Special Issue "Peptides for Health Benefits 2021".

In recent years, non-communicable diseases (NCDs) have increased in prevalence in our society and have become a serious burden of disease worldwide [...].

Contribution of Proteins and Peptides to the Impact of a Soy Protein Isolate on Oxidative Stress and Inflammation-Associated Biomarkers in an Innate Immune Cell Model.

The innate and adaptative immune systems are involved in the regulation of inflammatory and oxidative processes and mediators such as reactive oxygen species (ROS) and nitric oxide (NO). The exacerbated action of these players results in an oxidative stress status and chronic inflammation, which is responsible for the development of non-communicable diseases (NCDs). By modulating these mediators, bioactive compounds in food can exert a key role in the prevention of several NCDs. Among these compounds, soybean proteins and peptides such as lunasin have been considered to be among the most promising. The aim of this study was to obtain and characterize a soluble protein-enriched extract from a commercial soybean protein isolate and fractionate it into different fractions through ultrafiltration. Their antioxidant and immunomodulatory properties were then evaluated using biochemical and cell models. A total of 535 proteins (from 282 protein groups) were identified in the extract, in which the presence of the peptide lunasin was confirmed. The enrichment of this peptide was achieved in the 3-10 kDa fraction. The protective effects against the oxidative stress induced by LPS in the macrophage model could have been mediated by the radical scavenging capacity of the peptides present in the soybean samples. Under basal conditions, the extract and its ultrafiltered fractions activated macrophages and induced the release of NO. However, under challenged conditions, the whole extract potentiated the NO-stimulating effects of LPS, whereas the fraction containing 3-10 kDa peptides, including lunasin, counteracted the LPS-induced NO increase. Our findings suggest a promising role of soybean protein as an ingredient for functional foods and nutraceuticals aimed at promoting health and preventing oxidative stress and/or immune-alteration-associated diseases.

Isolation and Characterization of Protein Fractions for Valorization of Sacha Inchi Oil Press-Cake.

The growing interest in plant-based food protein sources has provided opportunities for the valorization of agri-food by-products, driving the food industry towards more sustainable development. In this study, three extraction procedures (varying the pH value (7.0 and 11.0) and the addition of salt (0 and 5%)) were investigated to obtain seven different protein fractions (SIPF) from Sacha Inchi oil press-cake (SIPC), which were characterized in terms of their protein content, electrophoretic profile, secondary structure, and techno-functional properties. Extractions at pH 11.0 without salt addition produced the highest values of protein content, extraction yield, protein recovery, and protein concentration increase (84.0%, 24.7%, 36.5%, and 1.5-fold, respectively). Under these extraction conditions, the electrophoretic analysis indicated that most of the SIPC proteins were extracted. SIPF displayed an excellent oil absorption capacity (4.3-9.0 w/w), and interesting foam activity (36.4-133.3%). The solubility and emulsifying activity of the albumin fractions were significantly higher than those of the other fractions (~87 vs. <15.8%, and 280-370 vs. <140 m2/g, respectively). Correlation analysis showed that the secondary structure of the SIPF significantly influences their techno-functional properties. These results indicate that SIPC is a by-product of great potential for protein extraction processes, and as a valorization strategy for technical cycle solutions for the Sacha Inchi productive chain in the circular economy context.

Evaluation of the Multifunctionality of Soybean Proteins and Peptides in Immune Cell Models.

