In vitro and in silico studies of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitory activity of the cowpea Gln-Asp-Phe peptide

Silva, Mariana Barros de Cerqueira e; Souza, Caio Alexandre da Cruz; Philadelpho, Biane Oliveira; Cunha, Mariana Mota Novais da; Batista, Fabiana Pacheco Reis; Silva, Jaff Ribeiro da; Druzian, Janice Izabel; Castilho, Marcelo Santos; Cilli, Eduardo Maffud; Ferreira, Ederlan de Souza

doi:10.1016/j.foodchem.2018.03.132

Cited by 27 publications

(23 citation statements)

References 32 publications

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“…Interestingly, EE was found to present an inhibition constant of the same order of units as pravastatin (569.34 nM), while the rest of the dipeptides showed micromolar units. Similar binding constant units and/or modulating mechanisms have been previously described with peptides such as QDF derived from cowpea β-vignin protein, and the synthetic peptide GFPTGG, caprine milk-derived sequences NMAIHPR, TNAIPVYR and TNAIPYVRL, and soy β-conglycininderived peptides YVVNPDNDEN and YVVNPDNNEN (Fatchiyah & Natasia 2018;Lammi et al 2015;Lammi et al 2016a, b;Pak et al 2007;Silva et al 2018;Zanoni et al 2017).…”

Section: Docking Resultssupporting

confidence: 59%

Inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase enzyme by dipeptides identified in dry-cured ham

Heres

Mora

2021

Food Prod Process and Nutr

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High cholesterolemia is a key risk factor for the development of cardiovascular diseases, which are the main cause of mortality in developed countries. Most therapies are focused on the modulation of its biosynthesis through 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR) inhibitors. In this sense, food-derived bioactive peptides might act as promising health alternatives through their ability to interact with crucial enzymes involved in metabolic pathways, avoiding the adverse effects of synthetic drugs. Dry-cured ham has been widely described as an important source of naturally-generated bioactive peptides exerting ACEI-inhibitory activity, antioxidant activity, and anti-inflammatory activity between others. Based on these findings, the aim of this work was to assess, for the first time, the in vitro inhibitory activity of HMG-CoAR exerted by dipeptides generated during the manufacturing of dry-cured ham, previously described with relevant roles on other bioactivities.The in vitro inhibitory activity of the dipeptides was assessed by measuring the substrate consumption rate of the 3-hydroxy-3-methylglutaryl CoA reductase in their presence, with the following pertinent calculations.Further research was carried out to estimate the possible interactions of the most bioactive dipeptides with the enzyme by performing in silico analysis consisting of molecular docking approaches.Main findings showed DA, DD, EE, ES, and LL dipeptides as main HMG-CoAR inhibitors. Additionally, computational analysis indicated statin-like interactions of the dipeptides with HMG-CoAR.This study reveals, for the first time, the hypocholesterolemic potential of dry-cured ham-derived dipeptides and, at the same time, converges in the same vein as many reports that experimentally argue the cardiovascular benefits of dry-cured ham consumption due to its bioactive peptide content.

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Section: Docking Resultssupporting

confidence: 59%

Inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase enzyme by dipeptides identified in dry-cured ham

Heres

Mora

2021

Food Prod Process and Nutr

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“…In addition, BIOPEP-UWM provides an abundance of information on peptides as antidiabetic (DPP-IV, α-glucosidase, of α-amylase), antioxidant, HMG-CoA reductase inhibitor activities, etc. [2,72,111,113,116,117]. The activity prediction of a peptide is calculated based on two quantitative parameters, namely the occurrence frequency value (A) and a potential biological activity (B) [111].…”

Section: In Silico Prediction Of Potential Dpp-iv Inhibitory Peptidesmentioning

confidence: 99%

Characteristics of Food Protein-Derived Antidiabetic Bioactive Peptides: A Literature Update

Nong

Hsu

2021

IJMS

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Diabetes, a glucose metabolic disorder, is considered one of the biggest challenges associated with a complex complication of health crises in the modern lifestyle. Inhibition or reduction of the dipeptidyl peptidase IV (DPP-IV), alpha-glucosidase, and protein-tyrosine phosphatase 1B (PTP-1B) enzyme activities or expressions are notably considered as the promising therapeutic strategies for the management of type 2 diabetes (T2D). Various food protein-derived antidiabetic bioactive peptides have been isolated and verified. This review provides an overview of the DPP-IV, PTP-1B, and α-glucosidase inhibitors, and updates on the methods for the discovery of DPP-IV inhibitory peptides released from food-protein hydrolysate. The finding of novel bioactive peptides involves studies about the strategy of separation fractionation, the identification of peptide sequences, and the evaluation of peptide characteristics in vitro, in silico, in situ, and in vivo. The potential of bioactive peptides suggests useful applications in the prevention and management of diabetes. Furthermore, evidence of clinical studies is necessary for the validation of these peptides’ efficiencies before commercial applications.

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“…Several studies have proposed that bioactive peptides, particularly those of legume seed origin, represent a possible alternative to statin drugs [13][14][15][16][17], as well as other natural compounds (salvianolic acid, curcumin, and docosanol) [18]. The cholesterol-lowering properties of some of these peptides have been demonstrated in vitro and in vivo [19][20][21]. However, the mechanisms by which they exert these effects have not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

IAF, QGF, and QDF Peptides Exhibit Cholesterol-Lowering Activity through a Statin-like HMG-CoA Reductase Regulation Mechanism: In Silico and In Vitro Approach

Silva

Philadelpho

Santos

et al. 2021

IJMS

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In this study, in silico approaches are employed to investigate the binding mechanism of peptides derived from cowpea β-vignin and HMG-CoA reductase. With the obtained information, we designed synthetic peptides to evaluate their in vitro enzyme inhibitory activity. In vitro, the total protein extract and <3 kDa fraction, at 5000 µg, support this hypothesis (95% and 90% inhibition of HMG-CoA reductase, respectively). Ile-Ala-Phe, Gln-Gly-Phe, and Gln-Asp-Phe peptides were predicted to bind to the substrate binding site of HMGCR via HMG-CoAR. In silico, it was established that the mechanism of HMG-CoA reductase inhibition largely entailed mimicking the interactions of the decalin ring of simvastatin and via H-bonding; in vitro studies corroborated the predictions, whereby the HMG-CoA reductase activity was decreased by 69%, 77%, and 78%, respectively. Our results suggest that Ile-Ala-Phe, Gln-Gly-Phe, and Gln-Asp-Phe peptides derived from cowpea β-vignin have the potential to lower cholesterol synthesis through a statin-like regulation mechanism.

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In vitro and in silico studies of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitory activity of the cowpea Gln-Asp-Phe peptide

Cited by 27 publications

References 32 publications

Inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase enzyme by dipeptides identified in dry-cured ham

Inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase enzyme by dipeptides identified in dry-cured ham

Characteristics of Food Protein-Derived Antidiabetic Bioactive Peptides: A Literature Update

IAF, QGF, and QDF Peptides Exhibit Cholesterol-Lowering Activity through a Statin-like HMG-CoA Reductase Regulation Mechanism: In Silico and In Vitro Approach

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