Food-derived Bioactive Peptides Research Articles

Interplay of Food-Derived Bioactive Peptides with Gut Microbiota: Implications for Health and Disease Management.

Bioactive peptides (BPs) are protein fragments with beneficial effects on metabolism, physiology, and diseases. This review focuses on proteolytic BPs, which are produced by the action of gut microbiota on proteins in food and have demonstrated to influence the composition of gut microbes. And gut microbiota are candidate targets of BPs to alleviate oxidative stress, enhance immunity, and control diseases, including diabetes, hypertension, obesity, cancer, and immune and neurodegenerative diseases. Despite promising results, further research is needed to understand the mechanisms underlying the interactions between BPs and gut microbes, and to identify and screen more BPs for industrial applications. Overall, BPs offer potential as therapeutic agents for various diseases through their interactions with gut microbes, highlighting the importance of continued research in this area.

Potential Impact of Bioactive Peptides from Foods in the Treatment of Hypertension.

High blood pressure (BP) is the main preventable risk factor for cardiovascular diseases (CVDs). Much research is aimed at finding natural alternatives to control or prevent hypertension (HT), since some hypertensive patients do not respond to current pharmacological treatments or show undesirable side effects. Forty relevant articles have been selected from various scientific literature databases. The results reveal that angiotensin-converting enzyme (ACE) inhibition is the most reported mechanism of action of antihypertensive peptides. The active peptides have a great variety of origins. Biopeptides with a molecular weight of <3 kDa, short chain <20 amino acids, and a hydrophobic amino acid sequence at the C- and N-terminus exhibit higher antihypertensive activity. They also show good stability to enzymatic hydrolysis and gastrointestinal digestion, and no toxicity. To determine antihypertensive effectiveness, in vitro and in vivo animal studies are the most frequent developed, with few in silico studies and only one human clinical trial. There is interesting potential for antihypertensive peptides as promising natural candidates for the development of functional foods, nutraceuticals and drugs for preventive or therapeutic treatment of hypertension. The aim of this review is to study the role of food-derived bioactive peptides in HT.

Bioactive peptides as alternative treatment for Helicobacter pylori infection

The infection and chronic inflammatory response generated by Helicobacter pylori is a global health concern. This pathogen is characterized as a major risk factor in the development of gastric cancer and other diseases. Conventional eradication therapies are based on antibiotic regimens and as a consequence there is an increase in antimicrobial resistance of the pathogen strains, besides other potential side effects for the host. Therefore, it is necessary to explore new alternatives. This review delves into the realm of antimicrobial peptides, exploring their efficacy against H. pylori sourced from diverse origins. Furthermore, it sheds light on food-derived peptides exhibiting remarkable biological activity. These peptides exhibit promising effects on biomarkers associated with H. pylori infection, demonstrating anti-inflammatory and antioxidant properties validated through rigorous testing in both cell and animal models. Regarding the anti-inflammatory activity, the peptide VPY derived from soybean and the peptides derived from animal sources such as meat (β-Ala-His), egg (DEDTQAMPFR, DEDTQAMPF, MLGATSL, MSYSAGF, CR, FL, HC, LL, MK) and milk (IPAV) have reported a reduction of the cytokine IL-8, biomarker directly related to H. infection. For the antioxidant activity, peptides derived from milk (EAMAPK, AVPYPQ) and from Spirulina maxima (LDAVNR, MMLDF) have reduced ROS levels and could have a positive effect on the control of H. infection. Food-derived bioactive peptides with an anti-adhesive effect were also discussed. They derive from vegetable sources (corn, pea and wheat) and are capable of interacting with the host cells, interfering the adherence of H. pylori. Food-derived bioactive peptides have potential to avoid and/or mitigate undesired outcomes of infectious diseases due to the possibility of its application in nutraceuticals and food products, resulting in a preventive approach. Keywords: Helicobacter pylori, antibiotic resistance, bioactive peptides, antimicrobial peptides

Food-derived bioactive peptides with anti-hyperuricemic activity: A comprehensive review