Inflammatory and oxidative processes are tightly regulated by innate and adaptive immune systems, which are involved in the pathology of a diversity of chronic diseases. Soybean peptides, such as lunasin, have emerged as one of the most hopeful food-derived peptides with a positive impact on health. The aim was to study the potential antioxidant and immunomodulatory activity of a lunasin-enriched soybean extract (LES). The protein profile of LES was characterized, and its behavior under simulated gastrointestinal digestion was evaluated. Besides its in vitro radical scavenging capacity, LES and lunasin's effects on cell viability, phagocytic capacity, oxidative stress, and inflammation-associated biomarkers were investigated in both RAW264.7 macrophages and lymphocytes EL4. Lunasin and other soluble peptides enriched after aqueous solvent extraction partially resisted the action of digestive enzymes, being potentially responsible for the beneficial effects of LES. This extract scavenged radicals, reduced reactive oxygen species (ROS) and exerted immunostimulatory effects, increasing nitric oxide (NO) production, phagocytic activity, and cytokine release in macrophages. Lunasin and LES also exerted dose-dependent immunomodulatory effects on EL4 cell proliferation and cytokine production. The modulatory effects of soybean peptides on both immune cell models suggest their potential protective role against oxidative stress, inflammation, and immune response-associated disorders.

Exploration of the Nutritional and Functional Properties of Underutilized Grains as an Alternative Source for the Research of Food-Derived Bioactive Peptides.

The estimated increase in world population will lead to a deterioration in global food security, aggravated in developing countries by hidden hunger resulting from protein deficiency. To reduce or avoid this crisis, a dietary shift towards the consumption of sustainable, nutrient-rich, and calorically efficient food products has been recommended by the FAO and WHO. Plant proteins derived from grains and seeds provide nutritionally balanced diets, improve health status, reduce poverty, enhance food security, and contain several functional compounds. In this review, the current evidence on the nutritional and functional properties of underutilized grains is summarized, focusing on their incorporation into functional foods and the role of their proteins as novel source of bioactive peptides with health benefits.

Bioactivity and Digestibility of Microalgae Tetraselmis sp. and Nannochloropsis sp. as Basis of Their Potential as Novel Functional Foods.

It is estimated that by 2050, the world's population will exceed 10 billion people, which will lead to a deterioration in global food security. To avoid aggravating this problem, FAO and WHO have recommended dietary changes to reduce the intake of animal calories and increase the consumption of sustainable, nutrient-rich, and calorie-efficient products. Moreover, due to the worldwide rising incidence of non-communicable diseases and the demonstrated impact of diet on the risk of these disorders, the current established food pattern is focused on the consumption of foods that have functionality for health. Among promising sources of functional foods, microalgae are gaining worldwide attention because of their richness in high-value compounds with potential health benefits. However, despite the great opportunities to exploit microalgae in functional food industry, their use remains limited by challenges related to species diversity and variations in cultivation factors, changes in functional composition during extraction procedures, and limited evidence on the safety and bioavailability of microalgae bioactives. The aim of this review is to provide an updated and comprehensive discussion on the nutritional value, biological effects, and digestibility of two microalgae genera, Tetraselmis and Nannochloropsis, as basis of their potential as ingredients for the development of functional foods.

Release of Bioactive Peptides from Erythrina edulis (Chachafruto) Proteins under Simulated Gastrointestinal Digestion.

The estimated and concerning rise in world population over the next few years and the consequent increase in food demand will lead to a deterioration in global food security. To avoid or reduce this world crisis, informed and empowered consumers are turning to sustainable and nutrient-rich foods that substitute animal products, also reducing their associated environmental impact. Moreover, due to the demonstrated influence of diet on the risk of high incidence and mortality of noncommunicable diseases, the current established food pattern is focused on the consumption of foods that have functionality for health. Among these new foods, traditional and underutilized plants are gaining interest as alternative protein sources providing nutritional and biological properties. In this work, the potential of Erythrina edulis (chachafruto) proteins as a source of multifunctional peptides after transit through the gastrointestinal tract has been demonstrated, with antioxidant and immunostimulating effects in both biochemical assays and cell culture. While low molecular weight peptides released during the digestive process were found to be responsible for protection against oxidative stress mediated by their radical scavenging activity, high molecular weight peptides exerted immunostimulating effects by upregulation of immunoresponse-associated biomarkers. The findings of this study support the promising role of chachafruto proteins as a new antioxidant and immunostimulatory ingredient for functional foods and nutraceuticals.

