Z, Hakim MN
    Int J Nanomedicine, 2012;7:4251-62.
    PMID: 22904631 DOI: 10.2147/IJN.S32267
    The intercalation of a drug active, perindopril, into Mg/Al-layered double hydroxide for the formation of a new nanocomposite, PMAE, was accomplished using a simple ion exchange technique. A relatively high loading percentage of perindopril of about 36.5% (w/w) indicates that intercalation of the active took place in the Mg/Al inorganic interlayer. Intercalation was further supported by Fourier transform infrared spectroscopy, and thermal analysis shows markedly enhanced thermal stability of the active. The release of perindopril from the nanocomposite occurred in a controlled manner governed by pseudo-second order kinetics. MTT assay showed no cytotoxicity effects from either Mg/Al-layered double hydroxide or its nanocomposite, PMAE. Mg/Al-layered double hydroxide showed angiotensin-converting enzyme inhibitory activity, with 5.6% inhibition after 90 minutes of incubation. On incubation of angiotensin-converting enzyme with 0.5 μg/mL of the PMAE nanocomposite, inhibition of the enzyme increased from 56.6% to 70.6% at 30 and 90 minutes, respectively. These results are comparable with data reported in the literature for Zn/Al-perindopril.
    Matched MeSH terms: Peptidyl-Dipeptidase A/metabolism; Peptidyl-Dipeptidase A/chemistry
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