Peptides Derived from Foods as Supportive Diet Components in the Prevention of Metabolic Syndrome

Metabolic syndrome (MSyn) includes physiological, biochemical, clinical, and metabolic abnormalities, leading to an increase in health problems like obesity, dyslipidemia, cardiovascular diseases, and diabetes, which contribute to an increase in mortality rate. One of the main factors having a key impact on our health is the food we consume. Thus, scientists work towards the discovery of novel bioactive compounds with therapeutic potential to address MSyn. According to scientific reports, peptides derived from food proteins exhibit bioactivities important for the prevention of MSyn diseases; that is, they regulate blood pressure and glycemia; reduce cholesterol level and body mass; and scavenge free radicals. The aim of this review is to study the potential role of peptides in the prevention of MSyn. Particularly peptides which exhibit the following activities: antihypertensive [angiotensin‐converting enzyme (ACE) inhibition (EC 3.4.15.1)], antidiabetic [dipeptidyl peptidase IV (DPP‐IV) (EC 3.4.14.5)/α‐glucosidase (EC 3.2.1.20)/α‐amylase (EC 3.2.1.1) inhibition)], cholesterol level reduction, antioxidative, and obesity prevention, were studied. If possible, special attention is paid in the review to the bioactivities of peptides that were measured in vivo. Some examples of peptides showing dual or multiple action against MSyn targets are presented. Moreover, using the database of bioactive peptide sequences (BIOPEP) we made a list of peptides serving simultaneous functions in counteracting MSyn dysfunctions. Such an approach may simplify the discovery of MSyn preventive peptides, as well as highlight some of them as potent bioactive ingredients that may be incorporated into foods. Moreover, the research strategy involving the in silico and in vitro/in vivo methodologies may be useful in the production of food protein hydrolysates supporting the treatment of MSyn dysfunctions.     

Food protein-based materials as nutraceutical delivery systems

Incorporation of bioactive compounds–such as vitamins, probiotics, bioactive peptides, and antioxidants etc.–into food systems provide a simple way to develop novel functional foods that may have physiological benefits or reduce the risks of diseases. As a vital macronutrient in food, proteins possess unique functional properties including their ability to form gels and emulsions, which allow them to be an ideal material for the encapsulation of bioactive compounds. Based on the knowledge of protein physical–chemistry properties, this review describes the potential role of food proteins as substrate for the development of nutraceutical delivery systems in the form of hydrogel, micro-, or nano- particles. Applications of these food protein matrices to protect and delivery-sensitive nutraceutical compounds are illustrated, and the impacts of particle size on release properties are emphasized.     

A New Frontier in Soy Bioactive Peptides that May Prevent Age‐related Chronic Diseases

During gastrointestinal digestion or food processing of proteins, small peptides can be released and may act as regulatory compounds with hormone‐like activities. Numerous biologically active peptides (bioactive peptides) have been identified. Most bioactive peptides are derived from milk and dairy products, with the most common being angiotensin converting enzyme inhibitory peptides. Soybean protein and soybean derived peptides also play an important role in soybean physiological activities, particularly those related to the prevention of chronic diseases. However, the bioactive potential of soybean derived bioactive peptides is yet to be fully appreciated. After a general introduction of approaches and advances in bioactive peptides from food sources, this review focuses on bioactive peptides derived from soybean proteins and their physiological properties. Technological approaches to generate bioactive peptides, their isolation, purification, characterization, and quantification, and further application in food and drug design are also presented. Safety concerns, such as potential toxicity, allergenicity, and sensory aspect of these peptides are likewise discussed.     

