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Biochemical Properties of Peptides Encrypted in Bovine Milk Proteins
Abstract
Milk proteins are precursors of many different biologically active peptides. These peptides are inactive within the protein sequence, requiring enzymatic proteolysis for release of the bioactive fragment from the proteins precursor. It is evident that activated peptides originating from milk proteins should be taken into account as potential modulators of various regulatory processes in the body. Activated peptides are potential modulators of various regulatory processes in the living system: immuno-modulatory peptides stimulate the activities of cells of the immune system and several cytomodulatory peptides inhibit cancer cell growth, antimicrobial peptides kill sensitive microorganisms, angiotensin-I-converting enzyme (ACE)-inhibitory peptides exert an hypotensive effect, opioid peptides are opioid receptor ligands which can modulate absorption processes in the intestinal tract, mineral binding peptides may function as carriers for different minerals, especially calcium, antithrombotic peptides inhibit fibrinogen binding to a specific receptor region on the platelet surface and inhibit aggregation of platelets. Moreover, many milk-derived peptides reveal multifunctional properties, i.e. specific peptide sequences having two or more different biological activities have been reported. Bioactive peptides can interact with target sites (e.g. receptors, enzymes) at the luminal side of the intestinal tract, or they could be absorbed and reach any potential site of action in the system to elicit physiological effects. Bioactive peptides encrypted in bovine milk proteins can be produced on an industrial-scale and are claimed to be health enhancing components for functional foods, nutraceuticals and pharmaceutical preparations that are used to reduce risk of disease or to enhance certain physiological functions.
... The bovine raw milk contains a variety of endogenous peptides. Many of them exert bioactive functions, such as immunomodulatory effects and antimicrobial or mineral binding activities [1,2]. Native peptides are cleaved from the proteins by proteases naturally present in milk [1]. ...
... Many of them exert bioactive functions, such as immunomodulatory effects and antimicrobial or mineral binding activities [1,2]. Native peptides are cleaved from the proteins by proteases naturally present in milk [1]. Plasmin, the dominant protease in bovine milk, shows a high specificity for β-, α S1 -, and α S2 -casein with only low or no activity towards κ-casein, β-lactoglobulin, and α-lactalbumin [3][4][5]. ...
... However, several well-known bioactive peptides were identified. For example, β-casein peptides Ala177 to Arg183 and Tyr193 to Arg202, which belong to the class of β-casokinins with known ACE-inhibitory properties [1], are located in regions represented by many unmodified peptides. A similar trend was observed for a β-casein phosphopeptide (Lys29 to Thr41) with mineral binding properties [1]. ...
Bovine milk contains a variety of endogenous peptides, partially formed by milk proteases that may exert diverse bioactive functions. Milk storage allows further protease activities altering the milk peptidome, while processing, e.g., heat treatment can trigger diverse chemical reactions, such as Maillard reactions and oxidations, leading to different posttranslational modifications (PTMs). The influence of processing on the native and modified peptidome was studied by analyzing peptides extracted from raw milk (RM), ultra-high temperature (UHT) milk, and powdered infant formula (IF) by nano reversed-phase liquid chromatography coupled online to electrospray ionization (ESI) tandem mass spectrometry. Only unmodified peptides proposed by two independent software tools were considered as identified. Thus, 801 identified peptides mainly originated from αS- and β-caseins, but also from milk fat globular membrane proteins, such as glycosylation-dependent cell adhesion molecule 1. RM and UHT milk showed comparable unmodified peptide profiles, whereas IF differed mainly due to a higher number of β-casein peptides. When 26 non-enzymatic posttranslational modifications (PTMs) were targeted in the milk peptidomes, 175 modified peptides were identified, i.e., mostly lactosylated and a few hexosylated or oxidized peptides. Most modified peptides originated from αS-caseins. The numbers of lactosylated peptides increased with harsher processing.
... Bu biyoaktif peptitlerin biyolojik aktivitesi, aminoasitlerin çeşidine ve dizilişine bağlıdır (Beermann ve Hartung, 2012). Biyoaktif peptitler, gıdalar ile alındıktan veya sindirim sisteminde üretildikten sonra bağırsakta hedef bölgelerle etkileşime girer ve daha sonra emilerek organlara ulaşır (Kitts ve Weiler, 2003;Meisel, 2005). ...
... α-Laktorfin, kasomorfinler gibi morfine benzer yapıda olup analjezik özelliktedir. Kasomorfinler ve α-laktorfinin aksine, κkazein ve laktoferrinin parçalanmasıyla üretilen kasokinler ve laktoferoksinler opioid antagonistleri olarak işlev görürler, yani morfin benzeri maddelerin etkisini önleyebilirler (Meisel, 2005). Ayrıca α-La'nin triptofan aminoasidince zengin olması, beyinde serotonin sentezini de arttırabilmektedir. ...
... Kazein ve laktoferrinin enzimatik sindirimi ile oluşan biyoaktif peptitler antitümor ve apoptoz etki gösterirler. Bundan dolayı antikarsinojen özelliktedirler (Meisel, 2005;Yang ve ark., 2004). Ayrıca insan sütünden elde edilen α-laktalbümin ve türevleri apoptoz gibi mekanizmalarla hücrelerin ölümünü uyarmıştır (Svanborg ve ark., 2003). ...
In recent years, apart from the nutritional values of foods, functional properties have also gained importance. Bioactive peptides are the fragmentation products of proteins that have a positive effect on human health. Bioactive peptides in cow's milk are released as a result of hydrolysis of milk proteins with proteolytic enzymes. Bioactive peptides have biochemical and physiological properties such as immune regulation, mineral binding, antimicrobial, antihypertensive, opioid, anti-oxidative, anti-ulcerative, antithrombotic, antitumor and apoptosis. In this review, bioactive peptides in milk and milk products and their antimicrobial properties and effects on human health were evaluated.
... Bioactive peptides, usually containing 2-40 amino acid residues, are peptide compounds that are beneficial to the life activities of organisms or have physiological effects [1,2]. A large number of studies have shown that some oligopeptides have immunoregulatory [3], antibacterial [4], antioxidant [5], antihypertensive [6], and other properties. Bioactive peptides, which are not active in the precursor protein, are usually released from proteins by acid hydrolysis, alkali hydrolysis, or enzymatic hydrolysis, of which enzymatic hydrolysis is the least destructive and the most commonly used. ...
... Peptides with a molecular weight lower than 3000 Da, 1000 Da, and 500 Da in the PPs accounted for 96.56%, 82.75%, and 54.19%, respectively ( Figure 5 and Table 4), indicating that the majority of the PPs were peptides composed of less than 20 amino acid residues. As bioactive peptides usually contain 2-20 amino acid residues [3,4], this result indicates that the prepared PPs may contain a variety of bioactive peptides and may exhibit good biological activity. ...
Marine bacterial proteases have rarely been used to produce bioactive peptides, although many have been reported. This study aims to evaluate the potential of the marine bacterial metalloprotease A69 from recombinant Bacillus subtilis in the preparation of peanut peptides (PPs) with antioxidant activity and angiotensin-converting enzyme (ACE)-inhibitory activity. Based on the optimization of the hydrolysis parameters of protease A69, a process for PPs preparation was set up in which the peanut protein was hydrolyzed by A69 at 3000 U g−1 and 60 °C, pH 7.0 for 4 h. The prepared PPs exhibited a high content of peptides with molecular weights lower than 1000 Da (>80%) and 3000 Da (>95%) and contained 17 kinds of amino acids. Moreover, the PPs displayed elevated scavenging of hydroxyl radical and 1,1-diphenyl-2-picryl-hydrazyl radical, with IC50 values of 1.50 mg mL−1 and 1.66 mg mL−1, respectively, indicating the good antioxidant activity of the PPs. The PPs also showed remarkable ACE-inhibitory activity, with an IC50 value of 0.71 mg mL−1. By liquid chromatography mass spectrometry analysis, the sequences of 19 ACE inhibitory peptides and 15 antioxidant peptides were identified from the PPs. These results indicate that the prepared PPs have a good nutritional value, as well as good antioxidant and antihypertensive effects, and that the marine bacterial metalloprotease A69 has promising potential in relation to the preparation of bioactive peptides from peanut protein.
... The antiproliferative and apoptosis-inducing peptides may be useful in the treatment of cancer, whilst the cell growthpromoting peptides have advantages in promoting the development of newborns' digestive systems. Casomorphins, -lactorphin, -lactorphin, Lactoferroxins, Casoxins, Casokinin, Lactokinins, Immunopeptides, Lactoferricin, Casoplatelins, and Phosphopeptides are examples of bioactive peptides discovered in milk (Meisel 2005) [69] L-C Arnitine Lysine and methionine, two important amino acids, serve as precursors and cofactors for the production of carnitine, which mostly takes place in the liver. The kidney and brain can also produce carnitine. ...
... The antiproliferative and apoptosis-inducing peptides may be useful in the treatment of cancer, whilst the cell growthpromoting peptides have advantages in promoting the development of newborns' digestive systems. Casomorphins, -lactorphin, -lactorphin, Lactoferroxins, Casoxins, Casokinin, Lactokinins, Immunopeptides, Lactoferricin, Casoplatelins, and Phosphopeptides are examples of bioactive peptides discovered in milk (Meisel 2005) [69] L-C Arnitine Lysine and methionine, two important amino acids, serve as precursors and cofactors for the production of carnitine, which mostly takes place in the liver. The kidney and brain can also produce carnitine. ...
... Yüksek derişimdeki KFP'lerin negatif yükleri onların proteolize karşı daha da dirençli olmalarını sağlamaktadır (Silva ve Malcata, 2005;Korhonen ve Pihlanto-Leppälä, 2006). Ayrıca bu aminoasitlerin özellikle fosfat gruplarındaki negatif yüklü yan zincirleri mineraller için bağlanma bölgeleri oluşturmaktadır (Korhonen ve Pihlanto-Leppälä, 2006;Meisel, 2005). Kazeinomakropeptitler (KMP) kalsiyum, magnezyum ve demir gibi makro elementlerin yanı sıra çinko, bakır, nikel, kobalt ve selenyum gibi oligoelementler için de bağlanma bölgelerine sahiptir. ...
... Lactobacillus GG ile fermente edilmiş UHT sütünün pepsin/tripsin tarafından hidrolizinin sonucunda αs1 ve α-laktalbuminden birkaç opioid peptit salgıladığı belirlenmiştir (Rokka ve ark., 1997). Opioid aktiviteye sahip olan biyoaktif peptitler sosyal davranışların düzenlenmesi, boşaltım hızının azalması, amino asit transferinin düzenlenmesi, insülin ve somatostatin hormonlarının salgılanması gibi önemli işlevlerin gerçekleşmesinde önemli rol oynadıkları tespit edilmiştir (Meisel, 2005 (Xu, 1998). Serum proteinlerinden proteoz-peptonun, plazmin enzimi ile hidrolizi sonucu PP 8 (f1-28) peptiti oluşmakta ve bu peptitin opioid agonist aktiviteye sahip olduğu bildirilmektedir. ...
Proteinler insan sağlığı için önemli organik maddeler olup, vücut için gerekli tüm aminoasitleri sağlamaktadırlar. Süt proteinleri çok önemli biyoaktif peptit kaynağı olarak kabul edilmektedir. Sığır sütü, kolostrum ve diğer süt türleri doğal biyoaktif peptitlerin en önemli doğal kaynağı olarak görülmektedir. Biyoaktif peptitler sütten; kazein ve serum proteinlerinden elde edilebilir. Sütten elde edilen biyoaktif peptitler gıdalarda sağlığı geliştiren maddeler olarak tanımlanmıştır. Bu peptitler insanlarda sinir, gastrointestinal, kardiyovasküler ve immün sistemin gelişmesine katkı sağlamaktadır. Böylece peptitler kanser, osteoporoz, hipertansiyon ve diğer sağlık sorunlarının önlenmesinde hayati bir rol oynar. Biyolojik aktivitenin çoğunluğu doğal proteinlerin birincil sekansıdır ve enzimatik hidroliz, proteoliz ya da mikrobiyal fermantasyon sonucunda serbest bırakılabilmektedir. Fermente süt ürünlerinde, ekşi sütlerde, peynir altı suyunda ve olgunlaşmış peynirlerde biyoaktif peptitler yüksek düzeyde belirlenmiştir. Peynir üretimi gerçekleştirilirken ideal proteolitik aktivite ve biyopeptit miktarını artırmak için ideal bakteri suşunun ve bakteri kombinasyonunun seçilmesi önemlidir.