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

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.

Lunasin as a Promising Plant-Derived Peptide for Cancer Therapy.

Cancer has become one of the main public health problems worldwide, demanding the development of new therapeutic agents that can help reduce mortality. Lunasin is a soybean peptide that has emerged as an attractive option because its preventive and therapeutic actions against cancer. In this review, we evaluated available research on lunasin's structure and mechanism of action, which should be useful for the development of lunasin-based therapeutic products. We described data on its primary, secondary, tertiary, and possible quaternary structure, susceptibility to post-translational modifications, and structural stability. These characteristics are important for understanding drug activity and characterizing lunasin products. We also provided an overview of research on lunasin pharmacokinetics and safety. Studies examining lunasin's mechanisms of action against cancer were reviewed, highlighting reported activities, and known molecular partners. Finally, we briefly discussed commercially available lunasin products and potential combination therapeutics.

Peptides for Health Benefits 2020.

In recent years, peptides have received increased interest in pharmaceutical, food, cosmetics, and various other fields [...].

Temporal changes in salivary composition induced by oral exposure to different wine matrices and the relationship with the behaviour of aroma compounds in the mouth.

The dynamic changes in saliva flow and composition (pH, total protein capacity (TPC), total polyphenol index (TPI) and saliva antioxidant activity (SAOX)) after the exposure of the oral cavity to aromatized wine matrices with different chemical compositions (dealcoholized, alcoholized, and synthetic wines) have been investigated. For this, stimulated saliva from ten volunteers were collected five days per week (from Monday to Friday) during three non-consecutive weeks, before (basal saliva) and after the oral intervention with the wines (5 and 15 minutes later) (n = 450). In order to know the relationship between the changes induced in salivary composition and the amount of aroma retained in the oral cavity, the expectorated wines were also collected (n = 150). Results showed differences in saliva composition (pH, TPI and SAOX) depending on the wine matrix that were only significant in the first five minutes after the oral exposure to the wines. The wines with ethanol produced significantly lower in-mouth aroma retention, while salivary TPI and, to a minor extent, SAOX, were positively related to the aroma retained. These results prove that not only wine aroma composition, but also the physiological changes in saliva induced by the non-volatile chemical composition of the wine play an important role in wine odorant compounds, and likely, in aroma perception.

Albumin from Erythrina edulis (Pajuro) as a Promising Source of Multifunctional Peptides.

Multifunctional peptides, capable of acting on different body systems through multiple mechanisms of action, offer many advantages over monofunctional peptides, including lower adverse side effects and costs. Erythrina edulis (pajuro) is a legume with a large number of high-quality proteins, of which their potential as a source of antioxidant peptides has been recently reported. In this study, the behavior of these proteins under a sequential enzymatic hydrolysis with digestive and microbial enzymes was investigated by evaluating the multi-functionality of the hydrolyzates. The albumin hydrolyzates obtained after the action of pepsin, pancreatin, and Alcalase showed antioxidant, angiotensin-converting enzyme (ACE), α-amylase, α-glucosidase, and dipeptidyl peptidase (DPP)-IV inhibitory activities. The radical scavenging properties of the hydrolyzate could be responsible for the potent protective effects observed in FeSO4-induced neuroblastoma cells. The findings support the role of pajuro protein as an ingredient of functional foods or nutraceuticals for health promotion and the prevention of oxidative stress, hypertension, and metabolic alteration-associated chronic diseases.

Cocoa (Theobroma cacao L.) Seed-Derived Peptides Reduce Blood Pressure by Interacting with the Catalytic Site of the Angiotensin-Converting Enzyme.

