Multifunctional Peptides from Spanish Dry-Cured Pork Ham: Endothelial Responses and Molecular Modeling Studies

Abstract

Food peptides contain a very wide range of diversified structures, which explains their diverse range of functional activities. Proatherogenic endothelium is related to vasoconstriction, inflammation, and oxidative stress. In this line, four synthetic bioactive peptides from dry-cured pork ham, previously identified according to their Angiotensin I Converting Enzyme (ACE) inhibitory capacity and high bioavailability, were tested. Among them, KPVAAP displayed an estimated IC50 of 59.22 µM for human ACE inhibition, and docking simulations demonstrated the consistency of the noncompetitive binding with the protein. The addition of synthetic peptides to human endothelial cells significantly prevents the expression of genes related to endothelial dysfunction and inflammation (eNOS, ICAM-1, VCAM-1, IL-6) and lowers NF-κB activation (all p < 0.05). In silico dockings showed that the four bioactive peptides interact with the regulatory subunit NEMO of the NF-κB transcription factor at the same site as other characterized inhibitors (CC2-LZ region). This is the first study linking experimental and computational approaches that shows NF-κB to be the target of biopeptides of food origin. These multifunctional peptides from dry-cured pork ham make them good candidates for further research into their therapeutic or preventive use to attenuate the inflammatory atherosclerotic process.

Trends in In Silico Approaches to the Prediction of Biologically Active Peptides in Meat and Meat Products as an Important Factor for Preventing Food-Related Chronic Diseases

“…Docking simulations were also carried out using ACE and different peptides from dry-cured pork ham. Molecular modeling showed that KPVAAP, KAAAATP, and KPGRP are stabilized by both hydrogen and hydrophobic interactions with at least one residue of the three pockets, which is consistent with the typical competitive inhibition model [24]. Moreover, two novel ACE inhibitory peptides (EACF and CDF) were screened from rabbit meat proteins using in silico methods.…”

“…Computer simulations and molecular docking are also possible using bioinformatics tools. This approach is particularly helpful for assessing the complementarity of a selected peptide sequence to the active site of a molecule, most often an enzyme to inactivate it, as was the case, for example, with the peptide, ACE-I, or DPP-IV inhibitors [24][25][26][27][28][29]. By using the molecular model of the enzyme and the peptide molecule, it is possible to evaluate the possibilities of them docking each other without the need for laboratory analyses.…”

Bioactive and Sensory Di- and Tripeptides Generated during Dry-Curing of Pork Meat

“…It has been proved that peptides generated from endogenous muscle proteins during dry-curing of ham exert in vitro angiotensin I-converting enzyme (ACE-I) inhibitory activity, antioxidant activity, dipeptidyl peptidase IV (DPP-IV), α-glucosidase inhibitory activity, antioxidant, anti-hyperglycemic, anti-inflammatory, and antilisterial activities [ 91 , 119 , 120 , 121 , 122 ]. In fact, some in vivo and interventional studies have also been conducted, demonstrating antihypertensive and anti-inflammatory potential [ 123 , 124 , 125 , 126 , 127 ].…”

Beneficial Impact of Pork Dry-Cured Ham Consumption on Blood Pressure and Cardiometabolic Markers in Individuals with Cardiovascular Risk

“…Occasional consumption is recommended due to its moderate salt content despite the fact that it provides a varied amount of important nutrients and other bioactive compounds of interest [8]. The in vitro inhibitory capacities of bioactive peptides of this product have been previously reported for distinct enzymes and have been further tested in human cells and in mice by our groups [9][10][11][12]. Further, in a previous clinical study, our group already investigated the effects of consumption of dry-cured ham in healthy adults with normal-high systolic BP.…”