Bioactive peptides as natural antioxidants in food products – A review

BackgroundDiseases related to oxidative stress and food quality decay are of major concern worldwide as they can lead to economic losses in both public health and food production. The antioxidant peptides, extracted from food proteins, can be explored as natural new drug and food ingredient.Scope and approachAntioxidant peptides are extracted from non-antioxidant precursor proteins from different origin by the activity of either proteolytic microorganisms or isolated enzymes. In the present review, the main sources of bioactive peptides will be discussed. Moreover, the current strategies to obtain these compounds as well as their health benefits and in vivo biological effects will be evaluated. Considerations for further research and development of strategies to increase the knowledge about this underexplored activity of peptides will be also considered.Key findings and conclusionsBioactive peptides' content and profile differ according to the matrix studied and the method used. The utilization of fermentation processes and enzymes has been established to obtain antioxidant bioactive peptides from proteins, being isolated enzymes the most commonly used method, due to their superior control over releasing and obtaining targeted peptides. Antioxidant peptides have the ability to reduce the formation of oxidative products along with the induction of antioxidant enzymes in vivo. However, at this stage of development more in vivo studies are needed in order to evaluate the specific effects on the health of selected antioxidant peptides. In food technology, successful application in meat products strengthens the role of selected peptides as antioxidant additives, although there is a need to observe the effects of the isolated bioactive peptides in other food matrices along with studies to scale-up its production.     

Bioactive Peptides Derived from Seaweed Protein and Their Health Benefits: Antihypertensive,Antioxidant, and Antidiabetic Properties

Cardiovascular diseases and diabetes are the biggest causes of death globally. Therefore, prevention of these diseases is a focus of pharmaceuticals and functional food manufacturers. This review summarizes recent research trends and scientific knowledge in seaweed protein‐derived peptides with particular emphasis on production, isolation and potential health impacts in prevention of hypertension, diabetes and oxidative stress. The current status and future prospects of bioactive peptides are also discussed. Bioactive peptides have strong potential for use in therapeutic drug and functional food formulation in health management strategy, especially cardiovascular disease and diabetes. Seaweeds can be used as sustainable protein sources in the production of these peptide‐based drugs and functional foods for preventing such diseases. Many studies have reported that peptides showing angiotensin converting enzyme inhibition, antihypertensive, antioxidative and antidiabetics activities, have been successfully isolated from seaweed. However, further research is needed in large‐scale production of these peptides, efficient isolation methods, interactions with functional foods and other pharmaceuticals, and their ease to digestion in in vivo studies and safety to validate the health benefits of these peptides.     

Antioxidant peptides: Overview of production,properties, and applications in food systems

In recent years, several studies have reported the beneficial effects of antioxidant peptides in delaying oxidation reactions. Thus, a growing number of food proteins have been investigated as suitable sources for obtaining these antioxidant peptides. In this study, some of the most critical developments in the discovery of peptidic antioxidants are discussed. Initially, the primary methods to release, purify, and identify these antioxidant peptides from various food-derived sources are reviewed. Then, computer-based screening methods of the available peptides are summarized, and methods to interpret their structure–activity relationship are illustrated. Finally, approaches to the large-scale production of these bioactive peptides are described. In addition, the applications of these antioxidants in food systems are discussed, and gaps, future challenges, and opportunities in this field are highlighted. In conclusion, various food items can be considered promising sources to obtain these novel antioxidant peptides, which present various opportunities for food applications in addition to health promotion. The lack of in-depth data on the link between the structure and activity of these antioxidants, which is critical for the prediction of possible bioactive amino acid sequences and their potency in food systems and in vivo conditions (rather than in vitro systems), requires further attention. Consequently, future collaborative research activities between the industry and academia are required to realize the commercialization objectives of these novel antioxidant peptides.     

生物活性肽的研究进展理论基础与展望

随着具各种生物活性的短肽的不断发现,其研究和开发日益受到各国科学家的关注。大量科学研究表明,通过选择适当的蛋白酶,水解的蛋白质可以得到大量的具有各种生物功能的生物活性肽,这些活性肽不仅具有极其广泛的活性和多样性,而且其来源丰富、成本低、安全性好。操作简单、便于工业化生产,因此已成为科学家们研究的新热点。例如：酪蛋白是哺乳动物乳中含量最丰富的蛋白质,长期以来,被人们视为一种营养蛋白,但近年来的研究结果表明,它是生物活性肽的重要来源,到目前为止,已经有数十种生物活性肽被水解和辨认出来。所以,生物活性肽非常好的研究与开发前景。     

改善心血管健康的食源性生物活性肽构效关系研究进展

食物源生物活性肽作为可改善健康状况的营养成分可由动植物食品在人体内消化或加工过程中产生,并表现出抗氧化、免疫调节、调节阿片样受体及抗菌、降压、降血脂、抗血栓等多种生理活性。通过调节和改善人体生理功能,生物活性肽可用于预防和治疗心血管疾病等慢性病。活性肽的来源、结构对其功能性质有重要影响。本文综述了与心血管健康有关的活性肽的构效关系研究进展,并对其研究前景进行展望。     