... The molecular weight of α-lactalbumin from camel milk is 14.6 kDa, and it contains 123 amino acids which is similar to those in cow's milk, humans and goats. Peptides derived from milk proteins have been shown to perform various functions such as antioxidant activities, anticancer and antihypertensive (ACE) activities, opioid activities, mineral binding, growth stimulation and antimicrobial activities ;Meisel 2005;).Consequently, casein may play important biological functions after decomposition with different proteases. The enzymatic hydrolysis of casein produce specific peptides exert bioactivety which reduce the risk of heart disease, diabetes and cancer (Beg et al. 1985, Mohammad 1993, Farah 1996, Clare and Swaisgood 2000, Rival et al. 2001, Kappeler et al. 2003Aimutis 2004, Meisel, 2005Chen et al. (1998and Chen et al. (1998 The antioxidant properties of the bio-active peptides are attributed to their composition, structure and hydrophobicity as well as position of amino acid residue, and the molecular weight. ...
... Peptides derived from milk proteins have been shown to perform various functions such as antioxidant activities, anticancer and antihypertensive (ACE) activities, opioid activities, mineral binding, growth stimulation and antimicrobial activities ;Meisel 2005;).Consequently, casein may play important biological functions after decomposition with different proteases. The enzymatic hydrolysis of casein produce specific peptides exert bioactivety which reduce the risk of heart disease, diabetes and cancer (Beg et al. 1985, Mohammad 1993, Farah 1996, Clare and Swaisgood 2000, Rival et al. 2001, Kappeler et al. 2003Aimutis 2004, Meisel, 2005Chen et al. (1998and Chen et al. (1998 The antioxidant properties of the bio-active peptides are attributed to their composition, structure and hydrophobicity as well as position of amino acid residue, and the molecular weight. The bioactivity of peptides obtained from camel milk casein has not been extensively studied so far, so it needs a lot of research in the future. ...
... Lactoferrin, which comes from whey protein, is another type of immune peptide with antimicrobial activity (Mehta, 2015). Another group of bioactive peptides is the phosphopeptides, which carry minerals, mainly calcium, and they also have an anticarcinogenic effect (Meisel, 2005). ...
Animal-based foods such as meat, fish, egg, and milk, are the most important sources of protein with high biological value. But the shelf life of these products is very short due to the higher moisture content. Drying is widely used for the preservation of a large number of food materials because the dried products are more stable during storage. Conventional drying methods are energy-intensive techniques; therefore, there is a need to search for alternative energy-efficient drying techniques. Conductive hydro drying (CHD) is an innovative drying technique for the production of food powder with high-quality attributes and it has been used as an alternative to conventional drying techniques. The most important advantages of CHD are low drying cost, short drying time, and less product temperature during drying. This chapter highlights conductive hydro drying as an innovative drying technique for drying meat, fish, egg, and milk. Besides, providing a critical review of its effect on the different quality attributes of these products.
... The genetic variation of kappa casein involving the mature protein could be associated with other polymorphisms in the non-coding sequences (promoter, introns) which might be causative mutations for the expression differences between some alleles, as has already been found for the two main bovine kappa casein (CSN 3 ) alleles (Martin et al., 2002). The favourable effect of the kappa casein (CSN 3 ) B variant on milk protein and kappa casein (CSN 3 ) expression could be linked to these amino acid differences in the mature protein, possibly affecting both the biological properties of kappa casein and its biochemical interactions with the other casein fractions in the casein micelle Meisel, 2005). Kappa casein protein (only casein fraction that contains the sulphur amino acids cysteine and methionine), constitutes approximately 13% of milk casein. ...
A review of the results reported by different research workers has been compiled; with the aim to focus on various aspects encompassing the application of the important areas of research work on milk kappa casein. The major whey proteins in cow milk are alpha-lactalbumin and beta-lactoglobulin. Casein is a slow-digesting protein in contrast to whey protein that is rapid digesting. Milk Casein is of 3 or 4 types and each type has a similar structure but distinct molecules with different compositions, genetic variations, and functional properties. The main components of the cow milk casein complex are αs1 (CSN1S1), αs2 (CSN1S2), β (CSN2), and κ-caseins (CSN3) with each one of them occurring in two or more variants. Transgenic technologies could be used to alter milk composition in cows. Kappa-casein has been associated with differences in milk yield, composition and processing. Research work on casein has been attempted in different species (cow, buffalo, sheep, goat, horse, camel), yet it needs be extended to the remaining species and breeds of animals. The accurate and early identification of milk protein genotypes can have a direct impact on reviewing and developing dairy cattle breeding programs, to achieve the target of increasing production of milk and quality of its constituents on an economic footing. The review details the applied aspects of casein, classification and structure, polymorphism of kappa casein gene in different species of animals.
... Lactococcus lactis (Kunji et al., 1998;Pritchard & Coolbear, 1993) and Lactobacillus helveticus (Martin-Hernandez, 1994;Zevaco, 1988) have high proteolytic activity. The proteolytic systems of these bacteria were studied as microbial catalysts for the generation of bioactive peptides (Meisel, 2005;Kunji et al., 2009). Antimicrobial and antioxidant characteristics of peptides formed during casein degradation are described for L. helveticus and partially for Lactobacillus casei (de Palencia, 1997). ...
Much attention is paid to the study of biologically active peptides from milk caseins, which are usually obtained by partial hydrolysis by the proteolytic system of lactic acid bacteria. These peptides have a wide range of beneficial properties, including mineral binding, antidiabetic, satiating, immunomodulating, opioid, antimicrobial and antioxidant properties. In this work, we investigated the antimicrobial and antioxidant activity of peptides obtained during the hydrolysis of milk caseins by Enterococcus faecalis AN1 proteases. SDS PAAG electrophoretic analysis of peptide fractions after 8 hours of milk casein proteolysis showed that proteases of this strain cleave all casein fractions (αs1-, αs2 and β-casein). RP-HPLC profile elution revealed a large amount of small, medium and long cationic and anionic peptides. Some fractions of these peptides have antimicrobial activity against Listeria monocytogenes EGDe 107776, Bacillus cereus, Escherichia coli CCM 4517 and Aspergillus niger CCM 8189. Peptide fractions obtained during the hydrolysis of caseins possessed strong antioxidant activity and surpassed native casein by 4.5 times. These data stimulate further research in the field of biomedicine and food technology with the aim of developing new and effective preparations and products for maintaining the health and safety of consumers.
... The worldwide sales of peptide drugs were reached to US$ 70 billion in 2019 [3], which reveals a lot of attention has been paid to peptide-based drugs. Milk is a source of bioactive peptides which are inactively located within the parent protein sequences [4,5]. These peptides are released from parental protein sequences using hydrolysis and cause a variety of biological activities, including antiviral [6], opioid [7], antithrombotic [8], antihypertensive [9], and antioxidant [10,11]. ...
Today, breast cancer and infectious diseases are very worrying that led to a widespread effort by researchers to discover natural remedies with no side effects to fight them. In the present study, we isolated camel milk protein fractions, casein and whey proteins, and hydrolyzed them using pepsin, trypsin, and both enzymes. Screening of peptides with anti-breast cancer and antibacterial activity against pathogens was performed. Peptides derived from whey protein fraction with the use of both enzymes showed very good activity against MCF-7 breast cancer with cell viability of 7.13%. The separate use of trypsin and pepsin to digest whey protein fraction yielded peptides with high antibacterial activity against S. aureus (inhibition zone of 4.17 ± 0.30 and 4.23 ± 0.32 cm, respectively) and E. coli (inhibition zone of 4.03 ± 0.15 and 4.03 ± 0.05 cm, respectively). Notably, in order to identify the effective peptides in camel milk, its protein sequences were retrieved and enzymatically digested in silico. Peptides that showed both anticancer and antibacterial properties and the highest stability in intestinal conditions were selected for the next step. Molecular interaction analysis was performed on specific receptors associated with breast cancer and/or antibacterial activity using molecular docking. The results showed that P3 (WNHIKRYF) and P5 (WSVGH) peptides had low binding energy and inhibition constant so that they specifically occupied active sites of protein targets. Our results introduced two peptide-drug candidates and new natural food additive that can be delivered to further animal and clinical trials.
... PGPIPN, a hexapeptide derived from the 63-68 amino acid residue of bovine β-casein [181], reduced the resistance of ovarian cancer cells to cisplatin by affecting the HSF1/HSP70 signaling pathway. Specifically, PGPIPN affected the expression levels of HSF1, HSP70 and MDR1 genes. ...
Heat Shock Factor 1 (HSF1) is a master regulator of heat shock responsive signaling. In addition to playing critical roles in cellular heat shock response, emerging evidence suggests that HSF1 also regulates a non-heat shock responsive transcriptional network to handle metabolic, chemical, and genetic stress. The function of HSF1 in cellular transformation and cancer development has been extensively studied in recent years. Due to important roles for HSF1 for coping with various stressful cellular states, research on HSF1 has been very active. New functions and molecular mechanisms underlying these functions have been continuously discovered, providing new targets for novel cancer treatment strategies. In this article, we review the essential roles and mechanisms of HSF1 action in cancer cells, focusing more on recently discovered functions and their underlying mechanisms to reflect the new advances in cancer biology. In addition, we emphasize new advances with regard to HSF1 inhibitors for cancer drug development.
... Anticancer peptides are isolated from milk proteins (caseins), soy proteins (Lunasin) and many marine organisms (Kim et al., 2000Otani & Suzuki, 2003;Roy et al., 1999). Bioactive peptides may exert the protective effect through the mechanisms supporting cell viability and immune cell functions (Meisel, 2005). There are possibilities of applying enzymatic hydrolysis procedures for the production of novel anticancer peptides. ...
... BSA is not produced in the mammary gland, but appears in milk as a result of passive bloodstream leakage (Gupta and Prakash 2017). A few BSA derived peptides have been identified to possess biological activities, including serorphin and serokinin or albutensin A (Meisel 2005;Krissansen 2007). There is some evidence that proves the anti-cancer effects of BSA via reducing tumor growth by modulating the activity of autocrine growth regulating factors (Laursen, Briand, and Lykkesfeldt 1990;Teixeira et al. 2019). ...
Cancer prevalence is rising rapidly around the globe, contributing immensely to the burden on health systems, hence the search for more effective and selective treatments still remains enticing. Whey, as a natural source, has received extensive focus in recent years because of its intriguing applications to health benefits. Growing consumer appreciation of the nutraceutical effects of whey components makes them an attractive field within cancer research. Whey is a valuable source of superior-quality proteins, lactose, vitamins, and minerals that contribute to proper nutrition as well as help hamper illness and even complement certain disease-related therapy prognosis. As a result, industry leaders and dairy producers are devising new ways to valorize it. Great emphasis on cancer prevention and treatment has been given to whey protein (WP) by the scientific community. WP intake has been proven to induce anti-cancer effects in various in vitro and in vivo studies. Nutritionists and dietitians are now enormously endorsing the role of WP in the therapeutic field, notably for cancer cachexia management. However, human intervention studies with WP are in their infancy and remain to be established with different tumor entities to provide valid proof of its ability to act as a coadjuvant in cancer treatment.
... Micronutrient malnutrition, the so-called hidden hunger, effects more than half of the world's population; mainly women and pre-school children in developing countries (US FDA 2003). The clinical and epidemiological evidence show that minerals and vitamins play a significant role in the maintenance of optimal health and are limiting in diet (Meisel 2005). Vitamin B6 in conjunction with B12 plays an important role in protecting against cardiovascular disease. ...
The trillions of harmless microbes that are present in human gut are known as the gut microbiota. The consumption of food affects the composition of the gut microbiota, which leads to an imbalanced microbial population in the gut, a condition that is known as gut dysbiosis. The consumption of a diet that is high in fat and sugar can lead to development of obesity, type 2 diabetes mellitus, cardiovascular disease, and cognitive decline. The association between gut microbes and the occurrence of obesity is well established, and long-term consumption of a high-fat diet leads to cognitive decline. Obesity is strongly related to behavioral, environmental, and genetic factors. The gut microbiota contains ten times the total cells present in the human body. Gut dysbiosis is related to several diseases, such as type 2 diabetes mellitus, metabolic syndrome, obesity, nonalcoholic fatty acid syndrome, and cognitive decline. Diet has a direct role in the composition of the gut microbiota, and cognitive health in childhood and adulthood is significantly determined by the food intake. This chapter emphasizes the microbiota gut-brain axis and the role of diet in determination of cognitive functions.
