Release of antioxidant peptides from the body wall proteins of the sea cucumber Isostichopus fuscus

Proteases from the tentacles of the sea cucumber Isostichopus fuscus were partially purified and used to produce antioxidant peptides from body wall proteins of this marine species. Three proteins (105, 68, and 39 kDa) were identified by SDS-PAGE in the proteolytic extract of the tentacles. Protein hydrolyzates were generated with gelatin and crude protein substrates from body wall, and peptidic fractions lower and higher than 3 kDa were obtained to evaluate their oxygen radical scavenging capacity (ORAC). The 3 kDa-fraction obtained from the crude protein hydrolyzate showed the highest ORAC value (0.92 ± 0.04 μmol Trolox equivalent/mg protein). This fraction was selected to purify peptides potentially responsible for the activity that might be used as ingredients for development of functional foods.A.C.H.-S thanks the National Council of Science and Technology (CONACYT, Mexico) for a graduate scholarship and the “Universidad Autónoma Metropolitana” for giving the marine organisms. B.H.-L. thanks the Ministry of Economy and Competitiveness (MINECO) and the Spanish National Research Council (CSIC) for her “Ramón y Cajal” postdoctoral contract.Peer Reviewe

Lunasin: A Novel Cancer Preventive Seed Peptide

Cancer is one of the leading causes of deaths in the Western world. Approximately one-third of these deaths are preventable by lifestyle factors, including modification of nutritional habits. Studies have demonstrated that adequate nutrition with certain types of foods containing bioactive compounds might offer significant protection against carcinogenesis. Soybeans contain a variety of phytochemicals with demonstrated anticancer activity, including isoflavones, protease inhibitors, and more recently lunasin, a novel cancer preventive seed peptide. Initially isolated from soybean, lunasin has also been reported in barley and wheat. The purpose of this review is to summarize the most recent evidence on the possible benefits of lunasin for cancer prevention

1997-2012: Fifteen Years of Research on Peptide Lunasin

Publisher under CC BY 3.0 license.Peer Reviewe

Péptidos antihipertensivos derivados de proteínas lácteas

La leche es una excelente fuente de nutrientes. Mas allá de su bien documentada función nutricional, la leche ejerce un amplio rango de actividades biológicas que influyen sobre el sistema digestivo y metabólico, el crecimiento y desarrollo de los órganos y la resistencia a diversos trastornos y enfermedades. Estas actividades han sido atribuidas principalmente a las proteínas y péptidos secretados en la leche por la glándula mamaria. Sin embargo, algunas de las actividades biológicas de las proteínas lácteas se encuentran en un estado latente y requieren de procesos de proteolisis para su liberación.Este trabajo ha sido realizado en el marco del Proyecto CYTED XI.24. También se agradece a los Proyectos Consolider 2010 CS-063 y CM-S0505 -AGR-0153 y AGL- 2007 065035. Blanca Hernández-Ledesma disfruta de un contrato post-doctoral Marie-Curie de la Comisión Europea coordinado por el Consejo Superior de Investigaciones Científicas. María del Mar Contreras disfruta de una beca DANONE.Peer Reviewe

Complementary Roles in Cancer Prevention: Protease Inhibitor Makes the Cancer Preventive Peptide Lunasin Bioavailable

9 páginas, 6 figuras.-- et al.[Background]: The lower incidence of breast cancer among Asian women compared with Western countries has been partly attributed to soy in the Asian diet, leading to efforts to identify the bioactive components that are responsible. Soy Bowman Birk Inhibitor Concentrate (BBIC) is a known cancer preventive agent now in human clinical trials. [Methodology/Principal Findings]: The objectives of this work are to establish the presence and delineate the in vitro activity of lunasin and BBI found in BBIC, and study their bioavailability after oral administration to mice and rats. We report that lunasin and BBI are the two main bioactive ingredients of BBIC based on inhibition of foci formation, lunasin being more efficacious than BBI on an equimolar basis. BBI and soy Kunitz Trypsin Inhibitor protect lunasin from in vitro digestion with pancreatin. Oral administration of 3H-labeled lunasin with lunasin-enriched soy results in 30% of the peptide reaching target tissues in an intact and bioactive form. In a xenograft model of nude mice transplanted with human breast cancer MDA-MB- 231 cells, intraperitoneal injections of lunasin, at 20 mg/kg and 4 mg/kg body weight, decrease tumor incidence by 49% and 33%, respectively, compared with the vehicle-treated group. In contrast, injection with BBI at 20 mg/kg body weight shows no effect on tumor incidence. Tumor generation is significantly reduced with the two doses of lunasin, while BBI is ineffective. Lunasin inhibits cell proliferation and induces cell death in the breast tumor sections. [Conclusions/Significance]: We conclude that lunasin is actually the bioactive cancer preventive agent in BBIC, and BBI simply protects lunasin from digestion when soybean and other seed foods are eaten by humans.Project number 05B087 awarded by the American Institute for Cancer Research (http://www.aicr.org/site/PageServer). Project number W81XWH-04-1- 0128 awarded by the United States Department of Defense Congressionally Directed Medical Research Program (https://cdmrp.org). Project LUNAMICE 039241 awarded by the European Commission and the Spanish National Research Council for the Marie-Curie postdoctoral fellowship of BHL.Peer reviewe

Quantitative determination of active Bowman-Birk isoinhibitors, IBB1 and IBBD2, in commercial soymilks

