Functional peptides derived from rice bran proteins

Rice bran has been predominantly used in the feed industry, and only recently it has attracted greater attention in terms of human nutrition with increasing knowledge of its bioactivity. A growing interest is the analysis of physiologically active peptides derived from rice bran proteins. In this paper, the bioactivities of rice bran proteins hydrolysates and peptides are reviewed based on recent studies. These enzymatic hydrolysates and peptides exert various biological activities including antioxidant, antidiabetic, anticancer and inhibitory activity for angiotensin converting enzyme (ACE), which may ultimately prevent certain chronic diseases. Nevertheless, these functionalities can be highly associated with their corresponding structural characteristics, in particular specific sequences and molecular weight distribution. This article may facilitate the expansion of the prospective applications of the bioactive peptides in a number of fields and provide some clues of the relationship between peptides structure and functionality for future research.     

Alpha‐Lactalbumin: Its Production Technologies and Bioactive Peptides

ABSTRACT: Alpha‐lactalbumin (α‐La), a globular protein found in all mammalian milk, has been used as an ingredient in infant formulas. The protein can be isolated from milk using chromatography/gel filtration, membrane separation, enzyme hydrolysis, and precipitation/aggregation technologies. α‐La is appreciated as a source of peptides with antitumor and apoptosis, antiulcerative, immune modulating, antimicrobial, antiviral, antihypertensive, opioid, mineral binding, and antioxidative bioactivities, which may be utilized in the production of functional foods. Nanotubes formed by the protein could find applications in foods and pharmaceuticals, and understanding its amyloid fibrils is important in drawing strategies for controlling amyloidal diseases. Bioactive peptides in α‐La are released during the fermentation or ripening of dairy products by starter and nonstarter microorganisms and during digestion by gastric enzymes. Bioactive peptides are also produced by deliberate hydrolysis of α‐La using animal, microbial, or plant proteases. The occurrence, structure, and production technologies of α‐La and its bioactive peptides are reviewed.     

Fibrillar structures in food

Assembly of proteins or peptides into fibrils is an important subject of study in various research fields. In the field of food research, the protein fibrils are interesting candidates as functional ingredients. It is essential to understand the formation and properties of the fibrils for successful application of the fibrils in food products. This paper describes the impact of recent research on the general view of the process of fibril formation from β-lg and the properties of the fibrils that are formed, leading to better control of applications for the fibrils. There is a need for a better understanding of the behavior of fibrils in more complex food systems.     

Fibrillation of whey protein isolate by radio frequency heating for process efficiency: Assembly behavior,structural characteristics,and in-vitro digestion

In this study, a novel technology involving radio frequency heating (RF) was applied to promote the production of whey protein isolate (WPI) nanofibrils. As the prolonged treatment time, gradual increases were observed in the conversion rate (>16 h with the conventional processes), fluorescence intensity, and free amino acid content of WPI. During the fibrillation process, WPI was hydrolyzed into small molecular weight peptides that self-assembled into fibrils, resulting in a significant increase in the ζ-potential and surface hydrophobicity. Conformational and structural changes that favored an increased content of β-sheets were confirmed by Fourier transform infrared and circular dichroism spectroscopy. A linear fibril structure with a proper aspect ratio (length/diameter, 35.50 ± 0.39) formed at 7 h. Moreover, the good resistance to proteolytic digestion (especially gastric stage) of certain fibrils makes them suitable for application as nutraceutical delivery vehicles. Our findings move a step forward for WPI fibrillation by RF heating.     

Staphylococcus aureus mastitis: pathogenesis and treatment with bovine interleukin-1 beta and interleukin-2.