... These compounds have low cytotoxicity compared to drugs used in traditional chemotherapy (Barras and Widmann 2011). Certain peptides obtained through the hydrolysis of whey protein have anticancer properties (Kimura, Sumiyoshi, and Kobayashi 2014), and they act as specific signals that can inhibit the viability of cancer cells (Figure 6), mainly through the rupture of the cytoplasmic membrane by the formation of pores and by induction of apoptosis (Meisel 2005;Papo and Shai 2005). ...
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.
... WPH is a source of bioactive peptides that are inactive in the intact protein but become active after hydrolysis. Depending on the amino acid content, sequences, and structures, the peptides generated can have different biological functions (Mann et al. 2019;Meisel 2005). The available information about the biological activities of hydrolysates/peptides derived from whey is abundant (Corrochano et al. 2018;Mann et al. 2019;Zhao and Ashaolu 2020). ...
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.
... This activity has been evaluated by using in vitro methods, such as the ABTS radical scavenging capacity, before being assessed in cellular systems or in vivo animal models [61][62][63]. Mechanisms proposed for the antioxidant activity of peptides include free radical scavenging and chelation of transition metals [64]; induction of antioxidant enzymes, such as catalase or superoxide dismutase [65]; induction of antioxidant molecules (e.g., glutathione), which protect cells from damage by reactive oxygen species [66,67]; and inhibition of oxidative enzymes, such as lipoxygenase, which catalyses oxidation of unsaturated fatty acids [14]. Antioxidant activity of peptides has been attributed to certain sequences of amino acids containing cysteine, methionine, lysine, histidine, tryptophan and tyrosine [68,69]. ...
The low molecular weight peptide composition of virgin olive oil (VOO) is mostly unknown. We aimed to investigate the composition of the endogenous peptides present in VOO, the protein sources from which those peptides originate and their biological activities. A water-soluble extract containing peptides was obtained from VOO. The peptides were separated by size-exclusion using fast protein liquid chromatography, and the low molecular weight fraction (1600-700 kDa) was analysed by nanoscale liquid chromatography Orbitrap coupled with tandem mass spectrometry and de novo sequencing. Nineteen new peptides were identified by Peaks database algorithm, using the available Olea europaea (cv. Farga) genome database. Eight new peptides were also identified by Peaks de novo sequencing. The protein sources of the peptides detected in the database by Peaks DB were identified by BLAST-P search. Seed storage proteins were among the most frequent sources of VOO peptides. BIOPEP software was used to predict the biological activities of peptides and to simulate (in silico) the proteolytic activity of digestive enzymes on the detected peptide sequences. A selection of synthetic peptides was obtained for investigation of their bioactivities. Peptides VCGEAFGKA, NALLCSNS, CPANGFY, CCYSVY and DCHYFL possessed strong ACE-inhibitory and antioxidant activities in vitro. Antioxidant peptides could play a role in VOO quality.
... Bovine milk Lys-Val-Leu-Pro-Val-P(Glu) Antihypertensive activity (10) N/A Antimicrobial activity (11) Cheddar cheeses N/A Antimicrobial, antioxidant, and antihypertensive activity (12) N/A Phosphopeptides (13) Casein hydrolysates Arg-Tyr-Lue-Gly-Tyr Antihypertensive activity (14) Comte cheese N/A Phosphopeptides The protein's foaming ability, on the other hand, reduced as its surface hydrophobicity dropped. ...
Bioactive peptides generated from food proteins have great potential as functional foods and nutraceuticals. Bioactive peptides possess several significant functions, such as antioxidative, anti-inflammatory, anticancer, antimicrobial, immunomodulatory, and antihypertensive effects in the living body. In recent years, numerous reports have been published describing bioactive peptides/hydrolysates produced from various food sources. Herein, we reviewed the bioactive peptides or protein hydrolysates found in the plant, animal, marine, and dairy products, as well as their by-products. This review also emphasizes the health benefits, bioactivities, and utilization of active peptides obtained from the mentioned sources. Their possible application in functional product development, feed, wound healing, pharmaceutical and cosmetic industries, and their use as food additives have all been investigated alongside considerations on their safety.
... According to prior research, the protein band of 14.2 kDa corresponds to a-lactalbumin (Lisak et al. 2013). Presence of lower molecular weight bands (10 kDa) in the SDS profile has increased the possibility of finding the bioactive peptides from fermented camel milk (Meisel 2005). A decrease in the concentration of a-lactalbumin (ALA) was observed SDS-PAGE gel electrophoresis. ...
Fermented camel milk provides many health benefits like antidiabetic activity, anti-hypertensive activity etc. Fermented camel milk contains IPP or VPP rich ACE inhibitory peptides. The aim of this study was to spot the novel Angiotensin I-Converting Enzyme inhibitory peptides liberated by the potent proteolytic Lactobacillus acidophilus NCDC-15 from camel milk (Indian breed). NCDC-15 had exhibited maximum PepX activity (0.655) and ACE-inhibitory activity (78.33%) at 12 and 48 h of incubation at 37 °C respectively. Proteolytic activity was measured using o-phthaldialdehyde method and observed maximum (0.976 OD) at 2% of inoculation for 12 h of incubation at 37 °C. Water soluble extracts derived from fermented camel milk were ultrafiltered through 3 kDa, 5 kDa and 10 kDa membrane filters from which 3 kDa permeates (48.01% peptides production & 49.46% ACE-inhibition) and 10 kDa permeates (55.04% peptides production & 42.40% ACE-inhibition) had shown maximum peptides production and ACE-inhibitory activity. Overall, 24 peptides were identified from the samples of 3 kDa permeates [6 fractions (K1, L1, M1, N1, O1 and P1)] and 10 permeates [5 fractions (S, T, U, V and W)]. Novel peptide (AIGPVADLHI) was matched with k-casein in AHTPDB database and other peptides were also found matched with α and β-caseins of camel milk.
Supplementary information:
The online version contains supplementary material available at 10.1007/s13197-022-05357-9.
... Many research scholars believe that some milk-derived bioactive peptides are a natural reversal agent to reverse cell resistance, but the research has just started and there are few reports on related research. Pro-Gly-Pro-Ile-Pro-Asn (PGPIPN) is a hexapeptide derived from the 63-68 amino acid residue of bovine β-casein [21]. We found in previous experiments that PGPIPN could effectively reduce inflammation and promote the immune of body, thereby reducing alcoholic liver injury [22,23]. ...
Ovarian cancer is the leading cause of death in gynecologic malignancies. Ovarian cancer as a metastatic malignant tumor is highly recurrent and prone to drug resistance. Bioactive peptides are an emerging area of biomedical research in reducing resistance of tumor cell to drugs. In this paper, we investigated the effects and mechanisms of bioactive hexapeptide (PGPIPN) derived in milk protein on the sensitivity of ovarian cancer cells to cis-dichlorodiammine platinum (DDP). Human ovarian cancer cell lines (SKOV3 and COC1), their DDP-resistant sublines (SKOV3/DDP and COC1/DDP) and human primary ovarian cancer cells were cultured in vitro under the combined treatment of DDP (close to IC50) and different concentrations of PGPIPN. The viabilities, apoptosis and cell cycle changes were respectively measured by WST-8 and flow cytometry. The mRNA and protein expression levels of HSF1, HSP70, MDR1, ERCC1 and β-actin gene were respectively assayed by RT-qPCR and western blotting. The results showed that PGPIPN significantly increased the sensitivity of human ovarian cancer cells to DDP in inhibiting viability and inducing apoptosis in vitro. But the effects in sensitive cells were lower than DDP-resistant cells. PGPIPN significantly changed the cell cycles in all human ovarian cancer cells, which leaded to a significant increase in the percentage of cells blocked at G2/M phase and decrease the percentage of cells at G1 phases in a dose-dependent manner. PGPIPN affected the expression levels of HSF1, HSP70, MDR1 and ERCC1 genes. Compared with cells in DDP treatment alone, the expression levels of HSF1 and HSP70 in human ovarian cancer cells treated with DDP and PGPIPN together significantly decreased in dose-dependent manner. PGPIPN significantly decreased MDR1 and ERCC1 of drug-resistant ovarian cancer cell lines and human primary ovarian cancer cell in a dose-dependent manner. Pifithrin-μ (PFTμ, HSP70 inhibitor) decreased or removed the effects of peptide in increasing the sensitivity of ovarian cancer cells to DDP. This suggests that PGPIPN enhanced the sensitivity of ovarian cancer cells to DDP partially via reducing the activity of HSF1/HSP70 signaling pathway, thus inducing cell apoptosis and decreasing repairment of DNA damage.
... Antihypertensive, opioid, antithrombotic, casein phosphopeptides, cytomodulatory, antimicrobial, mineral carrier and immunomodulatory peptides are important categories of bioactive peptides derived from milk proteins. [93][94][95][96][97] Meisel [98] illustrated that milk proteins contain some bioactive peptides, such as casomorphins, α-lactorphin, β-lactorphin, lactoferroxins, casoxins, casokinin, lactokinins, immunopeptides, lactoferricin, casoplatelins, and phosphopeptides. Exploring minor dairy species such as sheep, goats, camel, Mithun, mare, and the donkey has recently increased the growing interest in bioactive peptides among researchers. ...
Bioactive peptides (BPs) are specific protein fragments formed by amino acids joined by covalent bonds known as amide or peptide bonds that exert various beneficial effects on human bodies and ultimately influence health, reckoning on their structural properties and aminoalkanoic acid composition and sequences. These peptides can be obtained from plants, animals, microorganisms, and fermented food and may be consumed as nutraceuticals. Most BPs display one or more specific biofunctional features. BPs are the new generation of biologically active regulators; they can prevent oxidation and microbial decomposition in foods as well as improve the treatment of various diseases and disorders, thus increasing the quality of life. Also, the animal food proteins are currently considered as the crucial source of a variety of bioactive peptides and have gained special attention because they may probably influence many physiological responses along with maintenance of good health condition. This review focused on bioactive peptides as useful food preservatives and on reviewing their potential pharmaceutical role, due to their antioxidant and/or antimicrobial effects.
... Many studies have reviewed the production and properties of peptides from milk proteins (Clare & Swaisgood, 2000;Korhonen & Pihlanto, 2003;Meisel, 2005;Silva & Malcata, 2005;Korhonen & Pihlanto, 2006). Several bioactive peptides have good health effects on digestive, immune, cardiovascular and nervous systems (Korhonen & Pihlanto, 2006;Hernández-Ledesma et al., 2011). ...
Camel’s milk is an important part of staple diet in several parts of the world, particularly in the arid and semi-arid zones. Camel’s milk is rich in health-beneficial substances, such as bioactive peptides, lactoferrin, zinc, and mono and polyunsaturated fatty acids. These substances could help in the treatment of some important human diseases like tuberculosis, asthma, gastrointestinal diseases, and jaundice. Camel’s milk composition is more variable compared to cow’s milk. The effects of feed, breed, age, and lactation stage on milk composition are more significant in camel. Region and season significantly change the ratio of compounds in camel’s milk. Camel’s whey protein is not only composed of numerous soluble proteins, but also has indigenous proteases such as chymotrypsin A and cathepsin D. In addition to their high nutritional value, these whey proteins have unique characteristics, including physical, chemical, physiological, functional, and technological features that are useful in the food application. The hydrolysis of camel’s milk proteins leads to the formation of bioactive peptides, which affect major organ systems of the body and impart physiological functions to these systems. The camel’s milk has antioxidant, antimicrobial, angiotensin-I-converting enzyme (ACE)-inhibitory peptides, antidiabetic as well as anticholesterol activities.
... receptors, enzymes) on the luminal side of the intestinal tract. Opioid peptides are opioid receptor ligands which can modulate absorption processes(Meisel, 2005).Goat's milk is used in human medicine as therapy against different gastrointestinal problems, including vomiting and colic, and it may have beneficial effects on malabsorption disorders and inflammatory bowel diseases(Zenebe et al., 2014;Vaquil and Rathee, 2017). All these data indicate that the traditional use of ruminants' milk as a remedy to treat domestic animals with gastrointestinal problems such as meteorism or indigestion, or in the case of poisoning, is endorsed by actual pharmacological knowledge and biomedicine.Lanolin, also called wool wax or wool grease, is the unctuous secretion of the sebaceous glands of sheep which is deposited onto the wool fibres. ...