This study aimed at determining the effect of cocoa proteins (CP) on the blood pressure, using in silico, in vitro and in vivo approaches. The in silico assay showed 26 Criollo cocoa peptides with alignment in the Blast® analysis. Peptide sequences ranged from 6 to 16 amino acids, with molecular weight ranging from 560.31 to 1548.76 Da. The peptide sequences LSPGGAAV, TSVSGAGGPGAGR, and TLGNPAAAGPF showed the highest theoretical affinity with -8.6, -5.0, and -10.2 kcal/mol, for the angiotensin-converting enzyme (ACE), renin, and angiotensin II type 1 receptor (AT1-R), respectively. The Criollo CP hydrolysates (CPH) presented in vitro ACE inhibitory activity with an IC50 value of 0.49 mg/mL. Furthermore, the orogastric administration of 150 mg CP/kg/day in rats fed a high-fat (HF) diet (HF + CP group) showed a significant decrease in systolic blood pressure (SBP) by 5% (p < 0.001) and diastolic blood pressure (DBP) by 7% (p < 0.001) compared with the HF group. The human equivalent dose (HED) of CP for an adult (60 kg) is 1.45 g per day. These results suggest that the consumption of CP could reduce blood pressure by blocking ACE, and could be used as an ingredient in the elaboration of antihypertensive functional foods.

Lunasin Peptide is a Modulator of the Immune Response in the Human Gastrointestinal Tract.

INTRODUCTION: Lunasin is a soybean bioactive peptide with a variety of beneficial properties against chronic disorders. However, its effect in human primary intestinal cells remains unknown. Hence, this study aims to characterize its ex vivo biological activity in the human intestinal mucosa. METHODS AND RESULTS: Human intestinal biopsies, obtained from healthy controls, are ex vivo conditioned with lunasin both in the presence/absence of lipopolysaccharide (LPS). Peptide maintains its stability during biopsy culture by HPLC-MS/MS analysis. Lunasin is bioactive in the human mucosa, as it induces IL-1ß, TNF-α, IL-17A, CCL2, and PGE2/COX-2 gene expression together with an increased expression of tolerogenic IL-10 and TGFß, while it also downregulates the expression of iNOS and subunit p65 from NF-κB. Indeed, lunasin also abrogates the LPS-induced pro-inflammatory response, downregulating IL-17A, IFNγ, and IL-8 expression, and inducing IL-10 and TGFß expression. These results are also mirrored in the cell-free culture supernatants at the protein level by Multiplex. Moreover, lunasin further induces a regulatory phenotype and function on human intestinal conventional dendritic cell and macrophage subsets as assessed by flow cytometry. CONCLUSIONS: We hereby have characterized lunasin as an immunomodulatory peptide with potential capacity to prevent immune and inflammatory-mediated disorders in the human gastrointestinal tract.

Associations of Salivary Total Antioxidant Capacity With Cortical Amyloid-Beta Burden, Cortical Glucose Uptake, and Cognitive Function in Normal Aging.

BACKGROUND: Determining susceptibility to Alzheimer's disease (AD) in asymptomatic individuals requires from noninvasive, simple, and inexpensive markers that can be easily obtained in primary care settings. While saliva meets all these requirements, there is a lack of evidence linking salivary constituents to in vivo AD pathology in aging. METHODS: We examined the potential of salivary total antioxidant capacity (TAC) for identifying global cortical amyloid-beta (Aß) burden, deficits in regional glucose uptake, and poorer cognition in 71 cognitively normal older adults. We further assessed whether salivary TAC-related cognitive performance was associated with higher Aß load and lower cortical glucose consumption. RESULTS: Linear regression analyses adjusted by age, sex, years of education, and ApoE4 status showed that salivary TAC was associated with slower processing speed and poorer sustained attention, as well as with higher Aß load and lower glucose metabolism in cortical regions vulnerable to cognitive aging and AD. Results also revealed that lower scores in processing speed and sustained attention were associated with greater Aß burden and lower regional glucose consumption, respectively. CONCLUSIONS: Together, these findings support the use of salivary TAC for preventive screening and detection of cerebral vulnerability to AD. Further research is needed to evaluate the utility of salivary TAC as a clinical marker.

