assess antioxidant capacity in vitro. However, they should be used in models based
on food and or cellular systems as it is a better approach to identify the antioxidant
potential of peptides [121]. In this perspective, the antioxidant activities of peptides
present in products derived from whey proteins can satisfy the growing demand for
more natural antioxidants to preserve human health and maintain food quality.
Corrochano et al. [126] recently reviewed the antioxidant peptides released from
whey proteins and their mechanisms on cellular antioxidant pathways.
5.6 Immunomodulatory Peptides
An increasing number of studies suggest that whey proteins may contain biologically active peptides with immunomodulatory properties encrypted in primary
sequences [127]. Theoretically, immunomodulatory peptides can be released from
whey proteins during the digestion process in the intestine and can thus affect
downstream immune responses and cellular functions. However, the amount and
concentration of bioactive peptides generated during digestion in adults are probably too low to induce significant effects on the immune system, especially for an
expected therapeutic effect. Bioactive peptide concentrates can be produced on a
commercial scale using enzymatic hydrolysis and separation technologies for their
enrichment. Additionally, the development of immunomodulatory peptides from
whey proteins is currently limited by the lack of characterization of bioactive
hydrolysate immunomodulator peptides and the absence of clinical data on the
physiological effects of these peptides. Most studies on the immunomodulatory
effects of whey proteins, enzymatic hydrolysates, and peptides have as target the
specific immune system, evaluating lymphocyte activation and proliferation,
cytokine secretion, and antibody production [128].
Wu et al. [129] identified aromatic residues and charged amino acids present in
peptide sequences of 2–12 amino acids in length as involved in binding to receptors
on the surface of cells involved in the immunologic system and production of
immune responses. For example, digestion of whey proteins with trypsinchymotrypsin demonstrated the ability to generate components involved in
immune response in a murine model of Escherichia coli infection, inducing increases
in IgA concerning the absence of infection [130]. Additionally, hydrolyzed samples
of bovine whey protein obtained with commercial enzymes, pepsin, and Corolase PP,
and using human gastric and duodenal juices, showed a dosage-dependent inhibition
in the proliferation of peripheral blood mononuclear cells in vitro. More recently, the
addition of peptides derived from whey protein showed a positive effect on the
development of immunomodulatory diets in animal models, both murine and rats
[130]. These authors identified several fragments released from b-LG with trypsin
and chymotrypsin with immunomodulatory properties such as VAGTWY f(15–20),
EILLQK f(55–60), IDALNENK f(84–91), VLVLDTDYKKYLLF f(92–105),
ALKALPMHIR f(139–148), and ALPMHIR f(142–148).
Kiewiet et al. [131] recently reviewed immunomodulatory protein hydrolysates
and their applications.
Enzymatic Production of Bioactive Peptides from Whey Proteins …
497
on food and or cellular systems as it is a better approach to identify the antioxidant
potential of peptides [121]. In this perspective, the antioxidant activities of peptides
present in products derived from whey proteins can satisfy the growing demand for
more natural antioxidants to preserve human health and maintain food quality.
Corrochano et al. [126] recently reviewed the antioxidant peptides released from
whey proteins and their mechanisms on cellular antioxidant pathways.
5.6 Immunomodulatory Peptides
An increasing number of studies suggest that whey proteins may contain biologically active peptides with immunomodulatory properties encrypted in primary
sequences [127]. Theoretically, immunomodulatory peptides can be released from
whey proteins during the digestion process in the intestine and can thus affect
downstream immune responses and cellular functions. However, the amount and
concentration of bioactive peptides generated during digestion in adults are probably too low to induce significant effects on the immune system, especially for an
expected therapeutic effect. Bioactive peptide concentrates can be produced on a
commercial scale using enzymatic hydrolysis and separation technologies for their
enrichment. Additionally, the development of immunomodulatory peptides from
whey proteins is currently limited by the lack of characterization of bioactive
hydrolysate immunomodulator peptides and the absence of clinical data on the
physiological effects of these peptides. Most studies on the immunomodulatory
effects of whey proteins, enzymatic hydrolysates, and peptides have as target the
specific immune system, evaluating lymphocyte activation and proliferation,
cytokine secretion, and antibody production [128].
Wu et al. [129] identified aromatic residues and charged amino acids present in
peptide sequences of 2–12 amino acids in length as involved in binding to receptors
on the surface of cells involved in the immunologic system and production of
immune responses. For example, digestion of whey proteins with trypsinchymotrypsin demonstrated the ability to generate components involved in
immune response in a murine model of Escherichia coli infection, inducing increases
in IgA concerning the absence of infection [130]. Additionally, hydrolyzed samples
of bovine whey protein obtained with commercial enzymes, pepsin, and Corolase PP,
and using human gastric and duodenal juices, showed a dosage-dependent inhibition
in the proliferation of peripheral blood mononuclear cells in vitro. More recently, the
addition of peptides derived from whey protein showed a positive effect on the
development of immunomodulatory diets in animal models, both murine and rats
[130]. These authors identified several fragments released from b-LG with trypsin
and chymotrypsin with immunomodulatory properties such as VAGTWY f(15–20),
EILLQK f(55–60), IDALNENK f(84–91), VLVLDTDYKKYLLF f(92–105),
ALKALPMHIR f(139–148), and ALPMHIR f(142–148).
Kiewiet et al. [131] recently reviewed immunomodulatory protein hydrolysates
and their applications.
Enzymatic Production of Bioactive Peptides from Whey Proteins …
497