Ethnopharmacological relevance
This review documents the wide and varied repertoire of traditional practices and remedies based on the use of domestic animals in Spanish ethnoveterinary medicine (EVM) from the early 20th century to the present. Empirical practices, both ritual and magical, are recorded, and these EVM data are compared with those of other countries in the Mediterranean region and Latin America. The data collected here could form a scientific foundation for future inventories of local veterinary knowledge (LVK) and research addressing the discovery of new drugs for livestock and the validation of the effects.
Materials and methods
A qualitative systematic review of the most important databases in the fields of ethnobiology, ethnoveterinary medicine, folklore and ethnography was performed. Information and use-reports were obtained from more than 60 documentary sources.
Results
We recorded the use of nine domestic animal species and one hybrid (the mule) and a total of 171 empirical remedies based on the use of a single species. A wide diversity of body parts or derivative products were/are used. Fat was/is the most commonly used product, being used in 71 remedies (42%). These zootherapeutic resources were/are used to treat or prevent a total of 69 animal diseases or medical conditions, in particular dermatological, reproductive and digestive ailments, together with some infectious diseases. Sheep, cattle, goats and equines form the group of domestic animals in which the greatest number of useful species is employed. In addition, many remedies and practices of the magical-religious type are documented. In comparison with other culturally related areas, there is a greater parallelism in the animals and body parts and derivative products used, and the ailments treated.
Conclusions
Contemporary Spanish EVM practices amass a great richness of domestic animal-based remedies. A diversity of body parts or derivative products has been used, offering a cultural heritage that could be a fundamental step in the discovery of new and low-cost drugs for treating livestock and alternative materials for pharmaceutical purposes, and it can contribute to the creation of new strategies for the conservation of natural resources and management of endangered species. The usage of zootherapeutic products derived from wild animals can be replaced by the use of products isolated from domestic animals. Finally, this overview contributes to the inventory of some uses, traditional practices and rituals seriously threatened by the progressive loss of LVK.
... Es interesante señalar que la -caseína siendo la subunidad de mayor representatividad dentro de la micela de caseína (20) y por asociación del CS, ejerza efectos similares a éste en cuanto a proliferación e incluso diferenciación y expresión de citocinas. En este sentido, dado que es conocido que las caseínas presentan en su estructura péptidos bioactivos algunos de ellos con características opioides (22,23), sería interesante determinar si alguno de éstos péptidos es el responsable de la inducción de TNF- en las células 32D tratadas con -caseína. ...
Se ha mostrado que el caseinato de sodio y sus componentes (-caseína, -caseína y -caseína) inhiben la proliferación de la línea celular hematopoyética de ratón 32D cl3 e inducen su diferenciación hacia macrófagos. Se conoce que la α-caseína induce la producción de IL-1 y esta citocina inhibe la proliferación celular vía producción del factor de necrosis tumoral alfa (TNF-), pero se desconoce si el caseinato de sodio y las caseínas inducen la producción de TNF y éste es el responsable de la inhibición de inhiben la proliferación.
... Kazein ve peynir altı (whey) proteini gibi süt proteinleri, immünomodülatör peptidlerin öncüleri olarak tanımlanmışlardır (68). Mürin splenosit hücre kültüründe, whey proteinlerinin hidroliz sonrası kankavalin A ile muamele edildiklerinde IL-2 ve interferon gamma (IFN-gamma) düzeyinde artış görülmesi, asidik veya nötral peptid fraksiyonlarının splenosit proliferasyonunu uyarmasına bağlanmıştır (69). ...
... At present, milk proteins are considered the most important source of animal-based bioactive peptides. All these peptides have been extensively revised, so they will not be focused on within this revision [51][52][53][54][55][56][57]. ...
The call for health-promoting nutraceuticals and functional foods containing bioactive compounds is growing. Among the great diversity of functional phytochemicals, polyphenols and, more recently, bioactive peptides have stood out as functional compounds. The amount of an ingested nutrient able to reach the bloodstream and exert the biological activity is a critical factor, and is affected by several factors, such as food components and food processing. This can lead to unclaimed interactions and/or reactions between bioactive compounds, which is particularly important for these bioactive compounds, since some polyphenols are widely known for their ability to interact and/or precipitate proteins/peptides. This review focuses on this important topic, addressing how these interactions could affect molecules digestion, absorption, metabolism and (biological)function. At the end, it is evidenced that further research is needed to understand the true effect of polyphenol-bioactive peptide interactions on overall health outcomes.
... In vivo, encrypted peptides can be liberated during gastrointestinal digestion by enzymes such as trypsin or by microbial enzymes. In vitro, bioactive peptides can be released during food processing or ripening by microbial enzymes (e.g., Lactobacillus helveticus) [223][224][225][226]. These peptides are short sequences of approximately 2-20 amino acids [227] and, to be transported intact to the target site or organ, bioactive peptides must escape degradation during digestion. ...
Overweight and obesity are among the most prominent health problems in the modern world, mostly because they are either associated with or increase the risk of other diseases such as type 2 diabetes, hypertension, and/or cancer. Most professional organizations define overweight and obesity according to individual body-mass index (BMI, weight in kilograms divided by height squared in meters). Overweight is defined as individuals with BMI from 25 to 29, and obesity as individuals with BMI ≥30. Obesity is the result of genetic, behavioral, environmental, physiological, social, and cultural factors that result in energy imbalance and promote excessive fat deposition. Despite all the knowledge concerning the pathophysiology of obesity, which is considered a disease, none of the existing treatments alone or in combination can normalize blood glucose concentration and prevent debilitating complications from obesity. This review discusses some new perspectives for overweight and obesity treatments, including the use of the new orally active cannabinoid peptide Pep19, the advantage of which is the absence of undesired central nervous system effects usually experienced with other cannabinoids.
... Milk peptides also facilitate absorption of other nutrients in the gastro-intestinal tract, provide humoral immune responses and support intestinal development [12]. Besides, digestion or fermentation of milk proteins also produces a number of bioactive peptides, which contribute as well to the various functional properties of milk [13,14]. The major proteins in milk are far outnumbered by numerous other minor proteins which play important roles in a wide range of physiological activities including antioxidant activity, postnatal development of new-borns, maturation of the immune system, establishment of symbiotic microflora, and protection against various pathogens [15,16]. ...
Background:
Exploration of the bioactive components of bovine milk has gained global interest due to their potential applications in human nutrition and health promotion. Despite advances in proteomics profiling, limited studies have been carried out to fully characterize the bovine milk proteome. This study explored the milk proteome of Jersey and Kashmiri cattle at day 90 of lactation using high-resolution mass spectrometry based quantitative proteomics nano-scale LC-MS/Q-TOF technique. Data are available via ProteomeXchange with identifier PXD017412.
Results:
Proteins from whey were fractionated by precipitation into high and low abundant proteins. A total of 81 high-abundant and 99 low-abundant proteins were significantly differentially expressed between Kashmiri and Jersey cattle, clearly differentiating the two breeds at the proteome level. Among the top differentiating proteins, the Kashmiri cattle milk proteome was characterised by increased concentrations of immune-related proteins (apelin, acid glycoprotein, CD14 antigen), neonatal developmental protein (probetacellulin), xenobiotic metabolising enzyme (flavin monooxygenase 3 (FMO3), GLYCAM1 and HSP90AA1 (chaperone) while the Jersey milk proteome presented higher concentrations of enzyme modulators (SERPINA1, RAC1, serine peptidase inhibitor) and hydrolases (LTF, LPL, CYM, PNLIPRP2). Pathway analysis in Kashmiri cattle revealed enrichment of key pathways involved in the regulation of mammary gland development like Wnt signalling pathway, EGF receptor signalling pathway and FGF signalling pathway while a pathway (T-cell activation pathway) associated with immune system regulation was significantly enriched in Jersey cattle. Most importantly, the high-abundant FMO3 enzyme with an observed 17-fold higher expression in Kashmiri cattle milk seems to be a characteristic feature of the breed. The presence of this (FMO3) bioactive peptide/enzyme in Kashmiri cattle could be economically advantageous for milk products from Kashmiri cattle.
Conclusion:
In conclusion, this is the first study to provide insights not only into the milk proteome differences between Kashmiri and Jersey cattle but also provides potential directions for application of specific milk proteins from Kashmiri cattle in special milk preparations like infant formula.
... By that alteration bioactive peptides may show various activities such as opioid-like (narcotic), immune system regulator, antioxidant, antimicrobial, antithrombotic, hypocholesterolemic, cancer prevention, mineral binder, protective against heart attacks and antihypertensive effects. Important sources of various bioactive peptides include meat, milk and fish [5]. On the other hand, bioactive peptides of plant origin have recently attracted caution. ...
Bioactive peptides, which are naturally found in foods, have many physiological benefits during digestion that are obtained either by fermentation or by enzymatic hydrolysis. The biological action of these peptides can be registed as antimicrobial effect, lowering cholesterol, lowering blood pressure, antioxidant-antithrombotic effect, immunomodulator and opioid effects. Foods go through many processes until they become available to consumers. Frequently preferred processes in food technology such as heat treatment and fermentation affect bioactive peptide activity due to protein structure. Many proteins naturally present in foodstuffs show their physiological activity either directly or indirectly. Dietary protein was found to be a rich source of bioactive peptide. Foodborne bioactive peptides refer to peptides of herb and animal root that have regulatory duty in metabolism in usual and adequate nutrition. These peptides are passive in the protein series in which they are located and can be activated in three ways: (a) to hydrolysis by the nutritive enzymes, (b) hydrolysis by proteolytic microorganisms, (c) by the action of proteolytic enzymes released from microorganisms or herbs. In the fermentation process requires microorganism which is naturally present in raw material or added later starter culture. These microorganisms break down sugars and proteins to form peptides and free amino acids with different amino acid sequences. The degree of degradation of proteins depends on bacterial species and fermentation conditions. These peptides and amino acids produced from food by fermentation frequently alter the functional, sensory, biological and rheological properties of the fermented product. In this review, the creation of bioactive peptides and their various effects on health have been explored.
... Milk proteins are the main source of ACE inhibitory peptides. Most publications on ACE inhibitory and/or antihypertensive peptides have used peptides from cow milk (Korhonen and Pihlanto-Lepp¨al¨a, 2003;Gobbetti et al., 2004;Silva and Malcata, 2005;Meisel, 2005). However, in recent years, the sheep and goat milk proteins havebecome an important source of ACE inhibitory peptides. ...
... Milk contains a large amount of whey protein, which is also known as complete protein, the whey protein contains a wide range of essential amino acids and is rich in content, providing the proteins that the body needs [20]. Studies have shown that whey protein also plays an important role in wound healing [21,22]. The demand for protein during pregnancy increased more than usual, not only to meet the needs of embryonic development, but also have a very important role in pregnant women's heart, breast, uterus and other organs [23]. ...
Objective:
We study the risk factors that affect the formation of striae gravidarum in women in Jiangsu Province of China under current living habits.
Materials and methods:
This sample is based on 400 primiparas from obstetric of the Affiliated Hospital of Jiangnan University in Wuxi from February 2017 to October 2017. Among them, there are 200 pregnant women with striae gravidarum and 200 without striae gravidarum. Striae gravidarum predictors were selected such as age, height, pre-pregnancy BMI, postpartum BMI, daily sitting time, weight gain during pregnancy, fetal weight, and diet on maternal.
Results:
(1) The pregnant women who had striae gravidarum were generally lower in height than those who did not have striae gravidarum and had a higher BMI index than those who did not have striae gravidarum before and after childbirth. (2) In the pregnant women who have had striae gravidarum, the incidence of abdominal striae gravidarum in sedentary women is significantly lower than those in non-sedentary women, the incidence of striae gravidarum in legs is higher than those in non-sedentary women, and no significant difference in hip striae gravidarum. (3) In all pregnant women who have striae gravidarum, abdomen striae gravidarum tend to be lighter and leg striae gravidarum tends to be heavier in sedentary women, but no significant effect on the hip. (4) Regular consumption of honey, milk, trotters, freshwater fish, eggs, and tremella can reduce the incidence of striae gravidarum.