Hyperuricemia (HU) is a metabolic disorder caused by the overproduction or underexcretion of uric acid (UA) in the human body. Several approved drugs for the treatment of HU are available in the market; however, all these allopathic drugs exhibit multiple side effects. Therefore, the development of safe and effective anti-HU drugs is an urgent need. Natural compounds derived from foods and plants have the potential to decrease UA levels. Recently, food-derived bioactive peptides (FBPs) have gained attention as a functional ingredient owing to their biological activities. In the current review, we aim to explore the urate-lowering potential and the underlying mechanisms of FBPs. We found that FBPs mitigate HU by reducing blood UA levels through inhibiting key enzymes such as xanthine oxidase, increasing renal UA excretion, inhibiting renal UA reabsorption, increasing anti-oxidant activities, regulating inflammatory mediators, and addressing gut microbiota dysbiosis. In conclusion, FBPs exhibit strong potential to ameliorate HU.

Recent progress of food‐derived bioactive peptides: Extraction, purification, function, and encapsulation

AbstractFunctional peptides constitute a class of small molecular peptide chains with specific functions in biology and are typically composed of various amino acids. The chemical‐synthesis methods for preparation of functional peptides can bring high toxicity to the human body. Therefore, there is a growing need to explore alternative, safter sources to obtain bioactive peptides. Food‐derived bioactive peptides (FBPs) stand out as an ideal substitution offering safety and accessibility that can be used in health products and pharmaceuticals to elicit their effects. Presently, the extraction, purification, functional properties, and bioavailability of FBPs have been poorly summarized. This review aims to address this gap by summarizing key aspects of FBPs, covering their source, methods of preparation, extraction, isolation, purification, and identification. Additionally, the review explores the functional characteristics and mechanism underlying FBPs. Emphasis is placed on strategies to enhance the stability and bioaccessibility of FBPs, crucial for their successful application in the food and medical industries. Existing research findings suggest that adopting appropriate methods can extract FBPs with high yield and purity. FBPs exhibit both in vitro and in vivo biological activities regulating relevant pathways, showcasing their potential in the medical field. In the quest for improved stability, the application of nanomaterials emerges as a promising strategy. These advancements collectively hint at a bright future for FBPs in both food and medical matrices. As the field progresses, further exploration and refinement of extraction techniques, functional properties, and bioavailability will contribute to unlocking the full potential of FBPs in various applications.

Preparation, Biological Activities, and Potential Applications of Hen Egg-Derived Peptides: A Review.

Food-derived peptides have been extensively studied for their benefits in humans. Hen eggs, characterized by high protein and digestibility, are an excellent source of food-derived bioactive peptides. This review summarizes the preparation methods, purification, and identification of hen egg-derived peptides (HEPs). The preparation methods mainly include enzymatic hydrolysis, microbial fermentation, and chemical synthesis. Genetic engineering is an emerging trend of HEP preparation. Then, we summarize the biological activities of HEPs, such as antioxidant activities, enzyme inhibitory activity, and antibacterial activity, of which the enzyme inhibitory activity is comprehensively summarized for the first time. The structure-activity relationship and underlying mechanism of the HEPs are further elucidated. Finally, the applications, future challenges, and opportunities of HEPs were mainly discussed in the food and non-food sectors. We focus on the potential applications of HEPs in intestinal health and assembly delivery and provide a reference for the further utilization and commercial development of HEPs.

IRW improves diet-induced non-alcoholic fatty liver disease by reducing steatosis associated with increased capacity for oxidative phosphorylation

Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, remains without approved pharmacological treatment. Food-derived bioactive peptides can aid in the management of metabolic conditions including hypertension, obesity and insulin resistance. IRW (isoleucine-arginine-tryptophan) is a tripeptide produced from egg white with angiotensin converting enzyme-inhibitory properties. IRW supplementation elicits antihypertensive effects, improves skeletal muscle insulin signaling and glucose tolerance while reducing body weight gain. In this study, we hypothesized that IRW supplementation would prevent high-fat diet (HFD)-induced NAFLD by modulating hepatic lipid metabolism and increasing mitochondrial content. We found that IRW prevents diet-induced NAFLD, while rosiglitazone (ROSI) treatment worsens it. IRW decreases hepatic triglyceride content and lipid droplet size compared to HFD and ROSI. IRW increases the hepatic mitochondrial complexes and citrate synthase activity, phosphorylation of 5'-AMP-activated protein kinase and microsomal triglyceride transfer protein abundance compared to HFD. Compared with ROSI, IRW increases phosphorylated acetyl CoA carboxylase and mitochondrial complexes. Overall, the hypothesis is supported by these findings.

