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Abstract

Processing of whey proteins yields several bioactive peptides that can trigger physiological effects in the human body: on the nervous system via their opiate and ileum-contracting activities; on the cardiovascular system via their antithrombotic and antihypertensive activities; on the immune system via their antimicrobial and antiviral activities; and on the nutrition system via their digestibility and hypocholesterolemic effects. The specific physiological effects, as well the mechanisms by which they are achieved and the stabilities of the peptides obtained from various whey fractions during their gastrointestinal route, are specifically discussed in this review.
... These products, known as bioactive peptides, can also be released during fermentation and/or enzymatic processing of dairy products and ingredients due to hydrolysis of proteins [2]. Bioactive peptides derived from caseins (CN) and whey proteins (WP) have shown several biological functions, including anti-hypertensive, opioid, immune modulatory, antioxidant, antimicrobial and others [2][3][4][5]. Among the most studied bioactive peptides in human physiology are those associated with regulating the cardiovascular system [3,5,6], since arterial hypertension is the leading cause of death of more than 10 million people annually [7]. ...
... Bioactive peptides derived from caseins (CN) and whey proteins (WP) have shown several biological functions, including anti-hypertensive, opioid, immune modulatory, antioxidant, antimicrobial and others [2][3][4][5]. Among the most studied bioactive peptides in human physiology are those associated with regulating the cardiovascular system [3,5,6], since arterial hypertension is the leading cause of death of more than 10 million people annually [7]. In the human According to the pH conditions described by the experimental design (Table 1), 160 mL of whey protein solutions were distributed in 250 mL bottles (Nalgene 2625F68, Thomas Scientific, Swedesboro, NJ, USA) and placed in a water bath (Model LSB-030S, LabTech, Jakarta, Indonesia) under continuous agitation at 150 rpm for 10 min to equilibrate the temperature to the specific treatment conditions (i.e., papain, 60 • C; bromelain and ficin, 50 • C; Table 1). ...
... Whey protein hydrolysates were made under the conditions detailed inTable 3.3 From treatment before simulated gastrointestinal digestion.4 From treatment after simulated gastrointestinal digestion.5 "+" indicates that the peptide was present in the sample/treatment; "−" indicates that the peptide was not detected in the sample/treatment.6 ...
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Hydrolysis of proteins leads to the release of bioactive peptides with positive impact on human health. Peptides exhibiting antihypertensive properties (i.e., inhibition of angiotensin-I-converting enzyme) are commonly found in whey protein hydrolysates made with enzymes of animal, plant or microbial origin. However, bioactive properties can be influenced by processing conditions and gastrointestinal digestion. In this study, we evaluated the impact of three plant enzymes (papain, bromelain and ficin) in the manufacture of whey protein hydrolysates with varying level of pH, enzyme-to-substrate ratio and time of hydrolysis, based on a central composite design, to determine the degree of hydrolysis and antihypertensive properties. Hydrolysates made on laboratory scales showed great variation in the type of enzyme used, their concentrations and the pH level of hydrolysis. However, low degrees of hydrolysis in papain and bromelain treatments were associated with increased antihypertensive properties, when compared to ficin. Simulated gastrointestinal digestion performed for selected hydrolysates showed an increase in antihypertensive properties of hydrolysates made with papain and bromelain, which was probably caused by further release of peptides. Several peptides with reported antihypertensive properties were found in all treatments. These results suggest plant enzymes used in this study can be suitable candidates to develop ingredients with bioactive properties.
... Whey proteins and their hydrolysates are important emulsifiers in food emulsions [1][2][3][4] and are also sources of significant bioactive peptide molecules [5,6], which are beneficial for promoting good health in humans. Whey protein peptides have antioxidant, angiotensin-I-converting enzyme (ACE)-inhibition and anti-hypertensive [5,7], opiate [7], immunomodulatory [8], and antidiabetic [9] properties. ...
... Whey proteins and their hydrolysates are important emulsifiers in food emulsions [1][2][3][4] and are also sources of significant bioactive peptide molecules [5,6], which are beneficial for promoting good health in humans. Whey protein peptides have antioxidant, angiotensin-I-converting enzyme (ACE)-inhibition and anti-hypertensive [5,7], opiate [7], immunomodulatory [8], and antidiabetic [9] properties. These peptides are considered safe and healthy compounds [7], easily absorbed by the human body, and used as functional and nutraceutical agents. ...
... Whey protein peptides can inhibit the activity of ACE [5]. To complement the antioxidant activity, WPI peptides were screened for their ACE-inhibition activity. ...