Polymorphonuclear leukocytes play a central role in the pathogenesis of bovine mastitis. Intramammary challenge with Staphylococcus aureus was shown to induce both quantitative and qualitative changes in mammary gland polymorphonuclear leukocytes. Intramammary infusion of recombinant bovine interleukin-1 beta and interleukin-2 elicited a similar cellular response. Staphylococcus aureus, interleukin-1 beta, and interleukin-2 all increased the number of somatic cells after intramammary infusion and activated the inducible superoxide production in milk polymorphonuclear leukocytes. Interleukin-2 also activated phagocytosis of these cells, and their activation was maintained for 3 to 5 d after intramammary administration. Interleukin-1 beta and interleukin-2 were moderately effective in the therapy of experimental S. aureus mastitis. Approximately 54% of the glands treated with interleukin-1 beta responded to therapy by transiently clearing the milk of S. aureus, 30% of which relapsed, and a total of 38% of the treated glands remained cured. In contrast, 83% of glands treated with interleukin-1 beta responded to therapy, but 50% of these quarters relapsed. A total of 42% of the quarters treated with interleukin-1 beta remained cured. Homologous recombinant cytokines are effective immunomodulators that augment natural defensive mechanisms similar to the normal response to pathogens and may prove to be suitable alternatives to, or may be used in combination with, antibiotics as effective mastitis therapeutic agents.     

A possible influence of nutrient factors in the mechanism development of the neurodegenerative diseases--alzheimerrs disease and sprongiform encelphalopathy with people

The article presents a review of the literature data, as well as the author's experimental observations concerning the role of nutrient components in the development of neurodegenerative diseases of amyloidal nature. In particular, the role of antioxidants in the prevention of the accumulation of oxidized proteins blocking the chaperone system is discussed. A separate section is devoted to the formation of the large amorphous aggregates on the association of caseins with the precursors of amyloidal structures (amyloidal beta peptidel-42 and recombinant prions). A possible role of nutrient factors in the development of the neurodegenerative diseases is discussed.     

Cuminaldehyde as the Major Component of Cuminum cyminum,a Natural Aldehyde with Inhibitory Effect on Alpha‐Synuclein Fibrillation and Cytotoxicity

Fibrillation of alpha‐synuclein (α‐SN) is a critical process in the pathophysiology of several neurodegenerative diseases, especially Parkinson's disease. Application of bioactive inhibitory compounds from herbal extracts is a potential therapeutic approach for this cytotoxic process. Here, we investigated the inhibitory effects of the Iranian Cuminum cyminum essential oil on the fibrillation of α‐SN. Analysis of different fractions from the total extract identified cuminaldehyde as the active compound involved in the antifibrillation activity. In comparison with baicalein, a well‐known inhibitor of α‐SN fibrillation, cuminaldehyde showed the same activity in some aspects and a different activity on other parameters influencing α‐SN fibrillation. The presence of spermidine, an α‐SN fibrillation inducer, dominantly enforced the inhibitory effects of cuminaldehyde even more intensively than baicalein. Furthermore, the results from experiments using preformed fibrils and monobromobimane‐labeled monomeric protein also suggest that cuminaldehyde prevents α‐SN fibrillation even in the presence of seeds, having no disaggregating impact on the preformed fibrils. Structural studies showed that cuminaldehyde stalls protein assembly into β‐structural fibrils, which might be achieved by the interaction with amine groups through its aldehyde group as a Schiff base reaction. This assumption was supported by FITC labeling efficiency assay. In addition, cytotoxicity assays on PC12 cells showed that cuminaldehyde is a nontoxic compound, treatment with cuminaldehyde throughout α‐SN fibrillation showed no toxic effects on the cells. Taken together, these results show for the first time that the small abundant natural compound, cuminaldehyde, can modulate α‐SN fibrillation. Hence, suggesting that such natural active aldehyde could have potential therapeutic applications.     

Glucan structure in a fragile mutant of Saccharomyces cerevisiae

The phenotype of VY1160 fragile Saccharomyces cerevisiae mutant is characterized by cell lysis upon transfer to hypotonic solutions and increased permeability of cells growing in osmotically stabilized media. Two mutations, srb1 and ts1, have been identified in VY1160 cells and previous studies have shown that the increased permeability is due to the ts1 mutation which causes a shortening of mannan side-chains. Here we report that the srb1 mutation, which is the genetic determinant of cell lysis, is responsible for quantitative and structural changes of glucans. Experiments with isogenic single mutation strains, genetic studies coupled with quantitative measurements of glucan content per cell, and methylation analysis of glucans provide evidence that srb1 mutation leads to i) formation of mechanically unstable cell wall network made of insoluble glucan fibrils which are shorter and contain beta(1-6) inter-residue linkages and ii) insufficient filling of the space between the fibrils due to a shortage of the alkali-soluble glucan. Although growing exponentially in osmotically stabilized media, the srb1 cells cannot resist an osmotic shock and, hence, burst immediately.     