Comprehensive review on some food-derived bioactive peptides with anti-hypertension therapeutic potential for angiotensin-converting enzyme (ACE) inhibition

Comprehensive review on some food-derived bioactive peptides with anti-hypertension therapeutic potential for angiotensin-converting enzyme (ACE) inhibition

Production of Food-Derived Bioactive Peptides with Potential Application in the Management of Diabetes and Obesity: A Review.

The prevalence of diabetes mellitus and obesity is increasing worldwide. Bioactive peptides are naturally present in foods or in food-derived proteins. Recent research has shown that these bioactive peptides have an array of possible health benefits in the management of diabetes and obesity. First, this review will summarize the top-down and bottom-up production methods of the bioactive peptides from different protein sources. Second, the digestibility, bioavailability, and metabolic fate of the bioactive peptides are discussed. Last, the present review will discuss and explore the mechanisms by which these bioactive peptides help against obesity and diabetes based on in vitro and in vivo studies. Although several clinical studies have demonstrated that bioactive peptides are beneficial in alleviating diabetes and obesity, more double-blind randomized controlled trials are needed in the future. This review has provided novel insights into the potential of food-derived bioactive peptides as functional foods or nutraceuticals to manage obesity and diabetes.

Potential of Food Protein-Derived Bioactive Peptides against Sarcopenia: A Comprehensive Review.

Sarcopenia is an age-related progressive muscle disorder characterized by accelerated loss of muscle mass, strength, and function, which are important causes of physiological dysfunctions in the elderly. At present, the main alleviating method includes protein supplements to stimulate synthesis of muscle proteins. Food protein-derived peptides containing abundant branched-chain amino acids have a remarkable effect on the improvement of sarcopenia. Understanding the underlying molecular mechanism and clarifying the structure-activity relationship is essential for the mitigation of sarcopenia. This present review recaps the epidemiology, pathogenesis, diagnosis, and treatment of sarcopenia, which facilitates a comprehensive understanding of sarcopenia. Moreover, the latest research progress on food-derived antisarcopenic peptides is reviewed, including their antisarcopenic activity, molecular mechanism as well as structural characteristics. Food-derived bioactive peptides can indeed alleviate/mitigate sarcopenia. These antisarcopenic peptides play a pivotal role mainly by activating the PI3K/Akt/mTOR and MAPK pathways and inhibiting the ubiquitin-proteasome system and AMPK pathway, thus promoting the synthesis of muscle proteins and inhibiting their degradation. Antisarcopenic peptides alleviate sarcopenia via specific peptides, which may be absorbed into the circulation and exhibit their bioactivity in intact forms. The present review provides a theoretical reference for mitigation and prevention of sarcopenia by food protein-derived bioactive peptides.

Walnut-derived peptide PPKNW alleviate polystyrene microparticles-induced growth inhibition of Lactobacillus rhamnosus GG

Microplastic (MP) is ubiquitous and makes human exposure inevitable through the consumption of food. The impact of MP on the gut microbiome and human health is still unclear. Here, we investigated the ability of food derived peptides to counteract the inhibitory effect of polystyrene microplastic (PS-MP) on probiotics and elucidated the underlying mechanism. Pro-Pro-Asn-Lys-Trp (PW5,100 μg/mL), derived from walnut-protein, significantly reversed the growth inhibition of Lactobacillus rhamnosus by PS500 (Area under the curve increased by 13.74%, p < 0.01). Furthermore, the effectiveness of orally administered PW5 was explored by NMR, our results suggest that the intact peptide is necessary for the observed activity of PW5.PW5 and PS500 primarily interact through hydrogen bonding and van der Waals forces to form new complexes. Together, our data demonstrated the potential mechanism by which food-derived peptides bind to PS-MP to reduce the inhibitory effect of MP on probiotic growth, and opens a new perspective for the application of food-derived bioactive peptides in reducing the growing health risks posed by MP.