Bioactive peptides derived from milk proteins. Structural,physiological and analytical aspects

The primary function of dietary proteins is to supply the body adequately with indispensable amino acids and organic nitrogen. Little attention has been paid up to date to milk proteins, in particular caseins, that are currently the main source of biologically active peptides, although other animal as well as vegetable proteins are known to contain potentially bioactive sequences. Such regulatory peptides can be released by enzymatic proteolysis of caseins in vitro and in vivo and may act as potential physiological modulators of metabolism during the intestinal digestion of the diet. It has been proved that bioactive peptides derived from caseins, such as β-casomorphins and phosphopeptides, can be released during gastrointestinal passage. It is also evident that peptides originating from food proteins should be taken into account as potential modulators of various regulatory processes in the body. The possible regulatory effects concern nutrient uptake (phosphopeptides, casomorphins), postprandial hormone secretion (casomorphins), immune defense (immunopeptides, casokinins, casomorphins) and neuroendocrine information transfer (casokinins). The advances in the research field of bioactive peptides are driven by a molecular understanding of biological processes, and analytical techniques are a critical component of this understanding. Different up-to-date methods, including peptide synthesis and immunochemistry, have been applied to the chemical characterization of bioactive peptides. Especially casein derived peptides have already found interesting applications, both as dietary supplements (phosphopeptides) and as pharmaceutical preparations (phosphopeptides, β-casomorphins). The question of'what kinds of bioactive peptides are beneficial and desirable as food constituents or as drugs' should be always carefully examined. However, the possibilities for the design of dietary products and ‘natural’ drugs look promising.     

生物活性肽和肠道菌群相互作用研究进展

生物活性肽是对生物机体的生命活动具有积极作用的肽类化合物,近年来逐渐成为食品、保健食品以及特殊医学用食品等领域的研究热点之一.研究表明,肠道中微生物产生的蛋白酶作用于食物中的蛋白质,可以产生生物活性肽.另一方面,生物活性肽对肠道菌群的结构具有明显的调节作用,而肠道菌群结构的改变对宿主的健康产生重要的影响.本文对生物活性...     

乳在哺乳动物进化中的作用

随着常乳、初乳营养值的研究和生物活性物质的不断发现，特别是通过用适当酶水解乳蛋白获得的各类生物活性物质的不断增多，科学家越来越发现乳在人民生活中具有不可替代的作用，它不仅为其后代提供了最适宜的营养，而且在哺乳动物生长、发育、进化和各种相关的生理活动中起极其重要的作用，可以这样说：没有哺乳，就没有哺乳动物，更没有哺乳动物的繁荣。这些研究结果提示：乳及其营养价值、生物活性物质和生物学意义必将成为食品科学、营养科学、医学和生物学研究的热门课题。     

A Review of Potential Marine-derived Hypotensive and Anti-obesity Peptides

Bioactive peptides are food derived components, usually consisting of 3–20 amino acids, which are inactive when incorporated within their parent protein. Once liberated by enzymatic or chemical hydrolysis, during food processing and gastrointestinal transit, they can potentially provide an array of health benefits to the human body. Owing to an unprecedented increase in the worldwide incidence of obesity and hypertension, medical researchers are focusing on the hypotensive and anti-obesity properties of nutritionally derived bioactive peptides. The role of the renin–angiotensin system has long been established in the aetiology of metabolic diseases and hypertension. Targeting the renin–angiotensin system by inhibiting the activity of angiotensin-converting enzyme (ACE) and preventing the formation of angiotensin II can be a potential therapeutic approach to the treatment of hypertension and obesity. Fish-derived proteins and peptides can potentially be excellent sources of bioactive components, mainly as a source of ACE inhibitors. However, increased use of marine sources, poses an unsustainable burden on particular fish stocks, so, the underutilized fish species and by-products can be exploited for this purpose. This paper provides an overview of the techniques involved in the production, isolation, purification, and characterization of bioactive peptides from marine sources, as well as the evaluation of the ACE inhibitory (ACE-I) activity and bioavailability.     

