BIOFUNCTIONALITY AND IMMUNOMODULATORY MECHANISMS OF ACTIVE PROTEINS AND CYTOKINES: A REVIEW OF STRUCTURE, PHYSICOCHEMICAL PROPERTIES, AND IMPACTS ON HUMAN HEALTH
DOI:
https://doi.org/10.63330/aurumpub.019-013Keywords:
Bioactive proteins, Cytokines, Immunomodulation, NutraceuticalsAbstract
Active proteins and bioactive peptides have attracted increasing scientific interest due to their properties that go beyond basic nutritional value, exerting specific physiological effects with direct impacts on human health. This review compiles and discusses current evidence on the biofunctionality and immunomodulatory mechanisms of active proteins and cytokines, with emphasis on their structural characteristics, physicochemical properties, and biological functions. Fundamental concepts related to the definition, origin, and release of bioactive peptides are addressed, as well as the influence of molecular structure on biological activity. The role of specific proteins is highlighted, particularly immunoglobulins (IgM, IgA, and IgG), lactoferrin, lactoperoxidase, beta-lactoglobulin, alpha-lactalbumin, lysozyme, and bovine serum albumin, which are recognized for their antimicrobial, antioxidant, antihypertensive, anticancer, and immunomodulatory activities. In addition, this review explores the role of cytokines as essential bioactive proteins in immune regulation, with emphasis on interleukins (IL-1β, IL-6, IL-8, and IL-10), tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β), and interferon gamma (IFN-γ), particularly in the context of milk and colostrum. Overall, the findings highlight the potential of these molecules for the development of functional foods, nutraceuticals, and therapeutic strategies aimed at promoting health and preventing disease.
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References
ABBAS, A.K., LICHTMAN, A.H., E PILLAI, S. Cellular and Molecular Immunology - 10th Edition | Elsevier Shop. [S.l.: S.n.].
AL SHAREEF, Rolan et al. Can artificial intelligence uncover the bioactive peptides’ benefits for human health and knowledge? A narrative review. Frontiers in Nutrition, v. 12, p. 1698147, 15 dez. 2025. Bioactive Components. [S.l.: S.n.].
BRANDTZAEG, Per. The mucosal immune system and its integration with the mammary glands. The Journal of pediatrics, v. 156, n. 2 Suppl, p. S8, 2010.
BROGDEN, Kim A. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nature Reviews Microbiology, v. 3, n. 3, p. 238–250, mar. 2005.
BUTLER, John E. Bovine Immunoglobulins: A Review. Journal of Dairy Science, v. 52, n. 12, p. 1895–1909, 1 dez. 1969.
DALIRI, Eric; OH, Deog; LEE, Byong. Bioactive Peptides. Foods, v. 6, n. 5, p. 32, 26 abr. 2017.
DINARELLO, Charles A. Historical insights into cytokines. European Journal of Immunology, v. 37, n. S1, p. S34–S45, nov. 2007.
DONG, Yufan et al. Regulatory Potential of Food-Derived Bioactive Peptides on Gut Microbiota: A New Perspective against Immune-Mediated Inflammatory Diseases. Journal of Agricultural and Food Chemistry, v. 73, n. 28, p. 17403–17416, jul. 2025.
ELAGAMY, E. I. et al. Purification and characterization of lactoferrin, lactoperoxidase, lysozyme and immunoglobulins from camel’s milk. International Dairy Journal, v. 6, n. 2, p. 129–145, 1996.
GARCÍA-MONTOYA, Isui Abril et al. Lactoferrin a multiple bioactive protein: An overview. Biochimica et Biophysica Acta (BBA) - General Subjects, v. 1820, n. 3, p. 226–236, mar. 2012.
GAROFALO, Roberto P.; GOLDMAN, Armond S. Cytokines, chemokines, and colony-stimulating factors in human milk: the 1997 update. Biology of the neonate, v. 74, n. 2, p. 134–142, ago. 1998.
H., Meisel; J., FitzGerald. Biofunctional Peptides from Milk Proteins: Mineral Binding and Cytomodulatory Effects. Current Pharmaceutical Design, v. 9, n. 16, p. 1289–1295, 1 jun. 2003.
HANCOCK, Robert E. W.; SAHL, Hans-Georg. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nature Biotechnology, v. 24, n. 12, p. 1551–1557, 11 dez. 2006.
HARAGUCHI, Fabiano Kenji; DE ABREU, Wilson César; DE PAULA, Heberth. Proteínas do soro do leite: composição, propriedades nutricionais, aplicações no esporte e benefícios para a saúde humana. Revista de Nutrição, v. 19, n. 4, p. 479–488, 2006.
HILL, Colin et al. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nature Reviews Gastroenterology & Hepatology, v. 11, n. 8, p. 506–514, 10 ago. 2014.
IBIETA, Gabriela et al. Bioactive peptides as functional food ingredients: Production, mechanisms of action, market trends, and future perspectives with emphasis on andean crops. Journal of Functional Foods, v. 135, p. 107109, 1 dez. 2025.
KIELBASA, Anna; GADZALA-KOPCIUCH, Renata; BUSZEWSKI, Boguslaw. Cytokines-Biogenesis and Their Role in Human Breast Milk and Determination. International Journal of Molecular Sciences, v. 22, n. 12, p. 6238, 2 jun. 2021.
