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

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1541-4337.2005.tb00075.x

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

Soy consumption has been associated with many potential health benefits in reducing chronic diseases such as obesity, cardiovascular disease, insulin-resistance/type II diabetes, certain type of cancers, and immune disorders. These physiological functions have been attributed to soy proteins either as intact soy protein or more commonly as functional or bioactive peptides derived from soybean processing. These findings have led to the approval of a health claim in the USA regarding the ability of soy proteins in reducing the risk for coronary heart disease and the acceptance of a health claim in Canada that soy protein can help lower cholesterol levels. Using different approaches, many soy bioactive peptides that have a variety of physiological functions such as hypolipidemic, anti-hypertensive, and anti-cancer properties, and anti-inflammatory, antioxidant, and immunomodulatory effects have been identified. Some soy peptides like lunasin and soymorphins possess more than one of these properties and play a role in the prevention of multiple chronic diseases. Overall, progress has been made in understanding the functional and bioactive components of soy. However, more studies are required to further identify their target organs, and elucidate their biological mechanisms of action in order to be potentially used as functional foods or even therapeutics for the prevention or treatment of chronic diseases.

/pdf/soybean-bioactive-peptides-and-their-functional-properties-g82qjm9ykh.pdf

Soybean Bioactive Peptides and Their Functional Properties

Colorectal cancer is the second leading cause of mortality in the United States. In the United States, the cumulative lifetime risk of developing colorectal cancer for both men and women is 6%. Despite advances in the management of this disease, the 5-year survival rate in the United States in only 62%. Because only 38% of patients are diagnosed when the cancers are localized to the bowel wall, it is likely that widespread implementation of screening could significantly improve the outcome. Colorectal cancer screening is cost effective, irrespective of the methods used. In addition to currently available methods (fecal occult blood, flexible sigmoidoscopy, colonoscopy, and double contrast barium enema), computed tomographic colonography (virtual colonoscopy) and stool-based molecular screening are under development. Four classes of chemopreventive compounds have demonstrated efficacy in reducing recurrent colorectal adenomas and/or cancer in randomized, controlled trials. They are selenium, calcium carbonate, hormone replacement therapy, and nonsteroidal anti-inflammatory drugs. The mechanisms of action of nonsteroidal anti-inflammatory drugs include inhibition of the cyclooxygenase system as well as cyclooxygenase-independent effects. Considerable effort is being expended to define chemopreventive activity, optimal dose, administration schedule, and toxicity for the coxibs in adenoma recurrence prevention trials. The threshold for tolerating toxicities is very low in asymptomatic individuals at minimally increased risk for colorectal neoplasia.

Colorectal Cancer Prevention

Biologically active compounds with different modes of action, such as, antiproliferative, antioxidant, antimicrotubule, have been isolated from marine sources, specifically algae and cyanobacteria. Recently research has been focused on peptides from marine animal sources, since they have been found as secondary metabolites from sponges, ascidians, tunicates, and mollusks. The structural characteristics of these peptides include various unusual amino acid residues which may be responsible for their bioactivity. Moreover, protein hydrolysates formed by the enzymatic digestion of aquatic and marine by-products are an important source of bioactive peptides. Purified peptides from these sources have been shown to have antioxidant activity and cytotoxic effect on several human cancer cell lines such as HeLa, AGS, and DLD-1. These characteristics imply that the use of peptides from marine sources has potential for the prevention and treatment of cancer, and that they might also be useful as molecular models in anticancer drug research. This review focuses on the latest studies and critical research in this field, and evidences the immense potential of marine animals as bioactive peptide sources.

https://www.mdpi.com/1660-3397/10/5/963/pdf

Bioactive peptides and depsipeptides with anticancer potential: sources from marine animals.