Conclusion:
The lifestyle and eating habits have a certain influence on the formation and severity of stretch marks.
In this thesis; the effects of heat treatment, starter culture, and plant coagulant on the peptide profile of goat cheese and the in vitro bioaccessibility of its bioactive peptides were investigated. For this purpose, raw and heat-treated goat milk was coagulated without adding starter culture and with adding starter culture. Coagulants originating from the abomasum of calf and Cynara cardunculus L. were used in milk coagulation. Cheeses produced were stored in refrigerator conditions for 90 days, and chemical, sensory, and microbiological properties, proteolysis levels, and peptide profiles were determined on the 1st, 30th, 60th, and 90th storage days. Cheeses were digested by in vitro gastrointestinal digestion simulation, and antioxidant and ACE inhibitory activities of small molecular weight peptide (< 3 kDa) fractions of samples were determined. There were no significant differences in chemical, microbiological, and sensory properties and proteolysis levels between cheeses produced using different coagulants, but the interaction of heat treatment and starter culture addition affected most of the cheese properties. Antioxidant activities determined on the 1st day of storage in terms of ABTS binding and in all storage days in terms of CUPRAC values were found to be higher in raw milk starter-free cheeses. In terms of ACE inhibitor activities, cheeses produced without using starter from heat-treated milk were found to have low values, but raw milk cheeses produced without the addition of starter culture, among cheeses stored for 30 days or longer, were found to have higher values. It was determined that there were increases and decreases in ACE inhibitory activities associated with the release and degradation of bioactive peptides during 90 days of storage in cheeses produced from raw milk.
Consequently, it was determined that heat treatment and starter culture were more effective on the determined properties of cheeses compared to the use of different coagulant enzymes. Accordingly, C. cardunculus L. protease could be used as an alternative to animal rennet in the production of goat cheese.
Metabolic syndrome (MS) is defined by the outcome of interconnected metabolic factors that directly increase the prevalence of obesity and other metabolic diseases. Currently, obesity is considered one of the most relevant topics of discussion because an epidemic heave of the incidence of obesity in both developing and underdeveloped countries has been reached. According to the World Obesity Atlas 2023 report, 38% of the world population are presently either obese or overweight. One of the causes of obesity is an imbalance of energy intake and energy expenditure, where nutritional imbalance due to consumption of high-calorie fast foods play a pivotal role. The dynamic interactions among different risk factors of obesity are highly complex; however, the underpinnings of hyperglycemia and dyslipidemia for obesity incidence are recognized. Fast foods, primarily composed of soluble carbohydrates, non-nutritive artificial sweeteners, saturated fats, and complexes of macronutrients (protein-carbohydrate, starch-lipid, starch-lipid-protein) provide high metabolic calories. Several experimental studies have pointed out that dairy proteins and peptides may modulate the activities of risk factors of obesity. To justify the results precisely, peptides from dairy milk proteins were synthesized under in vitro conditions and their contributions to biomarkers of obesity were assessed. Comprehensive information about the impact of proteins and peptides from dairy milks on fast food-induced obesity is presented in this narrative review article.
At different stages in history, milk has been referred to as both the “elixir of immortality” and “white poison.” This chapter offers a global history of fermented milk products, from early animal domestication in 8500 BCE to the role that yogurt cultures played in one of the greatest discoveries of the twenty-first century: CRISPR DNA sequences. It discusses the history of yogurt’s association with good health, a millennia-old belief among cultures across the world, as well as recent scientific explanations in support of such beliefs. It offers an overview of food safety challenges relating to milk preservation and distribution at the turn of the twentieth century, as well as a variety technologies developed to address these problems. Finally, it describes a number of social and environmental issues in the yogurt industry, from gendered marketing campaigns to acid whey pollution, offering insight into contemporary discourses of fermented milk as a “superfood.”KeywordsFermentationDairy products (Bulgarian yogurt, Greek yogurt, kefir, etc.)CRISPRProbiotics/live culturesCounterculture foodsHealth benefitsLongevityFood safetyFood marketing
Despite the key role of casein genes and their effect on quantitative traits and technological assets of milk, few studies manipulated it in camels, unlike other ruminants. Thus, this investigation was performed to lighten up the genetic polymorphism of CSN2 and CSN3 genes, in Maghrebi camels, via PCR-SSCP and DNA sequencing tools, by measuring the impacted milk composition traits. Sixty-eight blood samples were collected from Maghrebi camels in Mersa Matrouh, Egypt. Also, 68 milk samples were collected at different stages of the lactation period. Protein, fat, lactose, total solid, and ash were estimated in all milk samples by biochemical methods. The results of the PCR-SSCP and the sequence analysis showed two genotypes (CC and CA) in CSN2 gene with one SNP (41 T > G) for CC genotype and two SNPs (41 T > G and 462A > C) for CA genotype, as showed three genotypes (AA, AT, and TT) in CSN3 gene with two SNPs (42C > A and 346 T > A) for AA genotype, two SNPs (42C > A and 100 C > T) for TT genotype, and four SNPs (42C > A, 100C > T, 238 T > G, and 346 T > A) for AT genotype. Allele C of CSN2 gene affected milk fat only at the first day and the first seven days of lactation period, while allele T of CSN3 gene affected both the studied milk composition initiated from the first seven days to the end of the lactation period. The genetic discrimination of the understudied genes may be utilized as a valuable marker in the selection of superior animals, through the favorable alleles and genotypes to improve the camel milk composition.
Background
Secreted proteases are an important class of factors used by bacterial to modulate their extracellular environment through the cleavage of peptides and proteins. These proteases can range from broad, general proteolytic activity to high degrees of substrate specificity. They are often involved in interactions between bacteria and other species, even across kingdoms, allowing bacteria to survive and compete within their niche. As a result, many bacterial proteases are of clinical importance. The immune system is a common target for these enzymes, and bacteria have evolved ways to use these proteases to alter immune responses for their benefit. In addition to the wide variety of human proteins that can be targeted by bacterial proteases, bacteria also use these secreted factors to disrupt competing microbes, ranging from outright antimicrobial activity to disrupting processes like biofilm formation.
Objective
In this review, we address how bacterial proteases modulate host mechanisms of protection from infection and injury, including immune factors and cell barriers. We also discuss the contributions of bacterial proteases to microbe-microbe interactions, including antimicrobial and anti-biofilm dynamics.
Conclusion
Bacterial secreted proteases represent an incredibly diverse group of factors that bacteria use to shape and thrive in their microenvironment. Due to the range of activities and targets of these proteases, some have been noted for having potential as therapeutics. The vast array of bacterial proteases and their targets remains an expanding field of research, and this field has many important implications for human health.
In the last few years, developments in molecular biology, genomics, and proteomics have allowed remarkable progress in the understanding of milk protein structure and function, highlighting the extreme complexity and large variability (qualitative and quantitative) of the milk protein fraction, across, but also within, species. Meaningful examples taken in different species, including non-eutherian mammals, are discussed in this article to show how genomes and genetic polymorphisms may modulate the milk protein fraction by affecting different cellular processes, mainly at the posttranscriptional level (splicing of primary transcripts, posttranslational modifications), making milk a more complex biological fluid than previously assumed. However, the repertoire of minor milk proteins remains to be characterized more precisely in most species. Numerous substantiated or potential bioactive protein components have been found and many others still remain to be identified either as intact protein or as derived peptides, encrypted in the sequence of milk proteins. This is probably, with the characterization of milk-derived extracellular vesicles, the greatest challenges facing milk science in the next years to provide the food industry and consumers with the basis for health-promoting properties of these proteins and peptides, as well as milk-derived extracellular vesicles.
The proteins in milk have, for the most part, been well characterized with respect to their physical characteristics including their basic structures, amino acid sequence and quantity in lacteal secretions. Importantly, there is evolving knowledge of the role that these proteins play in both neonatal physiology and metabolism as well as the mammary gland itself. This article includes some discussion of the basic features of lesser-known minor milk proteins and their biological roles within normal neonatal development.
Napier hybrid is high yielding and perennial fodder crop admired by most of the dairy farmers. Sheath rot caused by Sclerotium rolfsii has been noticed on napier hybrid during past few years in Punjab state, India. Hence, to find out best management options and optimum nitrogen rate, experiments were conducted in 2018 and 2019 to determine the effect of different nitrogen levels (0, 50, 75 and 100 kg N ha−1), plant extracts and organic inputs on sheath rot development. In vitro studies showed that extracts of Aegle marmelos (92%), Nicotiana tabacum (89%), Murraya koenigii (86%) and organic inputs like panchgavya (100%), vermiwash (97%) and compost tea (96%) provided highest mycelial growth inhibition. In field trials, panchgavya provided least area under disease progress curve (AUDPC) values (689 and 492) and more than 80% reduction in sheath rot severity followed by A. marmelos and vermiwash with significant enhancement in green fodder yield by 42 and 46% in 2018 and 2019, respectively. The application of nitrogen rate 75 kg N ha−1 decreased the disease severity by 37% with 47% enhancement of green fodder yield in napier hybrid.