Bioactive protein hydrolysates in the functional food ingredient industry: Overcoming current challenges

Meat proteins and associated by-products can be used as a source of bioactive hydrolysates and peptides with potential for use as functional food ingredients. Functional foods are foods that have a potentially positive effect on health, beyond basic nutrition. Numerous bioactive peptides, including angiotensin-I-converting enzyme (ACE-I, EC 3.4.15.1) and dipeptidyl peptidase-IV (DPP-IV, EC 3.4.14.5) inhibitors, have been generated from meat by-product proteins to date. However, in order to use and commercialize bioactive hydrolysates and peptides as food ingredients, a number of significant challenges must first be overcome. This article gives an overview of the current state-of-the-art of meat-derived bioactive hydrolysate and peptide uses in the food industry. It also reviews frequent challenges faced when developing biologically active hydrolysates and peptides as food ingredients. These challenges include, but are not limited to, high production costs, negative sensory attributes in end products, taste modifications of carrier food products and compliance with, for example, the European Food Safety Authority (EFSA), the Food and Drug Administration (FDA), and other regulatory bodies in China, or Japan, as well as potential toxicity or allergenicity. We suggest strategies that may assist in overcoming these challenges, focusing on those that may be used to improve the taste attributes of the end products.     

Antioxidant and metal chelating activities of Phaseolus vulgaris L. var. Jamapa protein isolates, phaseolin and lectin hydrolysates

A search in a database of potential bioactive short sequences in food proteins reveals that bioactive peptides with a variety of beneficial effects for cardiovascular health are present in the sequence of common bean proteins, including bioactive sequences with antioxidant properties. A protein isolate, the storage protein phaseolin and a lectin extract from Phaseolus vulgaris L. var. Jamapa, were hydrolyzed by treatment with pepsin and pancreatin in order to investigate the possible release of peptides with antioxidant and metal chelating properties. Antioxidant activity was determined in Caco-2 cells exposed to a free radical generator, and iron and copper chelating activities were determined using colorimetric methods. The highest antioxidant activity, 71% inhibition, was found in the hydrolyzed protein isolate. Copper and iron chelating activities were highest in the lectin and phaseolin hydrolysates, 53% and 81%, respectively. Thus, experimental data indicates, as suggested by the database search, that antioxidant peptides are abundant in pepsin-pancreatin hydrolysates, which may represent a valuable health-promoting property in common bean.     

Bioactive peptides from nuts: A review

Oxidative stress occurs because of an imbalance in the production of reactive oxygen species. Nuts are rich in bioactive compounds, including phenolic compounds, tannins, and phytosterols. Although nuts are widely consumed because of their beneficial effects on nutrition and health, there is limited information about bioactive peptides from nuts. Pine nut and walnut-derived peptides are the most studied because these nuts contain a higher amount of protein. Different biological activities have been demonstrated for nut peptides; many of them exhibit antioxidant, anticancer, antihypertensive, antidiabetic, immunomodulatory, antiseizure, or neuroprotective activity. Recent studies have focused on increasing the bioactivity of identified bioactive peptides by applying new technologies and chemosynthetic strategies. Research tendency points to the generation of peptides with specific sequences for application in specific diseases. Nut bioactive peptides can become key functional ingredients for food, pharmaceuticals, or cosmetics.     

Milk biologically active components as nutraceuticals: review

Milk contains components that provide critical nutritive elements, immunological protection, and biologically active substances to both neonates and adults. Milk proteins are currently the main source of a range of biologically active peptides. Concentrates of these peptides are potential health-enhancing nutraceuticals for food and pharmaceutical applications. Several bioactive peptides may be used as nutraceuticals, for example, in the treatment of diarrhea, hypertension, thrombosis, dental diseases, as well as mineral malabsorption, and immunodeficiency. Minor whey proteins, such as lactoferrin, lactoperoxidase, lysozyme, and immunoglobulins, are considered antimicrobial proteins. Milk also contains some natural bioactive substances. These include oligosaccharides, fucosylated oligosaccharides, hormones, growth factors, mucin, gangliosides, and endogenous peptides, which are present in milk at secretion. Most of the claimed physiological properties of milk bioactive components have been carried out in vitro or in animal model systems, and these hypothesized properties remain to be proven in humans. Whether these milk bioactive components will replace drugs entirely in the immediate future is still unclear, but the increasing appreciation of "drug foods" or nutraceuticals plays a complementary rather than a substitutional role to the synthetic pharmacological drugs.     