小麦麸质蛋白相关性疾病的研究进展

小麦是主要的粮食作物,但也可引发多种过敏性疾病和自身免疫性疾病。麸质蛋白的摄入,是引起这些疾病的关键因素,麸质蛋白主要存在于小麦中,但也存在于大麦,黑麦和燕麦中。特别是小麦麸质蛋白因含有大量的非极性氨基酸和谷氨酰胺而耐胃肠道酶消化,生成使部分人群致病的毒性肽。麸质蛋白相关性疾病的全球患病率接近5%,已经严重影响了部分人群的生活质量,甚至危及生命,已成为全球性不可回避的食品安全问题之一。本文主要对麸质蛋白结构、麸质蛋白相关性疾病的发病机制、流行病学、诊断和治疗进行了概述,为小麦的安全食用提供参考。     

Effect of heat-induced formation of rice bran protein fibrils on morphological structure and physicochemical properties in solutions and gels

The effects of heat-induced rice bran protein (RBP) fibrils on structure and properties of solutions and gels in a complex system were investigated using transmission electron microscopy (TEM), atomic force microscopy (AFM), Congo red spectral analysis, and circular dichroism (CD). Planar and 3-dimensional images of RBP fibrils all revealed structural details. A Congo red spectral shift indicated fibril formation. Fibril secondary structural components exhibited differences at pH 2.0 and pH 7.0. The β-type was decreased with an increased pH. Rheological results exhibited shear thinning behavior for all solutions. Addition of fibrils to RBP solutions, which made the system complex, resulted in an order of magnitude increase in viscosity and shear stress. Adding fibrils to RBP solutions accelerated the kinetics of gel formation, resulting in an increase in gel strength. Scanning electron microscopy (SEM) images showed gel network structural differences with and without fibrils at different pH values.     

Technological functionality and biological properties of food protein nanofibrils formed by heating at acidic condition

BackgroundNanofibrillation of proteins by heating at extremely acidic condition for long durations (several hours to days) is studied enthusiastically in food science. The process progresses by the unidirectional self-assembly of peptides as building units of the fibrils.Scope and approachThis communication provides a review on the underlying mechanism of protein fibrillation, and various technological properties of the fibrils, followed by discussing their biological and cellular effects.Key findings and conclusionsFibrillation of proteins and addition of the fibrils into liquid foods causes a significant increase of apparent viscosity. Nevertheless, certain post-fibrillation processes such as freeze-drying may result in viscosity reduction. Fibrils form cohesive viscoelastic interfaces, bringing about high foam and emulsion stability. The presence of non-fibrillated peptides and low molecular weight surfactants influence the foaming and emulsification properties of fibrillated protein solutions. Fibrillated protein can yield cold-set gels at extremely low concentrations, which is attributed to formation of space filling networks. Reinforcing polymeric films, conferring hydrophilic character to graphene, developing drug and nutraceutical delivery vehicles such as microcapsules, microgels and fibrillosome and utilization (mostly as scaffolds) in fabrication of biosensors and bio-sorbents are the other applications of protein fibrils. Fibrillation may increase the antioxidant activity of proteins. It can also influence protein digestibility. Fibrils do not exert any major toxicity towards human cell lines and can be exploited as biomimetic cell culture platforms and cellular transport shuttles.     