Sekundäre Pflanzenstoffe und ihre gesundheitsfördernden Eigenschaften sind in den letzten zwei Jahrzehnten vielfach ernährungsphysiologisch untersucht und spezifische positive Effek-te im humanen Organismus zum Teil sehr genau beschrieben worden. Zu den Carotinoiden zählend ist der sekundäre Pflanzenstoff Lutein insbesondere in der Prävention von ophthal-mologischen Erkrankungen in den Mittelpunkt der Forschung gerückt. Das ausschließlich von Pflanzen und einigen Algen synthetisierte Xanthophyll wird über die pflanzliche Nahrung insbesondere grünes Blattgemüse in den humanen Organismus aufgenommen. Dort akkumu-liert es bevorzugt im Makulapigment der Retina des menschlichen Auges und ist bedeutend im Prozess der Aufrechterhaltung der Funktionsfähigkeit der Photorezeptorzellen. Im Laufe des Alterns kann die Abnahme der Dichte des Makulapigments und der Abbau von Lutein beobachtet werden. Die dadurch eintretende Destabilisierung der Photorezeptorzellen im Zu-sammenhang mit einer veränderten Stoffwechsellage im alternden Organismus kann zur Aus-prägung der altersbedingten Makuladegeneration (AMD) führen. Die pathologische Sympto-matik der Augenerkrankung reicht vom Verlust der Sehschärfe bis hin zum irreversiblen Er-blinden. Da therapeutische Mittel ausschließlich ein Fortschreiten verhindern, bestehen hier Forschungsansätze präventive Maßnahmen zu finden. Die Supplementierung von luteinhalti-gen Präparaten bietet dabei einen Ansatzpunkt. Auf dem Markt finden sich bereits Nahrungs-ergänzungsmittel (NEM) mit Lutein in verschiedenen Applikationen. Limitierend ist dabei die Stabilität und Bioverfügbarkeit von Lutein, welches teilweise kostenintensiv und mit unbe-kannter Reinheit zu erwerben ist. Aus diesem Grund wäre die Verwendung von Luteinestern als die pflanzliche Speicherform des Luteins im Rahmen eines NEMs vorteilhaft. Neben ihrer natürlichen, höheren Stabilität sind Luteinester nachhaltig und kostengünstig einsetzbar. In dieser Arbeit wurden physikochemische und ernährungsphysiologisch relevante Aspekte in dem Produktentwicklungsprozess eines NEMs mit Luteinestern in einer kolloidalen Formulie-rung untersucht. Die bisher einzigartige Anwendung von Luteinestern in einem Mundspray sollte die Aufnahme des Wirkstoffes insbesondere für ältere Menschen erleichtern und verbes-sern. Unter Beachtung der Ergebnisse und der ernährungsphysiologischen Bewertung sollten u.a. Empfehlungen für die Rezepturzusammensetzungen einer Miniemulsion (Emulsion mit Partikelgrößen <1,0 µm) gegeben werden. Eine Einschätzung der Bioverfügbarkeit der Lutei-nester aus den entwickelten, kolloidalen Formulierungen konnte anhand von Studien zur Re-sorption- und Absorptionsverfügbarkeit in vitro ermöglicht werden. In physikalischen Untersuchungen wurden zunächst Basisbestandteile für die Formulierungen präzisiert. In ersten wirkstofffreien Musteremulsionen konnten ausgewählte Öle als Trägerpha-se sowie Emulgatoren und Löslichkeitsvermittler (Peptisatoren) hinsichtlich ihrer Eignung zur Bereitstellung einer Miniemulsion physikalisch geprüft werden. Die beste Stabilität und opti-male Eigenschaften einer Miniemulsion zeigten sich bei der Verwendung von MCT-Öl (engl. medium chain triglyceride) bzw. Rapsöl in der Trägerphase sowie des Emulga-tors Tween® 80 (Tween 80) allein oder in Kombination mit dem Molkenproteinhydrolysat Biozate® 1 (Biozate 1). Aus den physikalischen Untersuchungen der Musteremulsionen gingen die Präemulsionen als Prototypen hervor. Diese enthielten den Wirkstoff Lutein in verschiedenen Formen. So wur-den Präemulsionen mit Lutein, mit Luteinestern sowie mit Lutein und Luteinestern konzipiert, welche den Emulgator Tween 80 oder die Kombination mit Biozate 1 enthielten. Bei der Her-stellung der Präemulsionen führte die Anwendung der Emulgiertechniken Ultraschall mit an-schließender Hochdruckhomogenisation zu den gewünschten Miniemulsionen. Beide einge-setzten Emulgatoren boten optimale Stabilisierungseffekte. Anschließend erfolgte die phy-sikochemische Charakterisierung der Wirkstoffe. Insbesondere Luteinester aus Oleoresin er-wiesen sich hier als stabil gegenüber verschiedenen Lagerungsbedingungen. Ebenso konnte bei einer kurzzeitigen Behandlung der Wirkstoffe unter spezifischen mechanischen, thermischen, sauren und basischen Bedingungen eine Stabilität von Lutein und Luteinestern gezeigt wer-den. Die Zugabe von Biozate 1 bot dabei nur für Lutein einen zusätzlichen Schutz. Bei länge-rer physikochemischer Behandlung unterlagen die in den Miniemulsionen eingebrachten Wirk-stoffe moderaten Abbauvorgängen. Markant war deren Sensitivität gegenüber dem basischen Milieu. Im Rahmen der Rezepturentwicklung des NEMs war hier die Empfehlung, eine Mi-niemulsion mit einem leicht saurem pH-Milieu zum Schutz des Wirkstoffes durch kontrollierte Zugabe weiterer Inhaltstoffe zu gestalten. Im weiteren Entwicklungsprozess des NEMs wurden Fertigrezepturen mit dem Wirkstoff Luteinester aufgestellt. Die alleinige Anwendung des Emulgators Biozate 1 zeigte sich dabei als ungeeignet. Die weiterhin zur Verfügung stehenden Fertigrezepturen enthielten in der Öl-phase neben dem Wirkstoff das MCT-ÖL oder Rapsöl sowie -Tocopherol zur Stabilisierung. Die Wasserphase bestand aus dem Emulgator Tween 80 oder einer Kombination aus Tween 80 und Biozate 1. Zusatzstoffe waren zudem als mikrobiologischer Schutz Ascorbin-säure und Kaliumsorbat sowie für sensorische Effekte Xylitol und Orangenaroma. Die An-ordnung der Basisrezeptur und das angewendete Emulgierverfahren lieferten stabile Mi-niemulsionen. Weiterhin zeigten langfristige Lagerungsversuche mit den Fertigrezepturen bei 4°C, dass eine Aufrechterhaltung der geforderten Luteinestermenge im Produkt gewähr-leistet war. Analoge Untersuchungen an einem luteinhaltigen, marktgängigen Präparat bestä-tigten dagegen eine bereits bei kurzfristiger Lagerung auftretende Instabilität von Lutein. Abschließend wurde durch Resorptions- und Absorptionsstudien in vitro mit den Präemulsio-nen und Fertigrezepturen die Bioverfügbarkeit von Luteinestern geprüft. Nach Behandlung in einem etablierten in vitro Verdaumodell konnte eine geringfügige Resorptionsverfügbarkeit der Luteinester definiert werden. Limitiert war eine Micellarisierung des Wirkstoffes aus den konzipierten Formulierungen zu beobachten. Eine enzymatische Spaltung der Luteinester zu freiem Lutein wurde nur begrenzt festgestellt. Spezifität und Aktivität von entsprechenden hydrolytischen Lipasen sind als äußerst gering gegenüber Luteinestern zu bewerten. In sich anschließenden Zellkulturversuchen mit der Zelllinie Caco-2 wurden keine zytotoxischen Ef-fekte durch die relevanten Inhaltsstoffe in den Präemulsionen gezeigt. Dagegen konnten eine Sensibilität gegenüber den Fertigrezepturen beobachtet werden. Diese sollte im Zusammen-hang mit Irritationen der Schleimhäute des Magen-Darm-Traktes bedacht werden. Eine weni-ger komplexe Rezeptur könnte die beobachteten Einschränkungen möglicherweise minimieren. Abschließende Absorptionsstudien zeigten, dass grundsätzlich eine geringfügige Aufnahme von vorrangig Lutein, aber auch Luteinmonoestern in den Enterocyten aus Miniemulsionen erfolgen kann. Dabei hatte weder Tween 80 noch Biozate 1 einen förderlichen Einfluss auf die Absorptionsrate von Lutein oder Luteinestern. Die Metabolisierung der Wirkstoffe durch vorherigen in vitro-Verdau steigerte die zelluläre Aufnahme von Wirkstoffen aus Formulie-rungen mit Lutein und Luteinestern gleichermaßen. Die beobachtete Aufnahme von Lutein und Luteinmonoestern in den Enterocyten scheint über passive Diffusion zu erfolgen, wobei auch der aktive Transport nicht ausgeschlossen werden kann. Dagegen können Luteindiester aufgrund ihrer Molekülgröße nicht über den Weg der Micellarisierung und einfachen Diffusi-on in die Enterocyten gelangen. Ihre Aufnahme in die Dünndarmepithelzellen bedarf einer vorherigen hydrolytischen Spaltung durch spezifische Lipasen. Dieser Schritt limitiert wiede-rum die effektive Aufnahme der Luteinester in die Zellen bzw. stellt eine Einschränkung in ihrer Bioverfügbarkeit im Vergleich zu freiem Lutein dar. Zusammenfassend konnte für die physikochemisch stabilen Luteinester eine geringe Biover-fügbarkeit aus kolloidalen Formulierungen gezeigt werden. Dennoch ist die Verwendung als Wirkstoffquelle für den sekundären Pflanzenstoff Lutein in einem NEM zu empfehlen. Im Zusammenhang mit der Aufnahme von luteinreichen, pflanzlichen Lebensmitteln kann trotz der zu erwartenden geringen Bioverfügbarkeit der Luteinester aus dem NEM ein Beitrag zur Verbesserung des Luteinstatus erreicht werden. Entsprechende Publikationen zeigten eindeu-tige Korrelationen zwischen der Aufnahme von luteinesterhaltigen Präparaten und einem An-stieg der Luteinkonzentration im Serum bzw. der Makulapigmentdichte in vivo. Die geringfü-gig bessere Bioverfügbarkeit von freiem Lutein steht im kritischen Zusammenhang mit seiner Instabilität und Kostenintensität. Bilanzierend wurde im Rahmen dieser Arbeit das marktgän-gige Produkt Vita Culus® konzipiert. Im Ausblick sollten humane Interventionsstudien mit dem NEM die abschließende Bewertung der Bioverfügbarkeit von Luteinestern aus dem Prä-parat möglich machen.
Three scallop protein hydrolysates (SPH) were obtained by enzymatic hydrolysis of scallop meal by Pepsin, Dispase and Alcalase, respectively. The antioxidant activities of the SPHs were characterized for their free radical scavenging activities through 1,1-diphenyl-2-picrylhydrazyl (DPPH)/hydroxyl/2,2′ azino-bis-3-(ethylbenzthiazoline-6-sulphonic acid) (ABTS) assays, showing at least 60% radicals scavenging activities in samples (10 mg/mL). Moreover, the Alcalase-hydrolyzed SPH (ASPH) was shown to have the highest free radical scavenging activity determined by Electron Spin Resonance (ESR), due to the high proportion of antioxidant amino acids (35.25%) and better solubility. In addition, the ASPH also exhibited promising inhibitory effects (30–40%) against lipid oxidation in emulsifying system and excellent emulsifying and foaming properties. In vitro, the ASPH exhibited protective effects (nearly 20%) against H2O2-induced cytotoxicity probably due to the inhibition of mitochondria-associated generation of reactive oxygen species (ROS). The ASPH may potentially serve as a high-valued scallop-based food additive with great health benefits.
The bioactive peptides released from cheeses have important physiological functions such as angiotensinogen converting enzyme (ACE)‐ inhibition, anti‐ oxidant, anti‐ thrombotic, anti‐ microbial, anti‐ cancer, and anti‐ inflammatory. These bioactive peptides can be produced from precursor milk protein during processing, enzymatic hydrolysis, microbial fermentation and gastrointestinal digestion. 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.
BACKGROUND
An extreme reduction of the crude protein (CP) level in diets, even balanced with amino acids (AAs), is detrimental for intestinal nitrogen (N) metabolism and the growth of pigs. This study investigated the effects of casein hydrolysate supplementation in low‐CP diets on growth performance, N balance, and intestinal N supply for pigs. A total of 24 barrows were randomly assigned to one of three dietary treatments of 160 g kg⁻¹ CP (control), 130 g kg⁻¹ CP (LAA), and 130 g kg⁻¹ CP plus casein hydrolysate (LCH) for 28 days.
RESULTS
The LCH group had a higher average daily feed intake (ADFI) and average daily gain (ADG) than the LAA group, and a higher ADG than the control (P < 0.05). Compared with the control, both the LAA and LCH decreased N intake, serum urea N, fecal N, and N excretion, and increased apparent N availability, with LCH having higher N intake and N retention than LAA group (P < 0.05). Compared with LAA, LCH increased ileal fluxes of CP and AA (P < 0.05), and with values similar to those of the control. However, ileal flows of CP and AA were similar between LCH and LAA, both of which were lower than those in the control (P < 0.05).
CONCLUSION
Using protein hydrolysate to replace some crystalline AAs in low‐CP diets increased feed intake, N retention and ADG without affecting N utilization. These findings point to the important impact of protein hydrolysate supplementation on improving growth for pigs fed low‐CP diets. © 2019 Society of Chemical Industry
Angiotensin I–converting enzyme (ACE) catalyzes the conversion of angiotensin I to vasoconstrictor angiotensin II, and also inactivates the antihypertensive vasodilator bradykinin. Inhibition of ACE mainly results in an overall antihypertensive effect. Peptides derived from food proteins can have ACE inhibiting properties. This article reviews the ACE inhibitory peptides derived from different food proteins. Some of the ACE inhibitory peptides exhibit significant antihypertensive effects. However, the inhibitory potencies of these peptides on ACE activity do not always correlate with their antihypertensive activities. Some peptides with high inhibitory activity on this enzyme in vitro have no blood pressure lowering effects, whereas some peptides with low inhibitory activity on this enzyme in vitro have such effects. The possible mechanisms for this conflicting phenomenon between inhibitory activity and antihypertensive effect, the structure–activity relationships, and the potential use prospect of these peptides in the development of a novel functional food for preventing hypertension as well as therapeutic purposes, are also discussed.
Oral delivery of peptide, protein and vaccine biotechnology products remains the major challenge in drug delivery technology. In the main, these agents are administered to patients by injection, infusion or by subcutaneous implants. Oral delivery of intact peptide-based products is attractive because it offers improved convenience and patient compliance, and this will result in reduced overall healthcare costs. Taking into account the intestinal site of absorption and the physico-chemical properties of the agent, these labile compounds can be successfully formulated for oral delivery using intestinal-protective-, targeting- and epithelial-permeating approaches. Some of the more innovative current technologies are reviewed for these classes of biotech products.