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Whey protein isolate (WPI)-derived bioactive peptide fractions (1–3, 3–5, 5–10, 1–10, and >10 kDa) were for the first time used as emulsifiers in nanoemulsions. The formation and storage stability of WPI bioactive peptide-stabilized nanoemulsions depended on the peptide size, enzyme type, peptide concentration, and storage temperature. The highly bioactive <10 kDa fractions were either poorly surface-active or weak stabilizers in nanoemulsions. The moderately bioactive >10 kDa fractions formed stable nanoemulsions (diameter = 174–196 nm); however, their performance was dependent on the peptide concentration (1–4%) and enzyme type. Overall, nanoemulsions exhibited better storage stability (less droplet growth and creaming) when stored at lower (4 °C) than at higher (25 °C) temperatures. This study has shown that by optimizing peptide size using ultrafiltration, enzyme type and emulsification conditions (emulsifier concentration and storage conditions), stable nanoemulsions can be produced using WPI-derived bioactive peptides, demonstrating the dual-functionality of WPI peptides.
... These proteins have a globular structure with high solubility and are easily denatured by heat (Lievore et al. 2015), they have the ability to form intramolecular bonds through disulfide between sulfhydryl groups present in cysteine . In addition to their nutritional value, due to their high content of essential amino acids, whey proteins perform various biological functions, which is why they represent an interest factor in various food applications (Madureira et al. 2010;Mollea, Marmo, and Bosco 2013). ...
... Although the nutritional and functional properties of whey proteins have been reported (A. R. Madureira et al. 2010;Dullius, Goettert, and de Souza 2018), it is known that many of the compounds that exert the beneficial effects are found encrypted in the amino acid chain of proteins and are only released through their hydrolysis (Pihlanto-Leppälä 2000). The released compounds are called bioactive peptides, (Dullius, Goettert, and de Souza 2018) and these fractions are obtained through the action of digestive enzymes, as well as by the action of microbial proteases, including the contained in lactic acid bacteria (LAB) (Korhonen 2009;Corrêa et al. 2014;Xia et al. 2020). ...
... The former is used for the generation of short peptides, while the latter is common to synthesize peptides composed by 10 to 100 residues. However, its application to produce peptides at an industrial level is unfeasible (Madureira et al. 2010). ...
Article
Bioactive peptides derived from diverse food proteins have been part of diverse investigations. Whey is a rich source of proteins and components related to biological activity. It is known that proteins have effects that promote health benefits. Peptides derived from whey proteins are currently widely studied. These bioactive peptides are amino acid sequences that are encrypted within the first structure of proteins, which required hydrolysis for their release. The hydrolysis could be through in vitro or in vivo enzymatic digestion and using microorganisms in fermented systems. The biological activities associated with bio-peptides include immunomodulatory properties, antibacterial, antihypertensive, antioxidant and opioid, etc. These functions are related to general conditions of health or reduced risk of certain chronic illnesses. To determine the suitability of these peptides/ingredients for applications in food technology, clinical studies are required to evaluate their bioavailability, health claims, and safety of them. This review aimed to describe the biological importance of whey proteins according to the incidence in human health, their role as bioactive peptides source, describing methods, and obtaining technics. In addition, the paper exposes biochemical mechanisms during the activity exerted by biopeptides of whey, and their application trends.
... A high ACE inhibition index has been estimated for the tryptic hydrolysates of cow α-LA, β-LG, and WPC80 [45]. ACE-IA is related to the existence of hydrophobic amino acid residues at the C-terminal end and a molecular mass less than 3000; further degradation of tryptic peptides may strengthen or reduce their ACE-inhibitory potential [5,45]. ...
... A high ACE inhibition index has been estimated for the tryptic hydrolysates of cow α-LA, β-LG, and WPC80 [45]. ACE-IA is related to the existence of hydrophobic amino acid residues at the C-terminal end and a molecular mass less than 3000; further degradation of tryptic peptides may strengthen or reduce their ACE-inhibitory potential [5,45]. The most common features of ACE inhibiting antihypertensive peptides derived from β-LG and α-LA, i.e., lactokinins, have been concisely reviewed [7]. ...