In the past few years, increasing interest has been directed to bioactive peptides of animal and plant origin: in particular, researchers have focused their attention on their mechanisms of action and potential role in the prevention and treatment of cancer, cardiovascular and infective diseases. We have developed a search strategy to identify these studies in PubMed (January 1980 to May 2016); particularly those papers presenting comprehensive reviews or meta-analyses, plus in vitro and in vivo studies and clinical trials on those bioactive peptides that affect cardiovascular diseases, immunity or cancer, or have antioxidant, anti-inflammatory and antimicrobial effects. In this review we have mostly focused on evidence-based healthy properties of bioactive peptides from different sources. Bioactive peptides derived from fish, milk, meat and plants have demonstrated significant antihypertensive and lipid-lowering activity in clinical trials. Many bioactive peptides show selective cytotoxic activity against a wide range of cancer cell lines in vitro and in vivo, whereas others have immunomodulatory and antimicrobial effects. Furthermore, some peptides exert anti-inflammatory and antioxidant activity, which could aid in the prevention of chronic diseases. However, clinical evidence is at an early stage, and there is a need for solid pharmacokinetic data and for standardized extraction procedures. Further studies on animals and randomized clinical trials are required to confirm these effects, and enable these peptides to be used as preventive or therapeutic treatments.

Linked Articles
This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bph.13608

Potential role of bioactive peptides in prevention and treatment of chronic diseases: a narrative review.

The Bowman-Birk inhibitor (BBI) is a soybean-derived serine protease inhibitor and a potential cancer chemopreventive agent for humans. In this Phase I clinical trial, BBI concentrate was administered as a single oral dose to 24 subjects with oral leukoplakia. Pharmacokinetics of BBI was analyzed, and subjects were monitored clinically for toxic effects. Subjects received between 25 and 800 chymotrypsin inhibitor units (CIU) of the compound in a dose escalation trial. BBI was taken up rapidly, and a metabolic product of BBI was excreted in the urine within 24-48 h. No clinical or laboratory evidence of toxicity was observed in the study. Protease activity was also measured in buccal cells to evaluate usefulness as a biomarker. Single-dose BBI concentrate administered up to 800 CIU was well tolerated and appeared to be nontoxic. Further investigation in Phase II clinical trials is being done.

/pdf/single-dose-administration-of-bowman-birk-inhibitor-4shnzo3r4g.pdf

Single-Dose Administration of Bowman-Birk Inhibitor Concentrate in Patients with Oral Leukoplakia

The protease catalyzing the hydrolysis of the tripeptide fluorescence substrate, butoxycarbonyl-valine-proline-arginine-(7-amino-4-methylcoumarin) (Boc-Val-Pro-Arg-MCA) and the neu oncogenic protein are potentially useful biomarkers for human cancer prevention studies. In the present study, we standardized a specific substrate hydrolysis method for measuring this protease activity in human oral mucosal cells and characterized the relationship between neu oncogene expression and protease activity in patients enrolled in an oral cancer prevention trial using Bowman Birk Inhibitor Concentrate (BBIC) as the cancer preventive agent. The results demonstrate that changes in the protease activity in oral mucosal cells after BBIC treatment correlated with the changes in the neu protein levels in oral mucosal cells (r = 0.726, P < 0.001) and serum (r = 0.675, P < 0.001), suggesting that the Boc-Val-Pro-Arg-MCA hydrolyzing activity can be as useful as neu oncogene expression as a cancer biomarker. In the 25 patients enrolled in the study, the level of neu protein in oral mucosal cells correlated with the serum neu protein concentration in the patients before BBIC treatment (r = 0.645, P < 0.001). However, such a correlation was not observed after the BBIC treatment, suggesting that BBI may inhibit serine protease(s) involved in the cleavage of neu protein on the cell surface, thereby preventing the release of the extracellular domain of neu protein into the circulation. By inhibiting the cleavage of neu protein on the cell surface, BBI could prevent malignant and premalignant cells expressing high levels of neu protein antigen from escaping host immunological surveillance control.

/pdf/relationship-between-protease-activity-and-neu-oncogene-3sl9x0wrzn.pdf

Wan Xs

Papers

Single-Dose Administration of Bowman-Birk Inhibitor Concentrate in Patients with Oral Leukoplakia

Relationship between protease activity and neu oncogene expression in patients with oral leukoplakia treated with the Bowman Birk Inhibitor.