Caseinophosphopeptides (CPPs) are phosphorylated casein-derived peptides which possess the ability to bind and solubilise minerals, such as Ca2+. Consumption of high concentrations of Ca2+ in early life contributes to the development of maximal bone density, which in turn can prevent osteoporosis in later life. Furthermore, a recent report has shown a positive correlation between Ca2+ intake and the prevention of hypertension. The high bioavailability of Ca2+ from milk and dairy products has, in part, been attributed to the production of CPPs which have different levels of phosphorylation and are produced in vivo following digestion of αs1-,αs2- and β-casein by the action of gastrointestinal proteinases. CPPs which appear to be resistant to extensive proteolytic degradation, accumulate in the distal small intestine where they are purported to play a role in enhancing the passive absorption of Ca2+ and other trace elements. CPPs have also been produced in vitro using a range of commercially available proteinases of pancreatic origin. Several CPP enrichment procedures from casein hydrolysates have been reported, generally involving Ca2+ induced aggregation followed by ultrafiltration. These CPP enriched preparations have been used to characterise their interaction with Ca2+ and trace elements and to determine their effect on the bioavailability of dietary Ca2+ during animal and human feeding trials. There are conflicting reports, arising from the results of animal feeding studies, on the effectiveness of CPPs in enhancing Ca2+ bioavailability. However, a recent human feeding trial reported improved Ca2+ and Zn2+ absorption following CPP incorporation into a rice-based infant food. In vitro produced CPPs may also find application in the prevention and treatment of dental calculus. This review summarises the production, characterisation and potential applications of CPPs.
Proteins and peptides containing clusters of phosphoseryl residues have been shown to stabilize amorphous calcium phosphate in solution, and have been implicated in the regulation of biomineralisation processes. Casein phosphopeptides (CPP) containing the cluster sequence -Ser(P)-Ser(P)-Ser(P)-Glu-Glu- have been demonstrated to significantly reduce the level of dental caries (tooth decay) in animal and human experiments and also to repair early stages of decay. Through their multiple phosphoseryl residues the peptides bind to forming nanoclusters of amorphous calcium phosphate (ACP) in metastable solution, preventing their growth to the critical size required for nucleation and phase transformation. Conformational and binding studies have shown that all the phosphoseryl residues are important in interaction with ACP. The CPP localise ACP at the tooth surface providing a reservoir of calcium and phosphate ions thereby helping to maintain a state of supersaturation with respect to tooth enamel. The CPP-ACP, unlike fluoride, can be added to sugar-containing foods as well as oral care products for the control of dental caries.
Dental caries (tooth decay) is the localised destruction of tooth tissue initiated by specific dental plaque bacteria that ferment dietary sugar to organic acids, Even though in most developed countries the prevalence of dental caries has decreased through the use of fluorides, the disease remains a major public health problem. A substantial volume of literature now exists demonstrating an anticariogenic effect of dairy products [milk, milk concentrates, powders and cheeses] in laboratory, animal and human in situ caries models. This anticariogenic effect has been attributed to the multiphosphoseryl-containing sequences of casein and their ability to stabilise calcium phosphate. These sequences can be released enzymically as casein phosphopeptides (CPP), which stabilise amorphous calcium phosphate (ACP) in solution by the formation of CPP-ACP nanocomplexes. The CPP-ACP localise at the tooth surface and prevent demineralisation and promote remineralisation of enamel subsurface lesions. CPP-ACP is now being used commercially as an ingredient (Recaldent™) in oral care products.
DNA-synthesis stimulatory activity was found in a tryptic hydrolysate of bovine β-caseins using BALB/c3T3 cells, and an active peptide was identified to be the fragment Ala[177] to Arg[183](β-CN(fl77 ˜ 183)). The activity of this casein fragment was confirmed using a synthetic peptide of β-CN(fl77 ˜ 183). © 1989, by the Japan Society for Bioscience, Biotechnology, and Agrochemistry.
An extract of autologous Lactobacillus casei cell lysate (LEx) is known to lower the blood pressure of spontaneously hypertensive rats (SHR). To determine the effects of LEx in humans, we enrolled twenty-eight patients with an average age of seventy-one years and with an average systolic blood pressure/diastolic blood pressure of 164/96mmHg in a 2-month, double-blind, placebo-controlled study. Four hundred milligrams of LEx or placebo powder enclosed in white capsules was given twice a day for 2 months. Decreases in systolic blood pressure (p<0.01), diastolic blood pressure (p<0.05), and heart rate (p<0.05) were observed in the LEx-treated group when compared with the baseline. As to the blood plasma component, both total cholesterol and fasting plasma glucose were reduced (p<0.05) in the LEx-treated group. These findings support the role of LEx in the treatment of hypertension with beneficial effects on glucose and lipid metabolism.
The effect on serum and intestinal IgG or IgA production of a dietary casein phosphopeptide preparation, CPP-III, mainly consisting of residues 132 of bovine αs2-casein and residues 128 of bovine β-casein, was investigated in mice. No significant difference was seen in body weight gained between mice fed a CPP-III-added diet (a mixture of 0.1 to 1.0 g CPP-III and 24.9 to 24.0 g ovalbumin as protein sources in 100 g diet) and mice fed a control diet (25.0 g ovalbumin in 100 g diet). Mice fed CPP-III-added diets exhibited a similar serum IgG response towards β-lactoglobulin injected peritoneally and ovalbumin ingested orally to those fed the control diet. In contrast, the level of serum IgA towards the proteins showed a rising tendency in mice fed CPP-III-added diets compared with those fed the control diet. The difference between the control diet group and CPP-III-added diet groups was often statistically significant. Moreover, the intestinal antigen-specific IgA and total IgA in some mice fed the CPP-III-added diet were significantly higher than those fed the control diet. The present results suggest that oral use of the casein phosphopeptide is beneficial to the enhancement of mucosal immunity.
Milk whey and casein proteins were fermented with different lactic acid starters and digestive enzymes. ACE-inhibition activity was observed only after the digestion of proteins with pepsin and trypsin. Whey proteins resulted in 35–61% inhibition and caseins 86% inhibition under the applied conditions. The hydrolysates having inhibitory activity were fractionated by size exclusion and reversed phase chromatography. Several ACE-inhibitory peptides were purified and identified by amino acid and MS-analysis. The identified peptides were α-la f105–110, β-lg f9–14, f15–20, αs1-cn f142–147, f157–164, f194–199 and β-cn f108–113, f177–183 and 193–198. Among whey hydrolysates peptides with small molecular weight (
In the present study, the effects of orally administered β-casomorphins (β-CM) and met-enkephalin on postprandial plasma somatostatin-like immunoreactivity (SLI) were assessed in conscious dogs. The intragastric instillation of a liver extract-sucrose test meal containing 12 mg β-CM or 10 mg met-enkephalin, respectively, augmented the postprandial rise of peripheral vein plasma SLI levels significantly. This effect was inhibited by the additional administration of the specific opiate-receptor antagonist, naloxone. When liver extract-sucrose was dissolved in fresh bovine milk the increase of plasma SLI levels was significantly greater than liver extract-sucrose dissolved in water. This milk-induced augmentation of SLI levels was also reduced by naloxone. Since these opiate-active compounds have an influence upon insulin release when given iv, the effect of β-CM-7, β-CM-5, β-CM-4, β-CM-4-amide, and met-enkephalin on SLI levels was assessed during their iv infusion at a rate of 1 nmol/kg.h during an iv background infusion of a glucose-amino acid mixture. The infusion of β-CM-5 elicited a stimulation of peripheral vein SLI levels, whereas the infusion of met-enkephalin resulted in a significant decrease of SLI levels. β-CM-7, β-CM-4, and β-CM-4-amide had no effect on plasma SLI levels at the dose employed. The present data demonstrate that in dogs the ingestion of opiate-active peptide stimulates postprandial SLI release, indicating that nutrient-contained opiate-active material (exorphins) might participate in the regulation of postprandial gastrointestinal endocrine function.
Bioactive peptides derived from the tryptic digestion of casein, known as caseinophosphopeptides (CPP), possess physicochemical properties that enable the chelation of various bi- and trivalent minerals, thereby enhancing mineral solubility in the lower small intestine. The significance of the interaction between CPP and calcium ions, in particular, for enhancing calcium absorption is presently a controversial issue due to the variations in the methodologies used to assess calcium biovailability.
The significance and developments in the application of the principal exogenous enzymes, rennets, lipases, lysozyme, catalase, glucose oxidase and β-galactosidase, used in cheese manufacture and ripening are discussed. Some indigenous milk enzymes, notably plasmin, lipoprotein lipase, acid phosphatase and xanthine oxidase, may also be significant in cheese ripening.
Casein and other milk proteins in maternal colostrum and milk, the earliest food of the newborn, should not only be considered as a nutritional supply but also as a source of biologically active peptides. Some of them isolated from casein and lactotransferrin were active on platelet function. They inhibited both aggregation of ADP-treated platelets and binding of [125I] fibrinogen to ADP-treated platelets. Their behaviour was compared to that of fibrinogen peptides possessing similar effects: once more similarities between the milk and blood-clotting phenomena could be observed.
The broad similarity between the milk clotting and blood clotting processes has been apparent for many years. Sequence homologies between fibrinogen and milk proteins, and similarities between the actions of the blood-clotting enzyme thrombin and the milk-clotting enzyme chymosin may explain the basis of the parallels between the two processes.
Tryptic hydrolysis of caseinomacropeptide (CMP: C-terminal part of k-Casein) was used as a model in membrane reactor to study continuous production and isolation of bioactive peptides from milk proteins. Compared to the batch reactor, productivity of the proposed continuous process was 3 times higher after 3.5 hours of hydrolysis, but only 50% of the substrate is converted at steady state of the system. As shown by reverse-phase HPLC analysis, a good selectivity of the ultrafiltration membrane to various products was also obtained.
Caseinphosphopeptide in a dose of 87.5 mg was administered to 35 normal post-menopausal women as a part of a standard test
meal containing a calcium load of 250 mg. Absorption of calcium was tested both with and without caseinphosphopeptide, using
an intrinsic45Ca label in the calcium source. The mean quotient of absorption with/without caseinphosphopeptide was greater than 1.0, but
nonsignificantly so. However, when analysis was confined to women with low absorption values, caseinphosphopeptide administration
was associated with significantly better absorption of co-ingested calcium. Those findings suggest that caseinphosphopeptide
supplementation is particularly useful, for persons with low basal absorptive performance.
Enzymatic hydrolysates of bovine β-lactoglobulin (β-Lg), α-lactalbumin (α-La) and whey protein concentrate (WPC) were analysed for their angiotensin-I-converting enzyme (ACE) inhibitory activity. The unhydrolysed substrates gave very low ACE inhibitory indices, i.e. < 10%. Hydrolysis of the whey proteins by pepsin, trypsin, chymotrypsin and the commercially available enzyme preparations, Corolase PP and PTN 3.0S, resulted in high ACE inhibition indices, i.e. 73–90%. Hydrolysates generated with elastase displayed relatively low ACE inhibitory activity. The order of trypsin and pepsin addition during the hydrolysis of α-La and β-Lg did not appear to affect the ACE inhibitory activity of the resulting hydrolysate. Preliminary studies indicated that ultrafiltration through 3 and 1 kDa molecular mass cut-off membranes may be exploited to enrich for ACE inhibitory peptides. The ACE IC50 inhibition values obtained for ultrafiltered tryptic digests of β-Lg and WPC ranged from 130–201 mg L−1. The potential application of whey protein hydrolysates as nutraceuticals in the prevention of hypertension is discussed.
Bovine skimmed milk digested with cell-free extract of the yeast Saccharomyces cerevisiae was found to exhibit proliferation inhibition activity towards human leukemia (HL-60) cells. The optimum pH for digestion of skimmed milk and production of the proliferation inhibition factor was pH 4.8. Nondigested skimmed milk exhibited little suppressive effect on the proliferation of HL-60 cells. An active enzyme involved in the production of cell proliferation inhibitory materials from skimmed milk was purified from the cell-free extract of S. cerevisiae by a series of column chromatographies: DEAE-Sephacel, d-tryptophan methyl ester-Sepharose 4B, Hiload Superdex G-200 and HPLC Mono Q. The homogeneous purified enzyme and exhibited a molecular mass of 33 kDa in sodium dodeceyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and was identified as protease B by N-terminal amino acid sequence analysis. Bovine skimmed milk digested with purified protease B was found to inhibit proliferation activity of HL-60 cells most strongly when digestion was conducted at pH 4.8. The cell proliferation inhibition activity induced by digested skimmed milk was shown to be due to the induction of apoptosis, demonstrated by the formation of apoptotic bodies and fragmentation of DNA in treated cells. The proliferation inhibition factors produced were recovered in the soluble fraction of 92% ethanol, suggesting that the factors were hydrophilic low molecular mass substances derived from skimmed milk.
