Functional Significance of Bioactive Peptides Derived from Milk Proteins

Bioactive peptides can be defined as protein fragments with potential biological activities. Milk proteins are precursors of many different biologically active peptides. Bioactive peptides from milk proteins are considered potential modulators of various regulatory processes in the body. They mediate physiological functions in cardiovascular, nervous, gastro intestinal and immune systems. The functional significance of bioactivities depends on peptide fragment. Bioactive peptides encrypted in major milk proteins are latent within the sequence of the parent protein molecule. They can be liberated by (i) gastro intestinal digestion of milk, (ii) fermentation of milk with proteolytic starter cultures, and (iii) hydrolysis by proteolytic enzymes. In relation to their mode of action, bioactive peptides may reach target sites at the luminal side of intestinal tract, or after absorption, in peripheral organs. The production, functionalities, and mode of action of bioactive milk peptides as well as latest peptide products and ingredients are reviewed.     

Milk Derived Antimicrobial Bioactive Peptides: A Review

In recent decades, bioactive peptides have attracted increasing interest as health promoting functional foods. A variety of naturally formed bioactive peptides have been found in fermented dairy products such as yogurt, sour milk, and cheese. Initially these peptides are inactive within the sequence of the parent protein molecule and can be generated by gastrointestinal digestion of milk, fermentation of milk with proteolytic starter cultures, and/or hydrolysis by proteolytic enzymes. Milk derived peptides exert a number of health beneficial activities, even upon oral administration. Bioactive peptides have a great impact on major body systems including the digestive, nervous, endocrine, cardiovascular, diabetes type II, obesity, and immune systems. Antimicrobial peptides are also an important ingredient of innate immunity, especially at mucosal surfaces such as lungs and small intestine that are constantly exposed to a range of potential pathogens. Therefore, it plays an important role in boosting natural immune protection by reducing the risk of chronic diseases. Bioactive peptides are considered as potent drugs with well-defined pharmacological residues and also used to formulate health-enhancing nutraceuticals.     

Ultrasound-assisted generation of ACE-inhibitory peptides from casein hydrolyzed with nanoencapsulated protease

BACKGROUND: Bioactive peptides generated from milk proteins are eminent ingredients for functional foods and nutraceuticals. Amongst several approaches to release these peptides, hydrolysis of milk proteins with proteolytic enzymes is a promising choice. It is, however, required to inactivate the enzyme after a predetermined time, which leads to impurity of the final product. Immobilization of enzyme molecules can overcome this problem as it simplifies enzyme separation from the reaction mixture. A fungal protease from Aspergillus oryzea was encapsulated within nanoparticles yielded via silicification of polyamidoamine dendrimer template generation 0. It was used to hydrolyze the dominant milk protein (casein) in the absence or presence of sonication. The production of angiotensin converting enzyme (ACE)‐inhibitory peptides was monitored during hydrolysis. RESULTS: Sonication did not affect maximum ACE‐inhibitory activity but shortened the process sixfold. Ultrafiltration permeate of the centrifugal supernatant of casein solution hydrolyzed during sonication inhibited ACE activity as efficiently as the supernatant obtained from it. CONCLUSION: The protease from Aspergillus oryzea encapsulated within nanospheres is suitable for generation of ACE‐inhibitory peptides from casein. The nanoncapsulation procedure is simple, rapid and efficient. This may enable the industrial production of functional products from milk. Copyright © 2011 Society of Chemical Industry     

Antioxidant and antimicrobial peptidic hydrolysates from muscle protein sources and by-products

Bioactive peptides are short peptides approximately 2–30 amino acids in length. They are inactive within the sequence of the parent protein and can be released during gastrointestinal digestion, during food processing or by hydrolysis using commercial enzymes. Meat derived peptides have a myriad of bioactive potential including, antioxidant, antimicrobial, anti-thrombotic, ACE-I-inhibitory and cytomodulatory functions. Antioxidant and antimicrobial peptides isolated from meat muscle sources may be used as functional ingredient in food formulations to impart human health benefits and/or improve the shelf life of foods. This review collates information regarding peptidic hydrolysates with antioxidant and antimicrobial properties isolated from vertebrate and invertebrate muscle and by-products, identifying the sources, the isolation and characterisation techniques used, and the methods used to demonstrate these bioactivities in vitro.     