Naturally-occurring serine protease inhibitors of the Bowman-Birk family exert their potential chemopreventive and/or therapeutic properties via protease inhibition. In this study, we have quantified the amounts of active BBI isoinhibitors, IBB1 and IBBD2, in six commercial soymilks. By using cation exchange chromatography, the BBI isoinhibitors were isolated and their specific trypsin inhibitory activity was used to estimate their amounts in soymilk samples. IBB1 and IBBD2 concentrations ranged from 0.44 to 5.20 and 0.27 to 4.60 mg/100 ml of soymilk, respectively; total BBI, considered as the sum of both isoinhibitors, ranged from 0.60 to 9.07 mg/100 ml of soymilk. These data show that physiologically relevant amounts of active BBI are present in commercial soymilk and may exert potential health-promoting effects.A.C. acknowledges support by ERDF-co-financed Grant from the Spanish CICYT (AGL2011-26353). A.C. is involved in COST Action FA1005 INFOGEST on Food Digestion. L.C.B.R. acknowledges support from CAPES (Programa Institucional de Doutorado Sanduíche no Exterior–PDSE process number 9004-11-4), Brazil. We are grateful to the proteomics Facility of University of Cordoba (Spain) for carrying out peptide mass fingerprinting. B.H.-L. thanks Ministry of Economy and Competitiveness for her “Ramón y Cajal” contract.Peer Reviewe

Influence of protein-phenolic complex on the antioxidant capacity of flaxseed (Linum usitatissimum L.) products

The impact of the naturally present phenolic compounds and/or proteins on the antioxidant capacity of flaxseed products (phenolic fraction, protein concentrates, and hydrolysates) before and after simulated gastrointestinal digestion was studied. For that, whole and phenolic reduced products were assessed. Four glycosylated phenolic compounds (secoisolariciresinol and ferulic, p-coumaric, and caffeic acids) were identified in flaxseed products. Phenolic fraction exerts the highest antioxidant capacity that increased by alkaline hydrolysis and by simulated gastrointestinal digestion. The action of Alcalase and digestive enzymes resulted in an increase of the antioxidant capacity of whole and phenolic reduced products. Principal component analysis showed that proteinaceous samples act as antioxidant is by H transfer, while those samples containing phenolic compounds exert their effects by both electron donation and H transfer mechanisms. Protein/peptide-phenolic complexation, confirmed by fluorescence spectra, exerted a positive effect on the antioxidant capacity, mainly in protein concentrates.This work was supported by FAPESP (2010/52680-7), CNPq and UNICAMP (FAEPEX 607-11) grants, CSIC and Ministry of Economy and Competitiveness (Ramon y Cajal contract).Peer Reviewe

Milk Proteins, Peptides, and Oligosaccharides: Effects against the 21st Century Disorders

Milk is the most complete food for mammals, as it supplies all the energy and nutrients needed for the proper growth and development of the neonate. Milk is a source of many bioactive components, which not only help meeting the nutritional requirements of the consumers, but also play a relevant role in preventing various disorders. Milk-derived proteins and peptides have the potential to act as coadjuvants in conventional therapies, addressing cardiovascular diseases, metabolic disorders, intestinal health, and chemopreventive properties. In addition to being a source of proteins and peptides, milk contains complex oligosaccharides that possess important functions related to the newborn's development and health. Some of the health benefits attributed to milk oligosaccharides include prebiotic probifidogenic effects, antiadherence of pathogenic bacteria, and immunomodulation. This review focuses on recent findings demonstrating the biological activities of milk peptides, proteins, and oligosaccharides towards the prevention of diseases of the 21st century. Processing challenges hindering large-scale production and commercialization of those bioactive compounds have been also addressed

Lunasin Peptide is a Modulator of the Immune Response in the Human Gastrointestinal Tract

[Introduction]: Lunasin is a soybean bioactive peptide with a variety of beneficial properties against chronic disorders. However, its effect in human primary intestinal cells remains unknown. Hence, this study aims to characterize its ex vivo biological activity in the human intestinal mucosa. [Methods and Results]: Human intestinal biopsies, obtained from healthy controls, are ex vivo conditioned with lunasin both in the presence/absence of lipopolysaccharide (LPS). Peptide maintains its stability during biopsy culture by HPLC-MS/MS analysis. Lunasin is bioactive in the human mucosa, as it induces IL-1β, TNF-α, IL-17A, CCL2, and PGE2/COX-2 gene expression together with an increased expression of tolerogenic IL-10 and TGFβ, while it also downregulates the expression of iNOS and subunit p65 from NF-κB. Indeed, lunasin also abrogates the LPS-induced pro-inflammatory response, downregulating IL-17A, IFNγ, and IL-8 expression, and inducing IL-10 and TGFβ expression. These results are also mirrored in the cell-free culture supernatants at the protein level by Multiplex. Moreover, lunasin further induces a regulatory phenotype and function on human intestinal conventional dendritic cell and macrophage subsets as assessed by flow cytometry. [Conclusions]: We hereby have characterized lunasin as an immunomodulatory peptide with potential capacity to prevent immune and inflammatory-mediated disorders in the human gastrointestinal tract.This work was supported by the Spanish Ministry of Economy (SAF2014-56642-JIN), the Spanish Ministry of Health (PIE13/00041), the Spanish Ministry of Science, Innovation and Universities (AGL2015-66886-R, PID2019-104218RB-I00), and the Community of Madrid (Consejería de Educación, Juventud y Deporte, Programa de Garantía Juvenil 2015 and 2016). S.F.T. is currently funded by the Instituto de Salud Carlos III (Sara Borrell fellowship CD17/00014). L.O.M. is funded by the Community of Madrid (BMD-5800). D.B. is funded by the Spanish Ministry of Science (RYC-2017-21606)