Bioactive Proteins And Peptides As Functional Foods And Nutraceuticals Pdf
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- Food-Derived Bioactive Peptides on Inflammation and Oxidative Stress
Chronic diseases such as atherosclerosis and cancer are now the leading causes of morbidity and mortality worldwide. Inflammatory processes and oxidative stress underlie the pathogenesis of these pathological conditions.
Bioactive peptides derived from food proteins have been evaluated for various beneficial effects, including anti-inflammatory and antioxidant properties. In this review, we summarize the roles of various food-derived bioactive peptides in inflammation and oxidative stress and discuss the potential benefits and limitations of using these compounds against the burden of chronic diseases. Chronic noncommunicable diseases such as cardiovascular diseases and cancer make up an increasing share of the global disease burden.
Indeed, cardiovascular diseases such as atherosclerosis and its complications are now the leading cause of mortality and morbidity worldwide, closely followed by various cancers [ 3 , 4 ]. Increased life spans have also meant corresponding increase in aging-related diseases in both developing and developed nations which may overwhelm their health care systems.
Although atherosclerosis, cancers, and aging-related diseases can have diverse etiologies, they share many underlying pathological mechanisms including abnormalities in inflammatory responses and oxidative stress [ 5 — 7 ]. Thus targeting of the common pathological pathways has gained increasing attention in recent years for both prevention and treatment of chronic diseases.
While a number of commercially available anti-inflammatory and antioxidant drugs exist, none of these are free from side effects. Given the concerns about the side effects from prolonged usage of synthetic compounds, there is growing interest in the therapeutic applications of natural compounds and their derivatives as safer alternatives, either as functional foods or nutraceuticals.
Food proteins from both plant and animal sources have been used to obtain a wide range of bioactive peptides [ 8 ]. Bioactive peptides are generally short peptides 3—20 amino acids derived from proteins that can exert biological activities over and above their expected nutritional value [ 9 ]. Many of these food-derived peptides demonstrate antihypertensive, anti-inflammatory, antidiabetic, and antioxidant properties under experimental conditions [ 10 — 12 ].
While some studies have observed the effects of single peptides, many others have examined protein hydrolysates composed of a mixture of diverse bioactive peptides [ 13 — 15 ]. Given their food-based sources and a perceived lack of serious side effects, bioactive peptides and peptide-rich protein hydrolysates can potentially provide a better alternative to synthetic pharmaceuticals for the prevention and treatment of chronic illnesses that affect an increasing number of people.
While bioactive peptides and peptide-rich protein hydrolysates can have a range of beneficial effects on diverse pathological conditions, this review would mainly focus on their anti-inflammatory and antioxidant actions. We would also discuss the potential challenges that may limit the use of these compounds as novel therapies against the global burden of chronic diseases.
While inflammation is essential for resistance to microbial infections and wound healing, excessive and uncontrolled inflammatory changes often lead to chronic diseases. Indeed, vascular inflammation is an early event in the development of atherosclerosis and its complications such as myocardial infarction and stroke.
Increasing evidence also links chronic inflammation to many types of cancer which further highlights its key role as a mediator of non-communicable illnesses. Despite the significance of inflammation, relatively few therapies have been devised to target the inflammatory component of cardiovascular and malignant diseases.
The nonsteroidal anti-inflammatory drugs NSAIDs like aspirin are widely used to prevent and manage cardiovascular diseases, due to its antithrombotic as well as anti-inflammatory properties [ 16 , 17 ]. Recent studies suggest that NSAIDs may also contribute to beneficial effects against cancers of the gastrointestinal system, further broadening the potential for anti-inflammatory therapies [ 18 ].
However, the presence of well-known side effects such as gastric bleeding and ulceration preclude the long-term use of NSAIDs for a large part of the population. Inflammation is a complex and multisystem event affecting a wide range of cells, tissues, and organs.
The vascular endothelium plays a key role as a gate keeper for the extravasation of leukocytes which is a hallmark of inflammation. However, tissue macrophages, epithelial cells, and fibroblasts are often involved in the generation of mediators which impinge upon and subsequently activate the endothelium through expression of leukocyte adhesion molecules like intercellular adhesion molecule-1 ICAM-1 and vascular cell adhesion molecule-1 VCAM-1 which recruit leukocytes from the bloodstream and lead to their extravasation through a sequential cascade that involves tethering, rolling, activation, firm adhesion, and, finally, transmigration across the endothelial barrier.