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Tryptic WPHs with considerable residual whey protein content intact were developed from two sheep/goat WPCs (65% and 80% protein) without pH control. Pasteurization was used to avoid denaturation. Changes in non-protein nitrogen (DH_TCASN), free amino groups (DH_TNBS), and major whey proteins were used to investigate the degree and extent of hydrolysis. Antihypertensive potential (ACE-IA), radical scavenging (DPPH-RSA), and iron chelation (Fe-CA) were assessed. No statistically significant changes in pH (5.84–6.29) were observed during hydrolysis and storage. At the start of hydrolysis, DH_TCASN was ≅11% for both substrates whereas DH_TNBS was >10% and >5% for WP65 and WP80, respectively. After one-hour hydrolysis, DH_TCASN was ≅17% for both substrates and DH_TNBS was ≅15% and ≅11% for WP65 and WP80, respectively. The β-lactoglobulin, α-lactalbumin, and caseinomacropeptide of WP65 were hydrolyzed by 14 ± 1.3%, 73.9 ± 2.6% and 37 ± 2.6%. The respective values for WP80 were 14.9 ± 1.7%, 79.9 ± 1%, and 32.7 ± 4.8%. ACE-IA of the hydrolysates of both substrates was much higher (>80%) than that of controls (<10%). Hydrolysis, substrate type, and storage did not affect the DPPH-RSA (45–54%). Fe-CA of the WP65 and WP80 hydrolysates were ≅40% and ≅20%, respectively; a similar outcome was found in the respective controls. Refrigerated storage for 17 h did not affect the degree of hydrolysis and biofunctional activities.
... In fact, α-LA is a key agent in improving bacterial growth, gut microbiota and immunomodulation. By promoting the growth of several Bifidobacterium strains [11], these bioactive peptides from α-LA may further prevent infections related to pathogens like Escherichia coli, Salmonella typhimurium, Staphylococcus aureus and Klebsiella pneumonia [12], thus improving the chronic condition of altered microbiota. ...
Article
To date, the involvement of α-Lactalbumin (α-LA) in the management of polycystic ovary syndrome (PCOS) refers to its ability to improve intestinal absorption of natural molecules like inositols, overcoming the inositol resistance. However, due to its own aminoacidic building blocks, α-LA is involved in various biological processes that can open new additional applications. A great portion of women with PCOS exhibit gastrointestinal dysbiosis, which is in turn one of the triggering mechanisms of the syndrome. Due to its prebiotic effect, α-LA can recover dysbiosis, also improving the insulin resistance, obesity and intestinal inflammation frequently associated with PCOS. Further observations suggest that altered gut microbiota negatively influence mental wellbeing. Depressive mood and low serotonin levels are indeed common features of women with PCOS. Thanks to its content of tryptophan, which is the precursor of serotonin, and considering the strict link between gut and brain, using α-LA contributes to preserving mental well-being by maintaining high levels of serotonin. In addition, considering women with PCOS seeking pregnancy, both altered microbiota and serotonin levels can induce later consequences in the offspring. Therefore, a deeper knowledge of potential applications of α-LA is required to transition to preclinical and clinical studies extending its therapeutic advantages in PCOS.
... All proteases have a certain degree of specificity in their substrate, generally based on a sequence of amino acids directly surrounding the bond that is cleaved (115). An extensive variety of bioactive hydrolysates and peptides have been produced from peanut, corn, soy, whey, and other protein sources (116)(117)(118)(119). A conventional approach is mostly used to produce and identify the bioactive peptides (Figure 4). ...
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Oats are considered the healthiest grain due to their high content of phytochemicals, dietary fibers, and protein. In recent years, oat protein and peptides have gained popularity as possible therapeutic or nutraceutical candidates. Generally, oat peptides with bioactive properties can be obtained by the enzymatic hydrolysis of proteins and are known to have a variety of regulatory functions. This review article focused on the nutraceutical worth of oat proteins and peptides and also describes the application of oat protein as a functional ingredient. Outcomes of this study indicated that oat protein and peptides present various therapeutical properties, including antidiabetic, antioxidant, antihypoxic, antihypertensive, antithrombotic, antifatigue, immunomodulatory, and hypocholestrolaemic. However, most of the conducted studies are limited to in vitro conditions and less data is available on assessing the effectiveness of the oat peptides in vivo. Future efforts should be directed at performing systematic animal studies; in addition, clinical trials also need to be conducted to fully support the development of functional food products, nutraceutical, and therapeutical applications.
Article
There are limited naturally derived protein biomaterials for the available medical implants. High cost, low yield, and batch-to-batch inconsistency, as well as intrinsically differing bioactivity in some of the proteins, make them less beneficial as common implant materials compared to their synthetic counterparts. Here, we present a milk-derived whey protein isolate (WPI) as a new kind of natural protein-based biomaterial for medical implants. The WPI was methacrylated at 100 g bench scale, >95% conversion, and 90% yield to generate a photo-cross-linkable material. WPI-MA was further processed into injectable hydrogels, monodispersed microspheres, and patterned scaffolds with photo-cross-linking-based advanced processing methods including microfluidics and 3D printing. In vivo evaluation of the WPI-MA hydrogels showed promising biocompatibility and degradability. Intramyocardial implantation of injectable WPI-MA hydrogels in a model of myocardial infarction attenuated the pathological changes in the left ventricle. Our results indicate a possible therapeutic value of WPI-based biomaterials and give rise to a potential collaboration between the dairy industry and the production of medical therapeutics.