Characterization of a Main Extracellular Matrix Autoenzyme from the Dermis of Sea Cucumber Stichopus monotuberculatus: Collagenase

Sea cucumber is easy to undergo autolysis, causing serious economic loss in the aquaculture, fishery, and food processing. However, research on the autolysis of sea cucumber is limited. In the present study, the autoenzyme that could hydrolyze the structural protein of body wall was identified and characterized in sea cucumber Stichopus monotuberculatus. Although the main edible part of sea cucumber was the body wall, its microstructure was shown to be almost composed of collagen fibers belonging to extracellular matrix, indicating that the body wall of S. monotuberculatus belonged to dermis tissue. Starting from this perspective, crude collagen fibrils from dermis of S. monotuberculatus was isolated, and pepsin solubilized collagen was also obtained by hydrolyzing collagen telopeptides from crude collagen fibrils. Crude collagen fibrils and pepsin solubilized collagen were then acting as substrates, respectively, to identify dermis autoenzyme which had hydrolytic activity on dermis collagen. After that, a collagenase of 45 kDa was identified with the method of collagen zymograph, and the content of soluble protein was suppressed by collagenase inhibitor significantly in the autolysis of dermis. Finally, the effect of environmental conditions on collagenase activity was studied, results showed its best activity was at 40°C and pH 8, and divalent metal ion Mn²⁺ was essential for its activity. As a whole, our results showed that the dermis of sea cucumber was composed of collagen fibers, and collagenase was the main enzyme resulting in autolysis of sea cucumber.     

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

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

The Inhibition of Advanced Glycation End Products by Carnosine and Other Natural Dipeptides to Reduce Diabetic and Age‐Related Complications

As people age they are at a greater risk for many disorders including cardiovascular, renal, and neurodegenerative diseases, and these conditions are exacerbated by diabetes. An important cause of the maladies associated with both age and diabetes is the formation of advanced glycation end products (AGEs). AGE formation is initiated by glycation reactions between reducing sugars and free amine groups. A cascade of other reactions follows, leading to alterations in membrane function and damage to the proteome, such as protein crosslinking. Compounds that prevent these reactions are currently being researched, but peptides hold great potential as they tend to lack toxicity, are absorbed intact, are easily produced, and are cheaper than other options. Of the peptides researched, carnosine is the most promising. Research suggests that carnosine is absorbed into the plasma unaltered and intact. Carnosine has been shown to prevent AGE formations through reduction of blood glucose, prevention of early glycation, and even reversing previously formed AGEs. Other promising peptides and amino acids include β‐alanine, L‐histidine, homocarnosine, anserine, and glutathione. If bioactive peptides and amino acids can minimize the formation of AGEs, foods containing these peptides could be used to improve health.     

氧化应激参与丙烯酰胺致神经细胞凋亡及炎症反应的研究进展

丙烯酰胺（acrylamide,AA）是一种重要的工业原料,具有神经毒性、生殖毒性、遗传毒性及潜在致癌性。2002年,AA首次被报道作为美拉德反应的副产物之一,在油炸和焙烤等热加工高淀粉食品中广泛存在。氧化应激（oxidative stress, OS）是机体内氧化与抗氧化系统之间的平衡被破坏而造成的应激状态,可被多种环境因素激活,并与细胞凋亡及炎症反应的发生密切相关。大量研究发现,OS常伴随着AA诱导的中枢神经系统细胞凋亡及炎症反应发生,也是AA与神经退行性疾病相关性的重要连接纽带。本文就OS在AA诱导的凋亡及炎症反应中的作用进行综述,为AA神经毒性机制的深入研究及其毒性干预提供参考。     

Rational Design of Amyloid‐Like Fibrillary Structures for Tailoring Food Protein Techno‐Functionality and Their Potential Health Implications