Functional role of bioactive peptides with special reference to cheeses

Growing perception about diet in relation to health has extended the necessity to explore the biologically active components present in native foods. In this review, bioactive peptides released from cheeses that may have important physiological functions are discussed. Bioactive encrypted peptides can be generated from precursor milk proteins during food processing via enzymatic hydrolysis and fermentation. Generally, biofunctionalities of peptides are latent within precursor proteins. Bioactive peptides liberated from cheeses exhibit numerous potential therapeutic roles: for example, angiotensinogen‐converting enzyme (ACE) inhibition, antioxidant, anti‐thrombotic, anti‐microbial, anti‐cancer and anti‐inflammatory. This article critically focuses on the functional roles of bioactive peptides derived from different cheeses.     

Bioactive peptides derived from milk proteins and their health beneficial potentials: an update

It has been well recognized that dietary proteins provide a rich source of biologically active peptides. Today, milk proteins are considered the most important source of bioactive peptides and an increasing number of bioactive peptides have been identified in milk protein hydrolysates and fermented dairy products. Bioactive peptides derived from milk proteins offer a promising approach for the promotion of health by means of a tailored diet and provide interesting opportunities to the dairy industry for expansion of its field of operation. The potential health benefits of milk protein-derived peptides have been a subject of growing commercial interest in the context of health-promoting functional foods. Hence, these peptides are being incorporated in the form of ingredients in functional and novel foods, dietary supplements and even pharmaceuticals with the purpose of delivering specific health benefits.     

Bioactive peptides: Production and functionality

Milk proteins exert a wide range of nutritional, functional and biological activities. Many milk proteins possess specific biological properties that make these components potential ingredients of health-promoting foods. Increasing attention is being focused on physiologically active peptides derived from milk proteins. These peptides are inactive within the sequence of the parent protein molecule and can be liberated by (1) gastrointestinal digestion of milk, (2) fermentation of milk with proteolytic starter cultures or (3) hydrolysis by proteolytic enzymes. Milk protein derived peptides have been shown in vivo to exert various activities affecting, e.g., the digestive, cardiovascular, immune and nervous systems. Studies have identified a great number of peptide sequences with specific bioactivities in the major milk proteins and also the conditions for their release have been determined. Industrial-scale technologies suitable for the commercial production of bioactive milk peptides have been developed and launched recently. These technologies are based on novel membrane separation and ion exchange chromatographic methods being employed by the emerging dairy ingredient industry. A variety of naturally formed bioactive peptides have been found in fermented dairy products, such as yoghurt, sour milk and cheese. The health benefits attributed to peptides in these traditional products have, so far, not been established, however. On the other hand, there are already a few commercial dairy products supplemented with milk protein-derived bioactive peptides whose health benefits have been documented in clinical human studies. It is envisaged that this trend will expand as more knowledge is gained about the multifunctional properties and physiological functions of milk peptides.     

Functional properties and health benefits of bioactive peptides derived from Spirulina: A review

Bioactive peptides represent specific sequences of amino acids that have biological activity with several health effects and potential applications, which can be obtained from diverse protein sources. Spirulina, the cyanobacterium known for its high protein content and therapeutic properties, has been investigated as a potential source of bioactive peptides. Some bioactive peptides derived from Spirulina are under study for their ability to offer specific health benefits, such as antimicrobial, antiallergic, antihypertensive, antitumor, and immunomodulatory properties. Bioactive peptide fractions from Spirulina biomass can be obtained through a series of operations, including cell lysis and protein extraction, enzymatic hydrolysis, potential bioactivity screening, fractionation, and purification. Potentially, Spirulina-derived peptide fractions can be applied as nutraceutical ingredients in foods and pharmaceuticals. This article reviews the functional properties and health benefits of bioactive peptides from Spirulina, and presents potential mechanisms by which bioactive components can be exploited in the development of novel foods with special health claims. In addition, this article describes recent developments in proteomics, bioactivity screening methods, and opportunities for designing future peptide-based foods.     