Chapter
The need for more sustainable production processes has led to the evolution of the so-called biorefineries. The search for inexpensive feedstocks that do not compete with food supplies has been of constant great interest since biorefineries’ viability largely depends on this. An abundant, residual, and non-seasonal type of material is whey, which is derived from cheese production. The conversion of the high lactose content present in the whey can be potentially used both, in the generation of biofuels, and in obtaining value-added products, in a biorefinery approach. The chapter presents a review of essential biorefineries concepts and whey use in biofuels and aroma production. Furthermore, the conceptual flowsheet of a whey biorefinery is presented, which involves the production of aromas such as 2-phenylethanol (2-PEA) and isoamyl acetate (IA); simultaneously with bioethanol (bioET) generation. Whey biorefinery presents an area of opportunity to achieve a more sustainable bioproducts production.
Article
Requeson cheese is obtained from whey proteins. The production of this cheese is the most economical way to recover and concentrate whey proteins, which is why it is frequently made in some Latin American countries. Four requeson cheese treatments were prepared with different concentrations and combinations of salts (sodium chloride and/or potassium chloride) and were conventionally or vacuum packed. Proteolysis, peptide concentration, angiotensin-converting enzyme (ACE) inhibitory and antioxidant (DPPH and ABTS) activities were evaluated over time (one, seven and fourteen days). Requeson cheese presented antioxidant and ACE inhibitory activities, however, these values vary depending on salt addition, type of packaging and time of storage. The highest values of antioxidant activity (ABTS) were found in cheese added with 1.5% NaCl and 1.5% (NaCl/KCl, 1:1). Cheese without added salt and vacuum packed presented the highest ACE inhibition percentage at day seven. Therefore, it can be concluded that requeson cheese elaborated exclusively of sweet whey, presents antioxidant and ACE inhibition activity. However, for a cheese with ACE inhibitory capacity, it is recommended not to add salts or add at 1% (NaCl) and vacuum pack it. Additionally, for a cheese with antioxidant activity, it is recommended to add salt at 1.5% either NaCl or (1:1) NaCl/KCl and pack it either in a polyethylene bag or vacuum. In conclusion, requeson cheese elaborate with 100% sweet whey is a dairy product with antioxidant and ACE inhibition activity, being low in salt and fat.
Chapter
In this chapter, the authors explore the physicochemical composition of whey from bovine milk, the most representative technologies used for the production of added‐value products and bioactive compounds or biomolecules from industrialization of whey such as whey protein fractions, peptides, and oligosaccharides, beneficial properties and food applications of these products. In addition, the use of whey as the encapsulating material of bioactive compound‐loaded liposomes, and the presence of bacteriophages in whey derived products, are also discussed. Whey derived products enriched in proteins are widely used in many food and pharmaceutical applications because of their broad range of functionality, nutritive value, and health benefits. In addition, the demand for whey proteins has been boosted by the consumer request for high‐protein foods and supplements. The authors also focus on the structure, characteristics, technology of production, biological properties, and applications of some peptides such as antihypertensive, antimicrobial and antioxidant, GMP, GOS and lactosucrose.
Article
The cytokine and cell attachment protein osteopontin (OPN) is not necessary for the development and survival of mice in a clean animal facility. The primary role of OPN appears to be that of facilitating recovery of the organism after injury or infection, which generally causes an increase in its expression. It also is essential for some forms of bone remodeling. OPN stimulates cellular signaling pathways via various receptors found on most cell types and can encourage cell migration. OPN modulates immune and inflammatory responses and possibly negatively regulates Ras signaling pathways. Its apparent ability to enhance cell survival by inhibiting apoptosis may explain why the metastatic proficiency of tumor cells increases with increased OPN expression. J. Cell. Biochem. Suppls. 30/31:92–102, 1998. © 1998 Wiley‐Liss, Inc.
Article
The cytokine and cell attachment protein osteopontin (OPN) is not necessary for the development and survival of mice in a clean animal facility. The primary role of OPN appears to be that of facilitating recovery of the organism after injury or infection, which generally causes an increase in its expression. It also is essential for some forms of bone remodeling. OPN stimulates cellular signaling pathways via various receptors found on most cell types and can encourage cell migration. OPN modulates immune and inflammatory responses and possibly negatively regulates Ras signaling pathways. Its apparent ability to enhance cell survival by inhibiting apoptosis may explain why the metastatic proficiency of tumor cells increases with increased OPN expression. J. Cell. Biochem. Suppls. 30/31:92-102, 1998. © 1998 Wiley-Liss, Inc.