Food-derived Bioactive Peptides with Angiotensin-Converting Enzyme Inhibiting Effect: A Systematic Review

Objective To describe the current scientific evidence of food-derived bioactive peptides and their angiotensin-converting enzyme inhibiting effect. Methods Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed. We searched MEDLINE (through PubMed) and Science Direct databases to identify studies assessing food-derived bioactive peptides and angiotensin-converting enzyme-inhibiting effects. The evidence was organized and presented using tables and narrative synthesis. Results We identified 11 peptides with the best antihypertensive potential: RDGGYCC, LRLESF, FHAPWK, and LVLPG from plants; LSGYGP, ITT, VISDEDGVTH, ATT, and LWHTH from animals; and ALGRV and SPQW from fungi, which demonstrated their antihypertensive potential in vitro and in vivo. Conclusion Overall, food-derived bioactive peptides with hypertensive activity were identified, which shows a promising field as a therapeutic alternative to conventional pharmacological treatments.

Evaluation of Anti-Oxinflammatory and ACE-Inhibitory Properties of Protein Hydrolysates Obtained from Edible Non-Mulberry Silkworm Pupae (Antheraea assama and Philosomia ricinii).

Food-derived bioactive peptides (BAPs) obtained from edible insect-protein hold multiple activities promising the potential to target complex pathological mechanisms responsible for chronic health conditions such as hypertension development. In this study, enzymatic protein hydrolysates from non-mulberry edible silkworm Antheraea assama (Muga) and Philosomia ricini (Eri) pupae, specifically Alcalase (A. assama) and Papain (P. ricini) hydrolysates obtained after 60 and 240 min, exhibited the highest ACE-inhibitory and antioxidant properties. The hydrolysates' fractions (<3, 3-10 and >10 kDa), specifically Alc_M60min_F3 (≤3 kDa) and Pap_E240min_F3 (≤3 kDa), showed the highest antioxidant and ACE-inhibitory activities, respectively. Further RP-HPLC purified sub-fractions F4 and F6 showed the highest ACE inhibition as well as potent anti-oxinflammatory activities in lipopolysaccharide (LPS)-treated endothelial cells. Indeed, F4 and F6 ACE-inhibitory peptide fractions were effective in preventing p65 nuclear translocation after 3 h of LPS stimulation along with the inhibition of p38 MAPK phosphorylation in HUVEC cells. In addition, pretreatment with F4 and F6 ACE-inhibitory peptide fractions significantly prevented the LPS-induced upregulation of COX-2 expression and IL-1β secretion, while the expression of NRF2 (nuclear factor erythroid 2-related factor 2)-regulated enzymes such as HO-1 and NQO1 was induced by both peptide fractions. The derived peptides from edible pupae protein hydrolysates have potentialities to be explored as nutritional approaches against hypertension and related cardiovascular diseases.

Effects of the dipeptides comprising leucine and lysine on lifespan and age-related stress in Caenorhabditis elegans.