食物源ACE抑制肽的生产及构效关系研究进展

生物活性肽是蛋白质中隐藏着的可在体内发挥一定生理功能的活性肽段。目前已从食物蛋白中获得了具有免疫调节、抑菌、抗病毒、抗肿瘤、抗血栓形成、抗高血压等功能的多肽,其中血管紧张素转化酶(ACE)抑制肽是研究热点之一。ACE通过产具有升压作用的血管紧张素Ⅱ和降解扩张血管的舒缓激肽在调节血压中发挥着重要作用。ACE抑制肽可通过消化道水解、发酵和熟化过程、体外酶解和遗传重组方法而获得,并可作为功能因子添加到功能食品中,相关产品已上市或研发中。本文对ACE抑制肽的生产及其构效关系研究进展等进行综述。     

Milk-derived bioactive peptides: From science to applications

Milk proteins have received increasing attention as potential ingredients of health-promoting functional foods targeted at diet-related chronic diseases, such as cardiovascular disease, diabetes type two and obesity. To this end, growing interest has been focused on physiologically active peptides derived from milk proteins. These peptides are inactive within the sequence of the parent protein molecule and can be liberated by gastrointestinal digestion of milk, fermentation of milk with proteolytic starter cultures or hydrolysis by proteolytic enzymes. Milk protein-derived peptides have been shown under in vitro and in vivo conditions to exert a number of activities affecting the digestive, endocrine, cardiovascular, immune and nervous systems. A great variety of naturally formed bioactive peptides have been found in fermented dairy products, such as yoghurt, sour milk and cheese. Recently, industrial-scale technologies suitable for the industrial production of bioactive milk peptides have been developed. In addition, a few commercial food products supplemented with milk protein-derived bioactive peptides have been launched on limited markets. Some of these products carry clinically documented benefits, in particular for reduction of mild hypertension. The multifunctional properties of milk peptides appear to offer considerable potential for the development of many similar products in the near future.     

Antimicrobial peptides generated from milk proteins: a survey and prospects for application in the food industry. A review

Milk proteins constitute a natural reservoir of bioactive peptides with physiological and/or antimicrobial properties, the release of which requires hydrolysis of the precursor molecules by digestive proteases or by fermentation with proteolytic micro‐organisms. Depending on the digestive or microbial proteases used, an array of bioactive peptides would be released either from caseins or whey proteins, but only a small part of these peptides has so far been identified and characterised with respect to their antimicrobial activity. The antimicrobial peptides known thus far have proven to be potent inhibitors to the growth of a wide range of undesirable micro‐organisms of health or spoilage significance. Nevertheless, previous research work has largely been oriented towards their possible application in medicine, which has hindered their high potential as food‐grade biopreservatives and/or as supplements in functional foods. This review attempts to study the literature pertaining to antimicrobial peptides derived from major milk proteins (caseins, α‐lactalbumin and β‐lactoglobulin) upon hydrolysis either by digestive proteases or by fermentation with proteolytic lactic acid bacteria. Their possible application in the food industry and their mechanism of action will also be discussed. Reference antimicrobial peptides produced by living micro‐organisms as innate immune defence components against microbial infections will occasionally be invoked for comparison purposes.     

