Glycomacropeptide Bioactivity and Health: A Review Highlighting Action Mechanisms and Signaling Pathways

Food-derived bioactive peptides are reported as beneficial and safe for human health. Glycomacropeptide (GMP) is a milk-protein-derived peptide that, in addition to its nutritional value, retains many biological properties and has therapeutic effects in several inflammatory disorders. GMP was shown under in vitro and in vivo conditions to exert a number of activities that regulate the physiology of important body systems, namely the gastrointestinal, endocrine, and immune systems. This review represents a comprehensive compilation summarizing the current knowledge and updated information on the major biological properties associated with GMP. GMP bioactivity is addressed with special attention on mechanisms of action, signaling pathways involved, and structural characteristics implicated. In addition, the results of various studies dealing with the effects of GMP on models of inflammatory diseases are reviewed and discussed

Inhibition of Candida albicans cell growth and biofilm formation by a bioactive extract produced by soil Streptomyces strain GCAL-25

Resistance to antifungal agents is a major public health concern since multidrug resistant (MDR) strains of Candida albicans have caused severe infections among immunosuppressed, diabetic and other hospital patients. This study focused on evaluating the effects of a bioactive extract (BEx) produced by a novel Streptomyces species on C. albicans cell germination and biofilm formation. Agar disk diffusion assays were used to select a streptomycete with inhibitory activity over C. albicans cells. Thereafter, minimal inhibition concentration (MIC) and time-kill values were obtained for the BEx prepared from the isolate GCAL-25. Also, the effects of BEx on biofilm formation were analyzed. Results showed that the GCAL-25 isolate from the Streptomyces genus displayed inhibitory activity on C. albicans. A paper disk soaked with BEx showed an inhibitory halo around confluent growing cells of C. albicans. The calculated MIC values for BEx indicated that C. albicans was three times more susceptible to BEx than the control fungicide, amphotericin B (AmpB). Time-kill studies with 1/2x and 1xMIC of BEx showed severe negative effects on cell viability, suggesting a strong fungicidal activity. In addition, an important reduction of C. albicans biofilm formation was observed. The BEx from Streptomyces sp. GCAL-25 altered yeast-to-hyphae transitions and induced abnormal cell morphology (e.g. cell shrinkage), including impairments of cell membrane integrity with negative effects on biofilm formation

Protective Effect of Glycomacropeptide on Food Allergy with Gastrointestinal Manifestations in a Rat Model through Down-Regulation of Type 2 Immune Response

Glycomacropeptide (GMP) is a bioactive peptide derived from milk κ-casein with immune-modulatory and anti-inflammatory properties. Food allergy (FA) is an adverse immune reaction with a broad spectrum of manifestations. Allergen intake induces persistent intestinal inflammation and tissue damage. In this study, the anti-allergic activity of GMP was evaluated using a rat ovalbumin (OVA)-induced FA model with gastrointestinal manifestation. Rats were orally GMP treated from 3 days prior and during FA development. The severity of food anaphylaxis and diarrheal episodes, antibody production and histamine level were measured. Histopathological changes, inflammation and predominant cytokine profile at intestine were analyzed. Oral GMP intake decreased clinical signs and diarrhea severity induced by allergen, with a significant reduction in intestinal edema and expression level of IL-1β and TNF-α. Prophylaxis with GMP also diminished serum anti-OVA IgE and IgG1, and histamine levels. GMP treatment markedly decreased eosinophil infiltration, mast cell and goblet cell hyperplasia, total IgE expression in intestine, and prevented histological changes in villi, crypts and internal muscularis layer. The treatment effectively suppressed IL-5, IL-13 and GATA3 expression and skewed the intestinal cytokine profile toward type 1 and regulatory. These results suggest that GMP may protect against FA through down-regulating the type 2 inflammatory response

Glycomacropeptide Ameliorates Indomethacin-Induced Enteropathy in Rats by Modifying Intestinal Inflammation and Oxidative Stress

Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy is considered a serious and increasing clinical problem without available treatment. Glycomacropeptide (GMP) is a 64-amino acid peptide derived from milk κ-casein with numerous biological activities. The aim of this study was to investigate the protective effect of GMP on NSAID enteropathy in rats. Enteropathy was induced by seven days oral indomethacin administration. Rats were orally GMP treated from seven days previous and during the establishment of the enteropathy model. Changes in metabolism, hematological and biochemical blood alterations, intestinal inflammation and oxidative damage were analyzed. Integrity barrier markers, macroscopic intestinal damage and survival rate were also evaluated. GMP treatment prevented anorexia and weight loss in animals. Furthermore, prophylaxis with GMP ameliorated the decline in hemoglobin, hematocrit, albumin and total protein levels. The treatment had no therapeutic efficacy on the decrease of occludin and mucin (MUC)-2 expression in intestinal tissue. However, GMP markedly decreased neutrophil infiltration, and CXCL1, interleukin-1β and inducible nitric oxide synthase expression. Nitric oxide production and lipid hydroperoxide level in the small intestine were also diminished. These beneficial effects were mirrored by preventing ulcer development and increasing animal survival. These results suggest that GMP may protect against NSAID enteropathy through anti-inflammatory and antioxidant properties

Effects of a Modern Kefir on Conditions Associated with Moderate Severe Spastic Quadriparesis Cerebral Palsy

Cerebral palsy (CP) in children constitutes a set of movement and body posture disorders caused by brain injury, which in turn is associated with a series of intestinal, respiratory, and malnutrition conditions. Twenty-four children were selected and included for the present study and subdivided into two groups: (1) children who included modern kefir (containing 12 probiotic species) in their diet; and (2) control group (not including kefir in their diet). The group supplemented with modern kefir received a beverage with multi probiotic species and the control group received commercial yogurt (which included the 2 typical lactic acid bacteria) for 7 weeks. Anthropometric variables, resting energy expenditure, presence, and diagnosis of functional digestive disorders (FDD), frequency of respiratory problems, presence of elevated C-reactive protein, differential count of leukocytes were evaluated. A significant increase in weight and height was found in the kefir group at the final time point. In addition, kefir intake promoted a significant reduction in functional constipation and stool hardness and increased the absolute value of blood lymphocytes. Since the fermented milk beverage modern kefir improves constipation, which is the most important FDD in children with CP and the nutritional and immune status, it could be considered an important strategy to improve health in these children