KONTOPIDIS, G.; HOLT, C.; SAWYER, L. Invited Review: β-Lactoglobulin: Binding Properties, Structure, and Function. Journal of Dairy Science, v. 87, n. 4, p. 785–796, abr. 2004.
KORHONEN, Hannu. Milk-derived bioactive peptides: From science to applications. Journal of Functional Foods, v. 1, n. 2, p. 177–187, abr. 2009.
KORHONEN, Hannu; PIHLANTO, Anne. Bioactive peptides: Production and functionality. International Dairy Journal, v. 16, n. 9, p. 945–960, set. 2006.
KUSSENDRAGER, Klaas D.; VAN HOOIJDONK, A. C. M. Lactoperoxidase: physico-chemical properties, occurrence, mechanism of action and applications. British Journal of Nutrition, v. 84, n. S1, p. 19–25, 9 nov. 2000.
LKHAGVASUREN, Enkhhsaikhan. Janeway’s Immunobiology, 9th Edition. Central Asian Journal of Medical Sciences, v. 3, n. 1, p. 100–101, 25 fev. 2017.
MOHANTY, D. P. et al. Milk derived bioactive peptides and their impact on human health – A review. Saudi Journal of Biological Sciences, v. 23, n. 5, p. 577–583, set. 2016.
MUTHUKUMARAN, M. Selva et al. A comprehensive review on health benefits, nutritional composition and processed products of camel milk. Food Reviews International, v. 39, n. 6, p. 3080–3116, 2023.
NAGPAL, Ravinder et al. Gut microbiome and aging: Physiological and mechanistic insights. Nutrition and Healthy Aging, v. 4, n. 4, p. 267–285, 15 jun. 2018.
ÖZHAN, Hasan Kutluay et al. Lactoperoxidase: Properties, Functions, and Potential Applications. International journal of molecular sciences, v. 26, n. 11, 1 jun. 2025.
PALMEIRA, Patricia et al. IgG Placental Transfer in Healthy and Pathological Pregnancies. Clinical and Developmental Immunology, v. 2012, p. 1–13, 2012.
PEREIRA, A. S. et al. Metodologia de Pesquisa Científica. 1a ed. ed. Santa Maria: Universidade Federal de Santa Maria, 2018.
PERMYAKOV, Eugene A.; BERLINER, Lawrence J. α‐Lactalbumin: structure and function. FEBS Letters, v. 473, n. 3, p. 269–274, 19 maio 2000.
PLAYFORD, R. J. et al. Bovine colostrum is a health food supplement which prevents NSAID induced gut damage. Gut, v. 44, n. 5, p. 653–658, 1 maio 1999.
POWER, O.; JAKEMAN, P.; FITZGERALD, R. J. Antioxidative peptides: enzymatic production, in vitro and in vivo antioxidant activity and potential applications of milk-derived antioxidative peptides. Amino Acids, v. 44, n. 3, p. 797–820, 12 mar. 2013.
RAGLAND, Stephanie A.; CRISS, Alison K. From bacterial killing to immune modulation: Recent insights into the functions of lysozyme. PLOS Pathogens, v. 13, n. 9, p. e1006512, 21 set. 2017.
ROBERFROID, Marcel et al. Prebiotic effects: metabolic and health benefits. British Journal of Nutrition, v. 104, n. S2, p. S1–S63, 1 ago. 2010.
RUIZ, Lorena; FERNÁNDEZ, Leónides; RODRÍGUEZ, Juan M. Immune factors in human milk. Human Milk: Sampling and Measurement of Energy-Yielding Nutrients and Other Macromolecules, p. 275–298, 1 jan. 2021.
SÁNCHEZ, Adrián; VÁZQUEZ, Alfredo. Bioactive peptides: A review. Food Quality and Safety, v. 1, n. 1, p. 29–46, 1 mar. 2017.
SEIFU, Eyassu; BUYS, Elna M.; DONKIN, E. F. Significance of the lactoperoxidase system in the dairy industry and its potential applications: a review. Trends in Food Science & Technology, v. 16, n. 4, p. 137–154, abr. 2005.
SUPERTI, Fabiana. Lactoferrin from Bovine Milk: A Protective Companion for Life. Nutrients, v. 12, n. 9, p. 2562, 24 ago. 2020.
SVENSSON, M. et al. Conversion of α-lactalbumin to a protein inducing apoptosis. Proceedings of the National Academy of Sciences, v. 97, n. 8, p. 4221–4226, 11 abr. 2000.
TULIPANO, Giovanni. Role of Bioactive Peptide Sequences in the Potential Impact of Dairy Protein Intake on Metabolic Health. International Journal of Molecular Sciences, v. 21, n. 22, p. 8881, nov. 2020.
UDENIGWE, Chibuike C.; ALUKO, Rotimi E. Food Protein‐Derived Bioactive Peptides: Production, Processing, and Potential Health Benefits. Journal of Food Science, v. 77, n. 1, 10 jan. 2012.
WALSTRA, P. et al. Dairy Science and Technology. [S.l.]: CRC Press, 2005.
ZAKY, Ahmed A. et al. Bioactivities, Applications, Safety, and Health Benefits of Bioactive Peptides From Food and By-Products: A Review. Frontiers in nutrition, v. 8, 20 jan. 2022.
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