The aging process is affected by various stressors. An increase in oxidative stress is related to the impairment of physiological functions and enhancement of glycative stress. Food-derived bioactive peptides have various physiological functions, including antioxidant activities. Dipeptides comprising Leu and Lys (LK and KL, respectively) have been isolated from foods; however, their physiological properties remain unclear. In this study, we investigated the antioxidant/antiglycation activity of dipeptides and their antiaging effects using Caenorhabditis elegans (C.elegans). Both dipeptides showed antioxidant activities against several reactive oxygen species (ROS) in vitro. In particular, the scavenging activity of LK against superoxide radicals was higher than KL did. Moreover, dipeptides suppressed advanced glycation end products (AGEs) formation in the BSA-glucose model. In the lifespan assays using wild-type C.elegans, both LK and KL significantly prolonged the mean lifespan by 20.9% and 11.7%, respectively. In addition, LK decreased intracellular ROS and superoxide radical levels in C.elegans. Blue autofluorescence, an indicator of glycation in C.elegans with age, was also suppressed by LK. These results suggest that dipeptides, notably LK, show an antiaging effect by suppressing oxidative and glycative stress. Our findings suggest that such dipeptides can be used as a novel functional food ingredient. Food-derived dipeptide Leu-Lys (LK) and Lys-Leu (KL) exert antioxidant and antiglycation activity in vitro. Treatment with LK prolonged the mean lifespan and maximum lifespan of C.elegans more than that of KL. Intracellular ROS and blue autofluorescence levels (indicator of aging) were suppressed by LK.

Mechanism of Molecular Activity of Yolkin—a Polypeptide Complex Derived from Hen Egg Yolk—in PC12 Cells and Immortalized Hippocampal Precursor Cells H19-7

Food-derived bioactive peptides able to regulate neuronal function have been intensively searched and studied for their potential therapeutic application. Our previous study showed that a polypeptide complex yolkin, isolated from hen egg yolk as a fraction accompanying immunoglobulin Y (IgY), improved memory and cognitive functions in rats. However, the mechanism activated by the yolkin is not explained. The goal of the present study was to examine what molecular mechanism regulating brain-derived neurotrophic factor (BDNF) expression is activated by the yolkin complex, using in vitro models of PC12 cell line and fetal rat hippocampal cell line H19-7. It was shown that yolkin increased the proliferative activity of rat hippocampal precursor cells H19-7 cells and upregulated the expression/production of BDNF in a cyclic adenosine monophosphate (cAMP)-response element-binding protein (CREB)-dependent manner. Additionally the upregulation of carboxypeptidase E/neurotrophic factor–α1 (CPE/(NF-α1) expression was shown. It was also determined that upregulation of CREB phosphorylation by yolkin is dependent on cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) and phosphoinositide 3-kinases/protein kinase B (PI3K/Akt) signaling pathway activation. Moreover, the impact of yolkin on the level of intracellular Ca2+, nitric oxide, and activation of extracellular signal-regulated kinases 1/2 (ERK 1/2 kinase) was excluded. These results emphasize that yolkin can act comprehensively and in many directions and may participate in the regulation of neurons’ survival and activity. Therefore, it seems that the yolkin specimen can be used in the future as a safe, bioavailable, natural nutraceutical helping to improve the cognition of older people.

Preparation and characterization of duck liver-derived antioxidant peptides based on LC-MS/MS, molecular docking, and machine learning

In this study, 4 novel duck liver-derived bioactive peptides with high antioxidant capacity were prepared by fermentation, RP-HPLC purification, LC-MS/MS identification, molecular docking, and machine learning. The molecular docking results demonstrated their antioxidant power mainly by forming hydrogen bonds between their amino acid residues and free radical molecules. Machine learning further confirmed their ACE inhibitory and antioxidant effects. Moreover, in H2O2-induced HepG2 oxidative damage cell models, they could increase the activities and mRNA expression levels of intracellular antioxidant enzymes (SOD, CAT, and GSH-Px), and reduce the content of malondialdehyde (MDA) and reactive oxygen species (ROS) accumulation, thereby inhibiting intracellular oxidative damage. It has important implications for the high-value utilization of duck liver byproducts and food-derived bioactive peptides drinks development.

