Protection against Oxidative Stress and Metabolic Alterations by Synthetic Peptides Derived from Erythrina edulis Seed Protein

Abstract

The ability of multifunctional food-derived peptides to act on different body targets make them promising alternatives in the prevention/management of chronic disorders. The potential of Erythrina edulis (pajuro) protein as a source of multifunctional peptides was proven. Fourteen selected synthetic peptides identified in an alcalase hydrolyzate from pajuro protein showed in vitro antioxidant, anti-hypertensive, anti-diabetic, and/or anti-obesity effects. The radical scavenging properties of the peptides could be responsible for the potent protective effects observed against the oxidative damage caused by FeSO₄ in neuroblastoma cells. Moreover, their affinity towards the binding cavity of angiotensin-converting enzyme (ACE) and dipeptidyl peptidase IV (DPP-IV) were predicted by molecular modeling. The results demonstrated that some peptides such as YPSY exhibited promising binding at both enzymes, supporting the role of pajuro protein as a novel ingredient of functional foods or nutraceuticals for prevention/management of oxidative stress, hypertension, and metabolic-alteration-associated chronic diseases.

Keywords: Erythrina edulis; antioxidant activity; legume proteins; molecular docking; multifunctional peptides.

Figure 1

ROS levels (% of control) after the pre-treatment of SH-SY5Y cells with peptides (A) DGLGYY; (B) AALWE; (C) CCGDYY; (D) YPSY; (E) SQLPGW; (F) MFTGPY at different concentrations (25, 50, and 100 µM) for 3 h, and induction with FeSO₄. * p < 0.05, ** p < 0.001 vs. control (non-treated cells), # p < 0.001 vs. FeSO₄ treated cells.

Figure 2

(A) MDA levels (nmol/mg protein) after the treatment of SH-SY5Y cells with FeSO₄ in the absence and presence of 100 µM of pajuro peptides; (B) LDH activity (% of control) after the treatment of SH-SY5Y cells with FeSO₄ in the absence and presence of 100 µM of pajuro peptides; (C) protein carbonyls levels (nmol/mg protein) after the treatment of SHSY5Y cells with FeSO₄ in the absence and presence of YPSP and SQLPGW different concentrations (25, 50, and 100 uM). * p < 0.05 or ** p < 0.001 vs. control (non-treated cells), # p < 0.001 vs. FeSO₄ treated cells.

Figure 3

Molecular interactions between ACE-I and pajuro peptides after model structure refinement. (A) Representation of the SQLPGW peptide at physiological pH and its electrostatic potential isosurface showing negatively and positively charged regions in red and blue, respectively. (B) Side view (bottom) of the ACE-I pocket to illustrate the subsite occupancy by pajuro peptides. For pajuro peptides, only the backbone chain is shown, a chain with blue color corresponds to SQLPGW peptide, orange to DGLGYY peptide, and orange chain to YPSY peptide. Enalaprilat inhibitor atoms are shown explicitly in this representation. The figure also explicitly shows atoms of side chains from residues with higher contribution to ΔG binding according to in silico alanine scanning. (C) Heat map showing the ΔG binding contributions of ACE-I residues to their binding to pajuro peptides according to in silico alanine scanning using a DRUGSCOREPPI web server based on a knowledge-based scoring function. The name of residues with higher contributions are bold black, residues expected to have higher contributions in good ACE-I inhibitors are bold red.

Figure 4

Molecular interactions between DPP-IV and pajuro peptides after model structure refinement. (A) Representation of the YPSY peptide at physiological pH and its electrostatic potential isosurface showing negatively and positively charged regions in red and blue, respectively. (B) Side view (bottom) of the DPP-IV pocket to illustrate the occupancy by pajuro peptides. For pajuro peptides, only the backbone chain is shown; chains with blue color correspond to YPSY peptide, orange to AALWE peptide, orange chains to MFTGPY peptide, and green chains to diprotin A inhibitor. The figure also explicitly shows side chains of residues with higher contribution to ΔG binding according to in silico alanine scanning. (C) Heat map showing the ΔG binding contributions of DPP-IV residues to their binding to pajuro peptides according to in silico alanine scanning using DRUGSCOREPPI web server based on a knowledge-based scoring function. The name of residues with higher contributions are bold black.