Introduction to the Special Issue: New Advances in the Research of Antioxidant Food Peptides.

During cell metabolism, oxygen is partially reduced to reactive oxygen species (ROS) that play a physiological role in cellular processes, including proliferation, cell cycle and death, and signal transduction [...].

Current Evidence on the Bioavailability of Food Bioactive Peptides.

Food protein-derived bioactive peptides are recognized as valuable ingredients of functional foods and/or nutraceuticals to promote health and reduce the risk of chronic diseases. However, although peptides have been demonstrated to exert multiple benefits by biochemical assays, cell culture, and animal models, the ability to translate the new findings into practical or commercial uses remains delayed. This fact is mainly due to the lack of correlation of in vitro findings with in vivo functions of peptides because of their low bioavailability. Once ingested, peptides need to resist the action of digestive enzymes during their transit through the gastrointestinal tract and cross the intestinal epithelial barrier to reach the target organs in an intact and active form to exert their health-promoting properties. Thus, for a better understanding of the in vivo physiological effects of food bioactive peptides, extensive research studies on their gastrointestinal stability and transport are needed. This review summarizes the most current evidence on those factors affecting the digestive and absorptive processes of food bioactive peptides, the recently designed models mimicking the gastrointestinal environment, as well as the novel strategies developed and currently applied to enhance the absorption and bioavailability of peptides.

Cocoa (Theobroma cacao L.) Seed Proteins' Anti-Obesity Potential through Lipase Inhibition Using In Silico, In Vitro and In Vivo Models.

The aim of this study was to determine the pancreatic lipase (PL) inhibitory effect of cocoa protein (CP) hydrolysates (CPH) using in silico and in vitro approaches, and an in vivo high-fat diet (HF) obese rat model. The results showed better theoretical affinity on PL for cocoa peptides EEQR, GGER, QTGVQ, and VSTDVNIE released from vicilin and albumins (-6.5, -6.3, -6.2, and -6.1 kcal/mol, respectively). Absorption, distribution, metabolism, and excretion (ADMET) prediction showed the human intestinal absorption (HIA) capacity of orlistat and eight cocoa peptides, demonstrating that they presented a low probability of toxicity with values lower than 0.6, while the orlistat has a high probability of hepatotoxicity with a mean value of 0.9. CPH (degree of hydrolysis of 55%) inhibited PL with an IC50 (concentration needed to inhibit 50% of enzyme activity) value of 1.38 mg/mL. The intragastric administration of 150 mg CP/kg/day to rats increased total lipids and triglycerides excretion in feces, ranging from 11% to 15% compared to the HF-diet. The HF + CP-diet also significantly decreased (p < 0.05) the apparent rate of fat absorption compared with the HF group. These results suggest that CP has anti-obesity potential by inhibiting PL, thus helping to prevent the development of non-communicable diseases.

Gastrointestinal Digestion of Food Proteins under the Effects of Released Bioactive Peptides on Digestive Health.

The gastrointestinal tract represents a specialized interface between the organism and the external environment. Because of its direct contact with lumen substances, the modulation of digestive functions by dietary substances is supported by a growing body of evidence. Food-derived bioactive peptides have demonstrated a plethora of activities in the organism with increasing interest toward their impact over the digestive system and related physiological effects. This review updates the biological effects of food proteins, specifically milk and soybean proteins, associated to gastrointestinal health and highlights the study of digestion products and released peptides, the identification of the active form/s, and the evaluation of the mechanisms of action underlying their relationship with the digestive cells and receptors. The approach toward the modifications that food proteins and peptides undergo during gastrointestinal digestion and their bioavailability is a crucial step for current investigations on the field. The recent literature on the regulation of digestive functions by peptides has been mostly considered in terms of their influence on gastrointestinal motility and signaling, oxidative damage and inflammation, and malignant cellular proliferation. A final section regarding the actual challenges and future perspectives in this scientific topic is critically discussed.