Thus, the markers of inflammation include activation of proinflammatory signaling cascades, upregulation of leukocyte adhesion molecules, tissue infiltration of leukocytes, and increased levels of cytokines and chemokines in the circulation. Given the complexity and diversity of the inflammatory response, an investigation of potential anti-inflammatory agents involves the study of their effects on several of these markers, often using different cellular and intact animal systems for validation.
Much of the recent knowledge on bioactive peptides has been based on studies performed in cultured mammalian cells. Cell culture systems offer fast, economically feasible, and reproducible assays to analyze and validate the effects of many different compounds on a wide range of inflammatory markers. Peptides and protein hydrolysates derived from food sources such as milk, egg, fish, meat, and soybeans to name a few have all been tested for potential beneficial effects in these systems.
Bioactive peptides from milk have been among the first food-derived peptides studied. The tripeptides VPP and IPP, derived from bacterial fermentation of casein, demonstrate inhibitory effects on angiotensin converting enzyme ACE in addition to stimulation of nitric oxide NO and bradykinin-mediated vasorelaxant pathways, thus suppressing the prohypertensive and proinflammatory mechanisms associated with hypertension and atherosclerosis [ 21 ].
Recently, a more direct anti-inflammatory role for VPP has been shown by its ability to attenuate leukocyte-endothelial interactions in vitro , largely through inhibition of proinflammatory c-Jun N-terminal kinase JNK, a type of MAP kinase pathway [ 22 ].
Casein hydrolysates generated by enzymatic digestion and containing a mixture of peptides have also been evaluated for anti-inflammatory properties.
For example, digestion of casein with Corolase yields preparations that demonstrate anti-inflammatory effects on activated macrophages [ 23 ]. Hydrolysates of whey proteins also show promise in inhibition of inflammatory responses in respiratory and intestinal epithelial cells [ 24 , 25 ]. Lactoferrin is a milk protein with antimicrobial properties which also exerts anti-inflammatory effects on activated macrophages [ 26 ]. Hydrolysis of lactoferrin yields the bioactive peptide lactoferricin, which demonstrates anti-inflammatory effects on human cartilage and synovial cells, suggesting potential benefits in arthritis management [ 27 , 28 ].
Egg is another nutritious dietary component that is a source for many bioactive peptides [ 31 ]. These anti-inflammatory properties are also observed in conjunction with antioxidant and ACE inhibitory effects, further enhancing the beneficial actions [ 34 ].
Interestingly, these beneficial effects require the presence of an intact tripeptide as the corresponding dipeptides and constituent amino acids alone failed to replicate the anti-inflammatory functions, indicating a structure-function relationship between the tripeptide structure and blockade of inflammation [ 32 ]. Fish and meat are important sources of dietary protein.
Recent findings suggest they also contribute to human health through generation of bioactive peptides; however, detailed studies at the cellular and molecular level are still quite sparse. A fish hydrolysate preparation has been shown to induce proliferation and migration in intestinal epithelial cells, which may contribute to anti-inflammatory and healing properties [ 13 ].
Plant-derived foods are another important source for bioactive compounds including many peptides and protein hydrolysates.
Soybean hydrolysates have yielded several bioactive peptides with anti-inflammatory effects on macrophage cell lines, with preparations from germinated beans eliciting the stronger responses [ 35 ]. The presence of an RGD motif in lunasin and similar peptides is believed to contribute to their anti-inflammatory effects, potentially involving antagonism of integrin signaling and downstream proinflammatory cascades [ 39 ].
Based on the encouraging findings from cell-based studies, several bioactive peptides and hydrolysates have now been tested in animal models of human diseases. A number of different inflammatory models, typically experimentally induced colitis, arthritis, atherosclerosis, and respiratory tract inflammation, have been used.
As much of this work has been performed only within the last few years, large-scale human trials are still lacking, although a few smaller studies on humans have shown some therapeutic promise. Not surprisingly, milk-derived peptides have been in the forefront of in vivo studies of anti-inflammatory properties.
The tripeptides VPP and IPP appear to be beneficial in a model of intestinal enterocolitis by their mediation of anti-inflammatory effects [ 40 ]. In addition, these peptides offer protection against the development of atherosclerotic changes in the apolipoprotein E ApoE knockout mice through a concerted action that involves modulation of both inflammatory and hypertensive pathways [ 41 ].
Other peptides and protein hydrolysates from animal sources have been used in several animal models of disease.
In our lab, the egg-derived tripeptide IRW has shown promise in controlling both the hyperactive renin-angiotensin system RAS pathway as well as the exaggerated proinflammatory phenotype in spontaneously hypertensive rats SHRs , a widely used model of hypertension and cardiovascular disease [ 45 ]. Fish protein hydrolysates have demonstrated protective effects on different murine models of colitis, including those induced by dextran sulphate as well as by chronic NSAID usage, suggesting their potential applications in human disease [ 46 — 48 ].