Anticancer activity of bovine α‐lactalbumin treated with microbial transglutaminase

This study investigated the effects of bovine α‐lactalbumin (α‐La) treated with microbial transglutaminase on human cancer cells, cell cultures and growth rate assays. The anticancer activity for 10 mg/mL of bovine α‐lactalbumin (α‐La) was measured as ～90% in a human colorectal cancer cell line HCT 116. For the human bone cancer cell line SJSA‐1, α‐La hydrolysis resulted in higher cytotoxicity compared to untreated tumour cells. The formation of polymers of α‐La was suppressed by the addition of ethylenediaminetetraacetic acid, indicating that polymers of α‐La are promoted by metal ions such as Ca²⁺. The effect of α‐La on the morphology of SJSA‐1 cells was manifested as morphological changes compatible with apoptosis. Bovine milk α‐La with and without microbial transglutaminase is considered a valuable food ingredient and a nutraceutical for human health.     

Enhancing enzymatic hydrolysis of food proteins and production of bioactive peptides using high hydrostatic pressure technology

BackgroundBioactive peptides (BPs) generated by hydrolysis of food proteins exhibit a broad spectrum of biological properties (antihypertensive, hypocholesterolemic, antimicrobial, antioxidant, etc.) in both in vitro and in vivo models. Initially obtained from milk and egg products, BPs have now largely been obtained from food byproducts such as marine, animal and plant biomasses. Amongst the various strategies being developed for BPs production, enzymatic hydrolysis (EH) is the most widely preferred due to its GRAS nature. However, the main challenge of EH is to decrease the time and quantity of enzyme, and improve yield and bioactivity of BPs.Scope and approachConsequently, innovative and efficient food technologies have been developed to satisfy these needs. High hydrostatic pressure (HHP) processing, a non-thermal technology, initially developed to extend food shelf-life, is being considered as a promising tool to improve the efficiency of EH and generate high value-added peptide fractions from various complex biomasses.Findings and conclusionsThis innovative and emerging technology enhances EH by inducing protein unfolding/denaturation, as well as activating the enzymes used while maintaining their nutritional and functional properties. This review discusses the state of the art of HHP technique, its applications in combination with EH, and potential challenges for the production of BPs from food-derived protein sources.     

Chemopreventive role of food-derived proteins and peptides: A review

Cancer is one of the leading causes of mortality and disability worldwide. Although great advances in cancer treatments such as chemotherapy, surgery, and radiation are currently being achieved, their application is associated with numerous and expensive adverse side effects. Epidemiological evidence has demonstrated that the consumption of certain foods potentially prevents up to 35% of cancer cases. Bioactive components are ubiquitous in nature, also in dietary food, providing an essential link in health maintenance, promotion, and prevention of chronic diseases, such as cancer. Development of bioactive proteins and peptides is a current and innovative strategy for cancer prevention/cure. A growing body of anticancer protein and peptides from natural sources has shown the ability to reduce tumor progression through multiple mechanisms including apoptotic, antiproliferative, antiangiogenic, and immunomodulatory activities. This review is focused on proteins and peptides from different food sources including plants, milk, egg, and marine organisms in which chemopreventive properties have been demonstrated. Other aspects such as mechanism of action, bioavailability, and identification and characterization of food-derived peptides by advance separated technologies are also included. This review highlights the potential application of food-derived peptides as functional food ingredients and pharmaceutical candidates in the auxiliary therapy of cancer.     

低致敏食品制备技术及其工业化应用研究进展

食物过敏是联合国粮农组织和世界卫生组织认定的全球性食品安全问题之一。在食品加工多元化的背景下,食物过敏患者要完全避免过敏原十分困难,研发低致敏食品对食物过敏患者的安全膳食至关重要。总结了低致敏食品制备技术的加工技术原理;以蒸煮、微波和烘烤为主的热加工技术通过加热诱导蛋白质变性的方式破坏致敏性构象性表位;高压、脉冲电场、脉冲光、低温等离子体、辐照和超声等非热加工技术可以通过过敏原蛋白结构修饰、多肽链断裂、新化学键的产生等方式直接破坏致敏性表位;酶水解、酶交联、糖基化、微生物发酵等其他加工方法则通过改变蛋白质构象或将蛋白质与糖类物质结合,破坏或隐藏过敏原致敏性表位。另外,对工业化低致敏蛋白配料的加工方法和生产现状进行了阐述分析。基于酶法水解的部分水解乳蛋白和深度水解乳蛋白已经可以工业化生产,其他消减食物致敏性的方法以及其他低致敏蛋白配料值得进一步研究。希望可以为工业化生产低致敏食品提供参考。     