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.     

Bioactive peptides derived from bovine whey proteins: opioid and ace-inhibitory peptides

Regulatory peptides can be released by enzymatic proteolysis of food proteins and may act as potential physiological modulators of metabolism during the intestinal digestion of the diet. The possible regulatory effects of peptides relate to nutrient uptake, immune defence, opioid and antihypertensive activities. Milk proteins, especially caseins, are an important source of these bioactive peptides. During recent years, major whey protein components, α-lactalbumin and β-lactoglobulin, were also shown to contain bioactive sequences. Peptides showing opioid and angiotensin I-converting enzyme (ACE) inhibitory activity were found in α-lactalbumin and β-lactoglobulin. Opioid peptides, α-lactorphin and β-lactorphin, were liberated during in vitro proteolysis of bovine whey proteins, and pharmacological activity was observed at micromolar concentrations. Whey hydrolysates showed ACE-inhibitory activity after proteolysis with different digestive enzymes, and several active peptides were identified. The results demonstrated the existence of several biologically active whey-derived peptides and hydrolysates. The findings of the study can be exploited in the development of foods with special health claims (e.g. treatment of hypertension) as well as in identifying new applications in food.     

Food‐derived immunomodulatory peptides

Food proteins contain specific amino acid sequences within their structures that may positively impact bodily functions and have multiple immunomodulatory effects. The functional properties of these specific sequences, also referred to as bioactive peptides, are revealed only after the degradation of native proteins during digestion processes. Currently, milk proteins have been the most explored source of bioactive peptides, which presents an interesting opportunity for the dairy industry. However, plant‐ and animal‐derived proteins have also been shown to be important sources of bioactive peptides. This review summarizes the in vitro and in vivo evidence of the role of various food proteins as sources of immunomodulatory peptides and discusses the possible pathways involving these properties. © 2016 Society of Chemical Industry     

Peptides from milk proteins and their properties

This review has attempted to study the literature pertaining to peptides derived from milk proteins. Hydrolysis of milk proteins to generate peptides has been practiced for a long time and it was recognized early on in this process that the taste of hydrolyzates might hinder use of these products in food formulations. Modification of protein is necessary to form a more acceptable or utilizable product, to form a product that is less susceptible to deteriorative reactions and to form a product that is of higher nutritionall quality. Modifications may be achieved by a number of chemical and enzymatic means. This review has considered only enzymatic modification of dairy proteins. Modified proteins contain peptides and some of these peptides have been purified and their functionalities have been compared with unmodified proteins. This paper has examined the literature pertaining to improvement in functionality of enzyme-modified proteins. Improvements in solubility, emulsification, foaming and gelation were examined. There is limited information available on the sequence of the peptides necessary to improve the functional characteristics of proteins. Knowing the sequences of desirable functional peptides can lead to genetic alteration of proteins to improve functionality. Addition of synthetic peptides to intact proteins may be another way in which the functionality of proteins can be augmented. Some of the peptides in milk proteins are capable of affecting biological functions of an organism. These effects can be antimicrobial and probiotic, i.e., prevent the growth and proliferation of undesirable and pathogenic organisms, or they may promote the growth of desirable bacteria in the digestive tract of humans and animals. Peptides derived from milk protein have been shown to exert digestive and metabolic effects as well. They may also influence the immune system. These biological effects may play an important role in the development of medical foods that treat or mitigate the effects of diseases. Proteins are allergens and therefore it is possible that products derived from modification of proteins may also be allergens. The known literature about the allergenicity of peptides derived from milk proteins has been examined in this article. Last, but not the least, the taste attributes of peptides is also considered. Bitterness of hydrolyzates is a common occurrence and the origins of these bitter peptides and possible ways of mitigating this sensory defect has been discussed. Many of the peptides that enhance functionality and exert biological activity are likely to be bitter. Therefore, the bitter taste of hydrolysis products has to be dealt with in boosting the functional or nutraceutical aspects of foods containing these peptides. Analytical techniques for sequencing peptides have become more accessible and purification of peptides is commercially feasible. Computer based modeling techniques have aided the prediction of structures in these peptides. These advances, coupled with the advances in biotechnology, promise to revolutionize the future of nutraceutical and functional foods.