A similar preparation also reduced markers of inflammation and improved the plasma lipid profile in high fat-fed mice, with potential implications for obesity-induced inflammation and vascular disease [ 49 ]. Chicken collagen hydrolysate CCH containing an array of bioactive peptides has been used in rodent models of cardiovascular diseases. In the ApoE deficient mice, CCH administration successfully reduced the plasma levels of inflammatory cytokines in addition to improving the plasma lipid profile [ 50 ].
CCH given to SHRs reduced blood pressure and circulating inflammatory markers while increasing the bioavailability of the beneficial vasorelaxant NO [ 51 ]. A pilot study on human volunteers has also confirmed the antihypertensive effects of CCH although the potential anti-inflammatory mechanisms, if any, remain to be determined [ 52 ]. A number of plant-derived bioactive peptides and peptide-rich hydrolysates have also been tested by in vivo studies.
Feeding of soy protein isolate to rodents which presumably generates bioactive short peptides through intestinal digestion has shown beneficial effects on experimentally induced arthritis [ 53 ] and genetically predisposed atherosclerosis [ 54 ], through the induction of protective anti-inflammatory effects.
Oral intake of a corn gluten hydrolysate also reduced inflammatory injury in a rat model of experimental colitis [ 57 ]. Similarly, ingestion of pyro-glutamyl leucine a bioactive peptide from wheat gluten hydrolysate was shown to protect against dextran sulphate-induced colitis in mice [ 58 ] and chemically induced hepatitis in rats [ 14 ], further supporting the in vivo anti-inflammatory functions of plant-derived peptides.
These anti-inflammatory effects of bioactive peptides and hydrolysates have been summarized in Table 1. A schematic diagram of the potential anti-inflammatory mechanisms of bioactive peptides is also shown Figure 1 demonstrating the effects of these compounds on proinflammatory signaling kinases, pro- and anti-inflammatory cytokines, integrin-dependent signaling, ROS generation, and the renin-angiotensin system.
However, an excess of ROS, both due to excessive production or impaired antioxidant capacities or both, is harmful and leads to what is known as oxidative stress. One example of DNA lesions is the conversion of guanine to 8-hydroxyguanine which affects the methylation of cytosine. Normal methylation of cytosine is considered as a critical step in regulation of gene expression and once it is altered, it may contribute to carcinogenesis [ 64 ].
The final products of this reaction are malondialdehydes MDA which possess carcinogenic properties [ 65 ]. Proteins are another group of macromolecules affected by the ROS. Cleavage of the peptide bond, amino acid modification, and formation of cross-linked peptide aggregates happen during protein oxidation by ROS that leads to formation of protein derivatives possessing highly reactive carbonyl groups ketones and aldehydes which are involved in the complications of diabetes and many age-related diseases [ 66 ].
In addition to destructive effects on macromolecules, ROS also impair vasodilatory responses by reaction with NO. Given this background, there is increasing interest in food proteins and their constituent peptides as potential candidates for use as antioxidants.
Several chemical methods with different mechanisms of action have been developed to measure antioxidant potential of food proteins and peptides. This is because of complexity of oxidative reactions taking place in biological systems. While the DPPH-based assay was among the first ones to be used extensively [ 73 — 76 ], many such assays have been widely used for screening antioxidant peptides. A wide range of antioxidant peptides have been identified from marine organisms including oyster, shrimp, squid, blue mussel, and a variety of fish species tuna, sardine, hoki, sole, and pacific hake after hydrolysis with different enzymes.
Puffer fish hydrolysate produced strong antioxidant action as shown by the ORAC assay compared to many other fish sources [ 77 ]. Both the salmon protein hydrolysate and peptide fractions inhibited the oxidation of linoleic acid [ 78 ]. Blue mussel Mytilus edulis is another source for the production of antioxidant peptides. Milk proteins also contribute much in the context of antioxidant peptides. YFYPEL, a hexapeptide isolated from pepsin hydrolysate of bovine casein, showed antioxidant activity by scavenging superoxide, DPPH, and hydroxyl radicals in vitro [ 81 ].
This casein hydrolysate further inhibited lipid peroxidation and several peptides contributing to antioxidant activity were identified [ 83 ]. Goat milk casein also exhibited enhanced free radical scavenging and metal ion chelating activity following hydrolysis by a combination of neutral and alkaline proteases. Further purification revealed five novel peptides in this hydrolysate with potential antioxidant properties [ 84 ].