Bioactive peptides in dairy products

Bioactive peptides are hydrolysates with specific amino acid sequences that exert a positive physiological influence on the body. They are inert within the native protein, but once cleaved from the native protein by microbial or added enzymes and/or gastrointestinal enzymes during the digestive process, they apply their beneficial traits. Dairy products, particularly fermented products, are potential sources of bioactive peptides: several of them possess extra‐nutritional physiological functions that qualify them to be classified under the ‘Functional Foods’ label. Biological peptides in milk, the methods of their generation and their prevalence in dairy products are reviewed along with the reported health benefits and safety aspects.     

Exogenous opioid peptides derived from food proteins and their possible uses as dietary supplements: A critical review

Endogenous opioid peptides are neuro-hormones and neurotransmitters involved in several physiological actions such as stress reactions, nociception control, sedation, breathing tone, depression, hypotension, appetite, digestion, etc. It is now clear that hydrolysis by the digestion of certain food-proteins can lead to the production of bioactive peptides. Commonly diffused foods like milk, wheat, meat, and spinach may produce after enzymatic digestion a variable amount of opioid peptides. The aim of this review is to provide arising perspectives on opioid peptides, focusing on their production from milk, their potential benefits, drawbacks, and safety issues related to infants’ feeding.     

Initial proteolysis of milk proteins and its effect on formation of ACE-inhibitory peptides during gastrointestinal proteolysis: a bioinformatic, in silico, approach

Angiotensin-I-converting enzyme (ACE)-inhibitory peptides are encrypted in milk protein sequences. They may express an antihypertensive effect if they are released by proteolysis in foods and/or during gastrointestinal digestion. A bioinformatic, in silico, approach was developed to evaluate how systematic initial proteolysis, i.e. cleavage after one specific type of amino acid (C-end) at a time in milk proteins, influence the formation of ACE-inhibitory peptides by subsequent gastrointestinal proteolysis. Computer simulation was done and a peptide QSAR model was used to estimate the combined ACE inhibition by digested proteins. Initial proteolytic cleavage at the C-end of amino acids isoleucine and proline gave, based on calculations, increased effect of ACE-inhibitory peptides after gastrointestinal proteolysis of milk proteins. Cleavage after most other amino acid residues had little or no effect. Results indicate that initial proteolysis in foods have to be specific in order to increase formation of bioavailable ACE-inhibitory peptides during gastrointestinal digestion.     

Bioactive peptides in dairy products: synthesis and interaction with proteolytic enzymes

Food proteins are sources of peptides with various biological activities, such as opioids, mineral carriers, antihypertensives, immuno-stimulants, antithrombotics and antigastrics. These bioactive peptides are generated in vivo, in vitro and during food processing. Bioactive peptides are largely found in milk, fermented milks and cheeses. Proteolytic enzymes naturally occurring in milk, and enzymes from lactic acid bacteria or from exogenous sources contribute to the generation of bioactive peptides. Dairy processing conditions such as cheese ripening are also relevant. Once produced, bioactive peptides play a significant role in cheesemaking by selectively inhibiting proteolytic enzymes of lactic acid bacteria and subsequently affecting cheese quality. Sensitivity to inhibition is highly specific: enzymes of the same biochemical class and strains of the same species differ. Bioactive peptides also inhibit dairy spoilage enzymes.