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Plant Flavonoids as Angiotensin Converting Enzyme Inhibitors in Regulation of Hypertension

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Author(s): B.W. Nileeka Balasuriya | H.P. Vasantha Rupasinghe

Journal: Functional Foods in Health and Disease
ISSN 2160-3855

Volume: 5;
Issue: May;
Start page: 172;
Date: 2011;
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Keywords: Hypertension | renin angiotensin system (RAS) | angiotensin converting enzyme (ACE)

ABSTRACT
Background: Angiotensin converting enzyme (ACE) is a key component in the renin angiotensin aldosterone system (RAAS) which regulates blood pressure. As the over expression of RAAS is associated with vascular hypertension, ACE inhibition has become a major target control for hypertension. The research on potential ACE inhibitors is expanding broadly and most are focused on natural product derivatives such as peptides, polyphenolics, and terpenes. Plant polyphenolics are antioxidant molecules with various beneficial pharmacological properties. The current study is focused on investigating and reviewing the ACE inhibitory property of fruit flavonoids. An apple skin extract (ASE) rich in flavonoids, the major constituents of the extract and their selected metabolites were assessed for the ACE inhibitory property in vitro. It is important to investigate the metabolites along with the flavonoids as they are the constituents active inside the human body.Objective: To investigate whether flavonoids, flavonoid rich apple extracts and their metabolites could inhibit ACE in vitro.Method: The samples were incubated with sodium borate buffer (30 μL, pH 8.3), 150 μL of substrate (Hip-His-Liu) and ACE (30 μL) at 37 oC for 1 h. The reaction was stopped by addition of 150 μL of 0.3M NaOH. The enzyme cleaved substrate was detected by making a fluorimetricadduct by adding 100 μL of o-phthaladehyde for 10 min at room temperature. Reaction wasstopped by adding 50 μL of 3M HCl. Fluorescence was measured by using a FluoStar Optimaplate reader at excitation of 350 nm and emission of 500 nm.Results: The extract and the compounds showed a concentration dependant enzyme inhibition.Increasing concentrations from 0.001 ppm to 100 ppm of ASE showed an increment of 29% to64% ACE inhibition. The IC50 (concentration of test compound which gives 50% enzymeinhibition) values of ASE, quercetin, quercetin-3-glucoside, quercetin-3-galactoside, cyanidin-3-galactoside were 49 μg/mL, 151 μM, 71 μM, 180 μM, 206 μM, respectively. The majorconstituents of the ASE that were tested separately showed effective ACE inhibition. From thethree metabolites tested, only quercetin-3-glucuronic acid showed concentration dependant ACEinhibition. The ACE inhibition of 0.001 ppm to 100 ppm of quercetin-3-glucuronic was in therange of 43% and 75% and the IC50 value was 27 μM.Conclusion: The results demonstrated that flavonoids have a potential to inhibit ACE in vitroand the inhibitory property varies according to type of sugar moiety attached at C-3 position. Theresults also revealed that the major contributing compounds of ASE for ACE inhibition belong toflavonoids. Among the tested compounds, the lowest IC50 value is associated with the quercetin-3-glucuronic acid, a major in vivo metabolites of quercetin and its glycosides. The results suggestthat certain dietary flavonoids may possess properties of blood pressure regulation.
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