Milk protein-derived bioactive peptides include a variety of substances which are potential modulators of various regulatory processes in the body; many peptides reveal multifunctional bioactivities. Opioid peptides are opioid receptor ligands with agonistic or antagonistic activities. Angiotensin converting enzyme (ACE)-inhibitory peptides can exert an antihypertensive effect. Immunomodulating casein peptides stimulate proliferation of human lymphocytes and phagocytic activities of macrophages. Antimicrobial peptides kill sensitive microorganisms. Antithrombotic peptides inhibit fibrinogen binding to a specific receptor region on the platelet surface and also inhibit aggregation of platelets. Caseinophosphopeptides can form soluble organophosphate salts and may function as carriers for different minerals, especially calcium. In relation to their mode of action, bioactive peptides may reach target sites (e.g., receptors and enzymes) at the luminal side of the intestinal tract or, after absorption, in peripheral organs. Milk-derived peptides can be produced on an industrial scale and as a consequence these peptides have already been considered for application both as dietary supplements in ‘functional foods’ and as drugs. Hence, these peptides are claimed to be health enhancing nutraceuticals for food and pharmaceutical preparations.
Angiotensin-converting enzyme (ACE) acts in blood pressure regulation, converting angiotensin I to the potent vasoconstrictor angiotensin II and inactivating the vasodilator bradykinin to raise blood pressure. Various synthetic ACE inhibitors are currently in use as antihypertensive agents. Recently, ACE-inhibitory peptides have been isolated from enzymatic digests of food proteins. The possible roles of these food-derived ACE inhibitors are discussed.
Measurement of electrophoretic mobilities of bovine casein phosphopeptides (αs1-CN(59–79), αs1-CN(43–58), β-CN(1–25), and β-CN(33–48)) and their dephosphorylated analogues at different calcium concentrations enabled the calculation of calcium-binding constants in the range of pH 5–8. Binding constants showed a maximum at pH 7 and were in the range 0.1–0.5 mM−1. The decrease at pH 8 might be attributed to the presence of carbon dioxide, leading to competitive binding of calcium ions. Phosphorylated peptides exhibited higher binding constants than their dephosphorylated analogues.
This review deals with milk derived peptides related to hypertension reduction, especially those from Calpis sour milk fermented by a starter containing Lactobacillus helveticus and Saccaharomyces cerevisiae. The inhibitory activity of angiotensin-I-converting enzyme (ACE) in milk increased during fermentation with the sour milk starter. Inhibitors were purified and identified as Val–Pro–Pro and Ile–Pro–Pro. These amino acid sequences are found in the primary structure of β-casein and κ-casein. Administration of sour milk or the chemically-synthesized tripeptides to spontaneously hypertensive rats resulted in similar reductions in blood pressure. The tripeptides were found in the aorta of spontaneously hypertensive rats, after oral administration of the sour milk. A clinical study demonstrated that the blood pressure of hypertensive human subjects was significantly reduced following daily ingestion of 95 mL of the sour milk for two months.
A casein polypeptidic fraction, obtained from a pepsin-chymosin digestion of caseins, showed a mitogenic effect on primed lymph node (LN) cells and unprimed spleen cells of rats. A biologically active C-terminal sequence of bovine beta-casein (residues 192-209) was characterized. The corresponding synthetic peptide had a stimulatory effect on primed LN cells but failed to enhance proliferation of spleen cells. We prepared two chymosin digests (PA and PB) of bovine beta-casein which contained, respectively, 80% and 95% of the sequence including residues 193-209. They induced a significant proliferative response in both LN and spleen cells. It is therefore possible that other active peptides in the PA preparation may be involved in mitogenic activity.
The multiple Ser(P)-containing peptides, H-Ser(P)-Ser(P)-Ser(P)-Glu-Glu-NHMe.TFA, H-Asp-Ser(P)-Ser(P)-Glu-Glu-NHMe.TFA and H-Glu-Ser(P)-Ser(P)-Glu-Glu-NHMe.TFA were prepared by the use of Boc-Ser(PO3Ph2)-OH in the Boc mode of solution phase peptide synthesis followed by platinum-mediated hydrogenolytic de-protection of the Ser(PO3Ph2)-containing peptides. The protected peptides were assembled using the mixed anhydride coupling methods with 40% TFA/CH2Cl2 used for removal of the Boc group from intermediate Boc-protected peptides.
Phosphopeptides derived from casein may function as carriers for calcium and trace elements. In regard to such specific nutritive effects, the heat-induced changes in tryptic phosphopeptides liberated from bovine sodium caseinate as a model system were investigated. Both microwave and oven heating resulted in a marked loss of peptide-bound phosphorous (dephosphorylation) and a decrease of casein-phosphopeptides in the soluble part of the tryptic hydrolysate. It is concluded that hydrolysis of phosphoseryl to seryl residues was the prevailing degradation step to soluble proteolytic products, whereas lysinoalanyl-casein is claimed to be present almost exclusively in the pH 4.6-insoluble part of the tryptic digest.
There are 14 unconfounded randomised trials of antihypertensive drugs (chiefly diuretics or beta-blockers): total 37,000 individuals, mean treatment duration 5 years, mean diastolic blood pressure (DBP) difference 5-6 mm Hg. In prospective observational studies, a long-term difference of 5-6 mm Hg in usual DBP is associated with about 35-40% less stroke and 20-25% less coronary heart disease (CHD). For those dying in the trials, the DBP difference had persisted only 2-3 years, yet an overview showed that vascular mortality was significantly reduced (2p less than 0.0002); non-vascular mortality appeared unchanged. Stroke was reduced by 42% SD 6 (95% confidence interval 35-50%; 289 vs 484 events, 2p less than 0.0001), suggesting that virtually all the epidemiologically expected stroke reduction appears rapidly. CHD was reduced by 14% SD 5 (95% CI 4-22%; 671 vs 771 events, 2p less than 0.01), suggesting that just over half the epidemiologically expected CHD reduction appears rapidly. Although this significant CHD reduction could well be worthwhile, its size remains indefinite for most circumstances (though beta-blockers after myocardial infarction are of substantial benefit). At present, therefore, a sufficiently high risk of stroke (perhaps because of age, blood pressure, or, in particular, history of cerebrovascular disease) may be the clearest indication for antihypertensive treatment.
The associations of diastolic blood pressure (DBP) with stroke and with coronary heart disease (CHD) were investigated in nine major prospective observational studies: total 420,000 individuals, 843 strokes, and 4856 CHD events, 6-25 (mean 10) years of follow-up. The combined results demonstrate positive, continuous, and apparently independent associations, with no significant heterogeneity of effect among different studies. Within the range of DBP studied (about 70-110 mm Hg), there was no evidence of any "threshold" below which lower levels of DBP were not associated with lower risks of stroke and of CHD. Previous analyses have described the uncorrected associations of DBP measured just at "baseline" with subsequent disease rates. But, because of the diluting effects of random fluctuations in DBP, these substantially underestimate the true associations of the usual DBP (ie, an individual's long-term average DBP) with disease. After correction for this "regression dilution" bias, prolonged differences in usual DBP of 5, 7.5, and 10 mm Hg were respectively associated with at least 34%, 46%, and 56% less stroke and at least 21%, 29%, and 37% less CHD. These associations are about 60% greater than in previous uncorrected analyses. (This regression dilution bias is quite general, so analogous corrections to the relations of cholesterol to CHD or of various other risk factors to CHD or to other diseases would likewise increase their estimated strengths.) The DBP results suggest that for the large majority of individuals, whether conventionally "hypertensive" or "normotensive", a lower blood pressure should eventually confer a lower risk of vascular disease.
HIV infection results in the destruction of the thymus-dependent cellular immune system and death due to opportunistic infection and malignancy. Immunosuppressive influences (other sexually or blood-transmitted viruses, HIV-derived peptides, semen, poor nutrition, drugs, etc.) favor the progression of the disease. Although immunorestorative agents may be expected to delay progression of the disease, John Hadden argues that no agent has yet proven useful in reversing the immunodeficiency in full-blown AIDS. However, two thymomimetic drugs, isoprinosine and diethyldithiocarbamate, inhibit the development of infections in patients with pre-AIDS in large multicenter trials, and preliminary data from trials with two thymomimetic peptides, thymopentin and ImReg-1, in pre-AIDS patients are encouraging.
The first part of the present review is focused on structural aspects concerning the so far studied casein fractions of various origins: they are compared to the four classical major bovine caseins (σsl-, σs2- β- and κ). The calcium-sensitive casein fractions are always phosphorylated whereas κ-caseins are glycosylated. The study of the casein genes showed that the calcium-sensitive caseins diverged from a common ancestral gene and during the evolution, intergenic and intragenic duplications occurred. The considerable conservation of the phosphorylation sites emphasizes the importance of phosphorylated residues for the function of caseins, i.e. the formation of micelles and the binding of Ca2+. In κ-caseins all the prosthetic sugar groups are linked by O-glycosidic linkages: their number varies from 0 to 5 in bovine κ-casein and up to 10 in human κ-casein. The structures of the known κ-casein carbohydate moieties are described. Finally the milk clotting process (interaction κ-casein/chymosin) is compared to the blood clotting process (interaction fibrinogen/thrombin): a large number of similarities could be noted between both clotting phenomena.
The second part of the review is devoted to the study of short casein peptides endowed with various biological activities. Some of them behaved as immunomodulators or casomorphins or angiotensin I converting enzyme inhibitors; others demonstrated an effect on platelet functions. A ‘strategic zone’ containing immunostimulating and opioid peptides could be located in cow and human β-caseins. Furthermore bitter peptides, emulsifying peptides, calcium absorption enhancing peptides, chymosin-inhibiting peptides, have also been described and several further properties have been attributed to the κ-caseinoglycopeptide; two tetrasaccharides isolated from the latter possess blood group activities.
In conclusion caseins, the main milk proteins, should not only be considered as a nutriment but as a possible source of biologically active components.
If, in the future, some of the discussed active peptides cannot be characterized in vivo, they can all, nevertheless, be synthesized and used either as food additives or in pharmacology.
Bioactive peptides have been identified as digestion products of several food proteins. All the bioactive sequences are hidden in an inactive state inside the polypeptide chain of the larger protein. Milk proteins are a rich source of biologically active peptides such as exorphins (casomorphins), phosphopeptides and immunopeptides. Such peptides are released during intestinal digestion of caseins and whey proteins. They may be involved in regulation of nutrient entry and influence the postprandial metabolism via stimulation of the secretion of hormones. Furthermore, they may exert a stimulating effect on the immune system. These findings offer new aspects for evaluating the nutritive value of food proteins. Moreover, bioactive peptides have already found interesting applications as dietary supplements and as pharmaceutical preparations.
Angiotensin-converting enzyme (ACE) has been identified as a prominent brush border membrane-bound enzyme of human jejunum. In this study, we purified brush border membrane vesicles enriched in ACE, and characterized the ACE with regard to (a) its stability in the membrane, (b) substrate hydrolysis kinetics compared with pulmonary endothelial ACE, and (c) pharmacologic interaction with Ramipril. These investigations resulted in the following findings. The uninhibited enzyme is stable in native membranes in vitro, with a half-life of 195 +/- 7 h. Kinetic analysis of ACE hydrolysis activity revealed the presence of a single enzyme species, which yielded a high Vmax and displayed a Km similar to purified ACE from lung endothelium. Brush border ACE was inhibited by Ramipril, one of the most specific and potent orally administered ACE inhibitors indicated for hypertension. We determined the brush border ACE value of IC50 = 3 X 10(-9) M Ramipril-diacid, which is the same value for serum and lung ACE. Brush border ACE remains 100% inhibited by 10 microM Ramipril during at least 8 days in vitro. The data indicate that ACE is a prominent jejunal brush border enzyme that behaves pharmacologically and kinetically like its peripheral circulation counterpart. This study suggests that high doses of orally administered ACE inhibitors may affect intestinal epithelial function.
The in vivo formation of phosphopeptides derived from bovine casein was proved in small intestinal chyme of minipigs after ingestion of a diet containing casein. The main phosphopeptide was identified as a fragment of alpha s1-casein (f 66-74): SerP-SerP-SerP-Glu-Glu-Ile-Val-Pro-Asn. It is discussed, that caseinophosphopeptides are likely to promote the intestinal absorption of calcium and trace elements.