Multifunctional Analysis of Chia Seed (Salvia hispanica L.) Bioactive Peptides Using Peptidomics and Molecular Dynamics Simulations Approaches

Abstract

Chia seed peptides (CSP) can be a source of multifunctional biopeptides to treat non-communicable diseases. However, interactions and binding affinity involved in targeting specific receptors remains unexplored. In this study, molecular simulation techniques were used as virtual screening of CSP to determine drug-like candidates using a multi-target-directed ligand approach. CSP fraction with the best bioactivities in vitro was sequenced. Then, a prediction model was built using physicochemical descriptors (hydrophobicity, hydrophilicity, intestinal stability, antiangiogenic, antihypertensive, and anti-inflammatory) to calculate potential scores and rank possible biopeptides. Furthermore, molecular dynamics simulations (MDS) and ensemble molecular docking analysis were carried out using four human protein targets (ACE, angiotensin converting enzyme; VEGF, vascular endothelial growth factor; GLUC, glucocorticoid and MINC, mineralocorticoid receptors). Five known-sequence peptides (NNVFYPF, FNIVFPG, SRPWPIDY, QLQRWFR, GSRFDWTR) and five de novo peptides (DFKF, DLRF, FKAF, FRSF, QFRF) had the lowest energy score and higher affinity for ACE and VEGF. The therapeutic effects of these selected peptides can be related to the inhibition of the enzymes involved in angiogenesis and hypertension, due to formation of stable complexes with VEGF and ACE binding sites, respectively. The application of MDS is a good resource for identifying bioactive peptides for future experimental validation.

Identification of the Bioavailable Peptidome of Chia Protein Hydrolysate and the In Silico Evaluation of Its Antioxidant and ACE Inhibitory Potential

“…These sequences are able to cross the intestinal barrier without suffering any kind of modification, as explained previously. For instance, of the three peptides similar to NNVFYPF, two (RNNVFYPFE and RNNVFYPF) were identified as bioavailable in our research, whereas RNNVFYPFD demonstrated that it did not cross the barrier or was not identified in a sufficient amount.…”

“…However, there is only recently published literature reporting the identification of peptides from chia. For instance, five sequence peptides (NNVFYPF, FNIVFPG, SRPWPIDY, QLQRWFR, and GSRFDWTR) were identified by Aguilar-Toalá et al Similar to NNVFYPF, in the original hydrolysate, the peptides RNNVFYPFD, RNNVFYPFE, and RNNVFYPF were identified. Similarly, other peptides containing those identified by these authors were found in the hydrolysate under assessment and will be further discussed in the following sections.…”

“…Research on bioactive peptides derived from chia demonstrate antibacterial, angiotensin converting enzyme (ACE) inhibitors, and antioxidant properties in vitro, among others. In addition, analysis employing cell culture or rats increase the evidence that these peptides can modulate the physiological status of human beings.…”

Lactobacillus casei-Derived Postbiotics Elevate the Bioaccessibility of Proteins via Allosteric Regulation of Pepsin and Trypsin and Introduction of Endopeptidases

“…13 Infant formulae are also increasingly supplemented with prebiotics, probiotics, and synbiotics despite uncertainties regarding their efficacy, and a number of studies associated with the exploitation of products supplemented with probiotic/prebiotic for infants have been published in recent years. 14,15 Several clinical benefits of supplementation of infant or followon formula with single or combination probiotics , especially given beyond early infancy, had also been reported, specifically including reducing the frequency and intensity of colic and/or irritability, decreasing the risk of antibiotic use, and reducing the risk of nonspecific gastrointestinal infections by enhancing intestinal colonization of probiotics and elevating food digestibility. 16 However, a potential problem using live probiotic cells for health regulation is that they may cause some pathological changes, especially in immunodeficient patients.…”

“…The results of the Lactobacillus and Bacillus subtilis supplementation on growth performance, apparent nutrient digestibility, and stress-related indicators in dairy calves indicated that oral administration of Lactobacillus apparently improved the digestibility of crude protein . Infant formulae are also increasingly supplemented with prebiotics, probiotics, and synbiotics despite uncertainties regarding their efficacy, and a number of studies associated with the exploitation of products supplemented with probiotic/prebiotic for infants have been published in recent years. , Several clinical benefits of supplementation of infant or follow-on formula with single or combination probiotics , especially given beyond early infancy, had also been reported, specifically including reducing the frequency and intensity of colic and/or irritability, decreasing the risk of antibiotic use, and reducing the risk of nonspecific gastrointestinal infections by enhancing intestinal colonization of probiotics and elevating food digestibility …”