To control and enhance protein functionality is a major challenge for food scientists. In this context, research on food protein fibril formation, especially amyloid fibril formation, holds much promise. We here first provide a concise overview of conditions, which affect amyloid formation in food proteins. Particular attention is directed towards amyloid core regions because these sequences promote ordered aggregation. Better understanding of this process will be key to tailor the fibril formation process. Especially seeding, that is, adding preformed protein fibrils to protein solutions to accelerate fibril formation holds promise to tailor aggregation and fibril techno‐functionality. Some studies have already indicated that food protein fibrillation indeed improves their techno‐functionality. However, much more research is necessary to establish whether protein fibrils are useful in complex food systems and whether and to what extent they resist food processing unit operations. In this review the effect of amyloid formation on gelation, interfacial properties, foaming, and emulsification is discussed. Despite their prevalent role as functional structures, amyloids also receive a lot of attention due to their association with protein deposition diseases, prompting us to thoroughly investigate the potential health impact of amyloid‐like aggregates in food. A literature review on the effect of the different stages of the human digestive process on amyloid toxicity leads us to conclude that food‐derived amyloid fibrils (even those with potential pathogenic properties) very likely have minimal impact on human health. Nevertheless, prior to wide‐spread application of the technology, it is highly advisable to further verify the lack of toxicity of food‐derived amyloid fibrils.     

Impact of Milk Derived β-Casomorphins on Physiological Functions and Trends in Research: A Review

β-Casomorphins are a group of opioid peptides released during gastrointestinal digestion or food processing from the β-casein of milk protein. Consequently, milk can be divided into A1 and A2 “like” groups depending upon the presence or absence of proline or histidine at the 67th position of β-casein. A1 “like” milk is postulated to be a source of BCM-7 as histidine allows the cleavage at this position, while A2 “like” milk has proline that resists the hydrolysis. On one hand, BCM-7 has been implicated as a risk factor for cardiovascular diseases, type I diabetes, and neurological disorders. On the other hand, various physiological effects of these peptides have also been documented, i.e., secretion of mucus, increased activity of superoxide dismutase and catalase, increased levels of prolactin, and analgesic role. In addition, many evidences correlate these peptides with various immunological functions, such as development of innate immunity, lymphocyte proliferation and cellular immunity, role in autoimmune diseases, histamine release, and allergy. In conclusion, the role of β-casomorphins in physiological functions remains controversial and more research with improved diagnostic techniques is needed to unravel the mechanism and study physiological functions of β-casomorphins. Thus, health-related aspects of β-casomorphins (positive, negative, and immunological impacts) have been comprehensively reviewed in this article.     

Formation and Degradation of Beta-casomorphins in Dairy Processing

Milk proteins including casein are sources of peptides with bioactivity. One of these peptides is beta-casomorphin (BCM) which belongs to a group of opioid peptides formed from β-casein variants. Beta-casomorphin 7 (BCM7) has been demonstrated to be enzymatically released from the A1 or B β-casein variant. Epidemiological evidence suggests the peptide BCM 7 is a risk factor for development of human diseases, including increased risk of type 1 diabetes and cardiovascular diseases but this has not been thoroughly substantiated by research studies. High performance liquid chromatography coupled to UV-Vis and mass spectrometry detection as well as enzyme–linked immunosorbent assay (ELISA) has been used to analyze BCMs in dairy products. BCMs have been detected in raw cow's milk and human milk and a variety of commercial cheeses, but their presence has yet to be confirmed in commercial yoghurts. The finding that BCMs are present in cheese suggests they could also form in yoghurt, but be degraded during yoghurt processing. Whether BCMs do form in yoghurt and the amount of BCM forming or degrading at different processing steps needs further investigation and possibly will depend on the heat treatment and fermentation process used, but it remains an intriguing unknown.     

生物活性肽的制备、分离纯化、鉴定以及构效关系研究进展

生物活性肽来源广泛,易消化利用,安全性高,且因具有降胆固醇、降血压、抗菌、抗氧化等众多生物活性而成为食品领域研究的热点。然而生物活性肽在食品中的应用受其结构和功能的影响显著,其结构与功能又与生物活性肽的制备、分离纯化、结构鉴定密不可分。本文分别介绍了生物活性肽的制备方法、分离纯化方法、结构鉴定方法,并阐述了各种方法的原理、优缺点以及适用对象,分析了生物活性肽的构效关系和未来发展方向,以期为筛选安全有效的多肽提供新的研究思路,并为多肽的应用提供理论依据。