Plants are known for antioxidant effects mostly because of their polyphenolic compounds. However recent research indicates the significance of many plant proteins and peptides as novel antioxidant agents. The potential of commercially available microbial proteases to enhance antioxidant potential of soy and corn proteins has been recently demonstrated [ 85 , 86 ].
In a recent study the antioxidant activity of chickpea albumin hydrolysate through in vitro radical scavenging and reducing power assays has been assayed. All of the aforementioned peptides were evaluated for antioxidant activity through in vitro methods.
Although these methods are good for screening and assessing preliminary data, there are drawbacks associated with these chemical-based assays including potential lack of relevance to biological systems and altered mechanisms of free radical generation [ 72 , 88 ].
Therefore, it is preferable to use at least two different chemical assays prior to validation of antioxidant activity in more physiologically relevant systems like cells and whole organisms. Cell-based assays as intermediate methods have been used increasingly recently to evaluate the protective effects of antioxidants against oxidative stressors and to elucidate mechanism of action of peptides within cells [ 89 ].
Moreover, cell culture assays are useful for the determination of peptide dosage to exert beneficial antioxidant effects without cytotoxicity for in vivo experiments.
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Milk Protein. A functional food essentially provides a health benefit beyond the basic nutrition, whereas nutraceutical is used to describe an isolated or concentrated molecular extract of bioactive compounds. Milk is a unique food providing a variety of essential nutrients necessary to properly fuel the body. Inactive food proteins can release encrypted bioactive peptides in vivo or in vitro by digestive enzymatic hydrolysis. Bioseparation protocols offer unique possibilities for a number of application areas, e. Many ingredients are included in the wide range of nutraceuticals, such as essential amino acids, conjugated fatty acids, vitamins, minerals and polyphenols. They have already been patented and incorporated in functional foods and nutritional beverages.
This book presents the opportunities for processing eggs to produce value-added food, nutritional, biomedical, functional food, and nutraceutical applications. It provides new evidence around egg consumption with respect to cardiovascular diseases, metabolic syndrome, weight management, mental development, eye, muscle, and ageing health. It also highlights the new discovery regarding egg bioactives that are relevant to anti-oxidants, anti-inflammation, cardiovascular and bone health, anti-microbial and anti-viral activities. Appealing to food scientists, food chemists, researchers in human nutrition specialising in eggs and dairy nutrition, and those involved in egg production, this book is reflecting the trends and innovations in this area of research. Jump to main content. Jump to site search.
Bioactive Proteins and Peptides as Functional Foods and Nutraceuticals highlights recent developments of nutraceutical proteins and peptides.
Food-Derived Bioactive Peptides on Inflammation and Oxidative Stress
Bioactive vegetable proteins and peptides in lipid-lowering; nutraceutical potential. As the last century saw a decline in the burden of nutritional deficiency and infectious disease, the global burden of chronic disease, cardiovascular disease CVD in particular, is increasing. CVD is the leading cause of death in the developed countries. Significant research efforts on the prevention and treatment of this disease have identified elevated plasma cholesterol as a primary risk factor for CVD.
The increased consumer awareness of the health promoting effects of functional foods and nutraceuticals is the driving force of the functional food and nutraceutical market. Bioactive peptides are known for their high tissue affinity, specificity and efficiency in promoting health. For this reason, the search for food-derived bioactive peptides has increased exponentially. Over the years, many potential bioactive peptides from food have been documented; yet, obstacles such as the need to establish optimal conditions for industrial scale production and the absence of well-designed clinical trials to provide robust evidence for proving health claims continue to exist. Other important factors such as the possibility of allergenicity, cytotoxicity and the stability of the peptides during gastrointestinal digestion would need to be addressed.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated. It is tolerant to drought and can grow under poor soil conditions in which other lucrative crops such as groundnut cannot grow. Bambara is a good source of protein comparable to that of cowpea and slightly lower than soya bean.
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Иногда она видела в нем что-то от Дэвида. У них было много общего: настойчивость, увлеченность своим делом, ум. Иногда ей казалось, что Стратмор без нее пропадет; ее любовь к криптографии помогала коммандеру отвлечься от завихрений политики, напоминая о молодости, отданной взламыванию шифров. Но и она тоже многим была обязана Стратмору: он стал ее защитником в мире рвущихся к власти мужчин, помогал ей делать карьеру, оберегал ее и, как сам часто шутил, делал ее сны явью. Хотя и ненамеренно, именно Стратмор привел Дэвида Беккера в АНБ в тот памятный день, позвонив ему по телефону.