PepLab Platform: Database and Software Tools for Analysis of Food-Derived Bioactive Peptides

Research on food-derived bioactive peptides is expanding and the need for a convenient online platform that combines a foolproof and intuitive user interface with a reliable database and tools for prediction and analysis is rising. In this regard, this paper presents an open-access web-based platform PepLab (Peptides Laboratory). The database contains 2764 peptide sequence entries, grouped into sixteen classes according to their biological activity and into seven classes according to the source from which they were derived. Moreover, it includes bioinformatic tools for their processing and analysis. The DMpep tool allows extracting information about a number of physicochemical characteristics of a peptide or a set of peptides, including those that are not recorded in the database. The main advantages of PepLab are a user-friendly interface, a responsive design, and optimized search engines for better visibility on the Internet. Prediction of non-reported activity is available based on amino acid sequence analysis. In addition, users can download data and results in a convenient format (text and/or graphic) that was limited in the existing platforms. In this way, the presented PepLab platform will be helpful for researchers from various fields—bioinformatics, pharmaceuticals, food sciences, dietetics, biotechnology, analytical chemistry, etc.

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.

Insight into the self-assembly and gel formation of a bioactive peptide derived from bovine casein

The self-assembling and gelation properties of a bioactive peptide derived from bovine casein (FFVAPFPEVFGK) were studied in the peptide's natural form (uncapped, uncapFFV) and capped with protecting groups added to both termini (capped, capFFV). Although the natural peptide (uncapFFV) did not demonstrate self-assembly, the capped peptide (capFFV) spontaneously self-assembled and formed a self-supporting gel. Variations in peptide concentration and incubation time influenced the gel's mechanical properties, suggesting the peptide's properties could be tuned and exploited for different applications. These results suggest that food-derived bioactive peptides have good potential for self-assembly and therefore utilisation as gels in functional foods and nutraceuticals. Self-assembly is a natural phenomenon that occurs in many fundamental biological processes. Some peptides can self-assemble and form gels with tunable properties under given conditions. These properties, along with peptide bioactivity, can be combined to make unique biomaterials. Instead of synthesising the self-assembling bioactive peptides, we aim to extract them from natural sources. In order to use these peptides for different applications, it is essential to understand how we can trigger self-assembly and optimise the assembly conditions of these peptide gels. The self-assembling and gelation properties of a bioactive peptide derived from bovine casein (FFVAPFPEVFGK) were studied in the peptide's natural form (uncapped, uncapFFV) and capped with protecting groups added to both termini (capped, capFFV). Although the natural peptide (uncapFFV) did not demonstrate self-assembly, the capped peptide (capFFV) spontaneously self-assembled and formed a self-supporting gel. Variations in peptide concentration and incubation time influenced the gel's mechanical properties, suggesting the peptide's properties could be tuned and exploited for different applications. These results suggest that food-derived bioactive peptides have good potential for self-assembly and therefore utilisation as gels in functional foods and nutraceuticals.

Structure Characterization and Antihypertensive Effect of an Antioxidant Peptide Purified from Alcalase Hydrolysate of Velvet Antler.

Recently, interest in food-derived bioactive peptides as promising ingredients for the prevention and improvement of hypertension is increasing. The purpose of this study was to determine the structure and antihypertensive effect of an antioxidant peptide purified from velvet antler in a previous study and evaluate its potential as a various bioactive peptide. Molecular weight (MW) and amino acid sequences of the purified peptide were determined by quadrupole time-of-flight electrospray ionization mass spectroscopy. The angiotensin I-converting enzyme (ACE) inhibition activity of the purified peptide was assessed by enzyme reaction methods and in silico molecular docking analysis to determine the interaction between the purified peptide and ACE. Also, antihypertensive effect of the purified peptide in spontaneously hypertensive rats (SHRs) was investigated. The purified antioxidant peptide was identified to be a pentapeptide Asp-Asn-Arg-Tyr-Tyr with a MW of 730.31 Da. This pentapeptide showed potent inhibition activity against ACE (IC50 value, 3.72 μM). Molecular docking studies revealed a good and stable binding affinity between purified peptide and ACE and indicated that the purified peptide could interact with HOH2570, ARG522, ARG124, GLU143, HIS387, TRP357, and GLU403 residues of ACE. Furthermore, oral administration of the pentapeptide significantly reduced blood pressure in SHRs. The pentapeptide derived from enzymatic hydrolysate of velvet antler is an excellent ACE inhibitor. It might be effectively applied as an animal-based functional food ingredient.