Improvement of memory function via a combination of exercise and soy peptide supplementation in community-dwelling older adults: A randomized controlled trial.

Background: Soy peptide, when consumed as a functional food, has been reported to improve cognitive function. This study aimed to verify the combined effect of soy peptide supplementation and exercise on cognitive function among community-dwelling older adults in Japan. Methods: In this population-based, non-blinded randomized controlled trial, 72 community-dwelling older adults who were independent in activities of daily living were randomly assigned to an "exercise plus nutrition" program (Ex + Nt group, n = 36) or an exercise program (Ex group, n = 36). For 3 months, both groups participated in an exercise and cognitive training regimen once per week, with the Ex + Nt group receiving soy supplementation once per week. Pre- and post-intervention measurements included grip strength, gait speed, skeletal muscle mass index, and scores on Addenbrooke's Cognitive Examination-Revised, trail-making test A, and the Geriatric Depression Scale. Participant enrollment for this study started in January 2019 and ended in April 2019. Results: Exercise training increased the skeletal muscle mass index by 2.0% and 3.0% in the Ex + Nt and Ex groups, respectively. The Ex + Nt group exhibited a significant 0.3-point increase in the memory score. Conclusion: A 3-month exercise program combined with soy peptide supplementation may be effective in improving both motor and memory function in community-dwelling older adults.

Effect of Multicomponent Exercise and Nutrition Support on the Cognitive Function of Older Adults: A Randomized Controlled Trial.

PURPOSE: This study compared the effects of a combination of soy peptide supplementation and exercise with those of exercise only, on the cognitive function of elderly adults. PATIENTS AND METHODS: This randomized, non-blinded, controlled clinical trial included 67 participants aged 60 years or more with non-cognitive dysfunction who were divided into two groups according to the intervention method: an exercise group (Ex group, n = 36) and an exercise plus nutrition group (Ex+Nt group, n = 31). The Ex group completed a memory training activity for 15 mins and aerobic exercise for 45 mins once a week for 90 days. The Ex+Nt group completed the same training plus received soy peptide for 90 days. The Mini-Mental Status Examination score, trail-making test A/B score, skeletal muscle mass index, grip strength, gait speed, and geriatric depression scale were measured at baseline and post intervention. For comparison between the pretest and posttest measurements to determine the intervention effects, a two-way analysis of variance was performed. The significance level was set at < 5%. RESULTS: A two-way analysis of variance revealed significant time effects on trail-making test-A score, skeletal muscle index, grip strength, and gait speed in both groups. There were significant time x group interactions for greater increase in calculation score. CONCLUSION: A combination of exercise and soy peptide supplementation was effective in improving a portion of cognitive function.

Enhancement of immune response and resistance against Vibrio parahaemolyticus in kuruma shrimp (Marsupenaeus japonicus) by dietary supplementation of ß-1,4-mannobiose.

Supplementation of prebiotic carbohydrates can act as a potent immunomodulator and have the efficacy to induce immune-related genes which are involved in host defense. Pure ß-1,4-mannobiose (MNB) showed activation of prophenoloxidase system of shrimp hemocytes in vitro. The resistance of kuruma shrimp Marsupenaeus japonicus against Vibrio parahaemolyticus was examined after the shrimp were fed with 0 (control), 0.02, 0.2, and 2% MNB supplemented diets. The results showed significantly higher survival rates in MNB supplemented shrimp than those of the control one from 2 to 12 days post challenge. In another experiment, the hemocyte count, ROS production, phagocytic, phenoloxidase and bactericidal activities, and expression of immune-related genes were investigated in the control and MNB supplemented groups at day 1, 4, 6, 8 and 11 of the feeding. These immune parameters were significantly enhanced in MNB supplemented groups. Furthermore, the gene expression analysis showed that transcripts of lysozyme, crustin, penaeidin and TNF were significantly up-regulated in hemolymph, lymphoid organs and intestines of MNB treated shrimp. Overall, the results provided evidence that MNB supplementation could improve the immune response and increase shrimp resistance against V. parahaemolyticus infection.

Dietary mannanase-hydrolyzed copra meal improves growth and increases muscle weights in growing broiler chickens.

The utilization of copra meal as a feed ingredient is limited because it contains a high level of mannan. However, recent findings indicate that the effect of copra meal on growth performance in broiler chickens can be improved by the supplementation of mannanase in the diet. In the present study, we examined the effect of mannanase-hydrolyzed copra meal (MCM) on growth performance and muscle protein metabolism in growing broiler chickens (Gallus gallus domesticus). Forty 8-day-old male broiler chicks were assigned to two groups (four birds in each pen, five replicates) and fed either a commercial diet (as a control diet) or a diet containing MCM at 0.2% until 22 days of age. Dietary MCM significantly increased the weights of body, breast muscle, and thighs in chickens, whereas the weights of abdominal adipose tissue and liver were not affected. Cumulative feed intake was significantly increased by MCM. Dietary MCM significantly decreased plasma 3-methylhistidine level. The messenger RNA and protein levels of muscle protein metabolism-related factors were not altered by MCM. These findings suggest that the growth-promoting effect of MCM is related to the suppression of muscle proteolysis in growing broiler chickens.

Anti-inflammatory effects of mannanase-hydrolyzed copra meal in a porcine model of colitis.

We evaluated the anti-inflammatory activity of mannanase-hydrolyzed copra meal (MNB), including ß-1,4-mannobiose (67.8%), in a dextran sodium sulfate (DSS)-induced porcine model of intestinal inflammation. In the DSS-positive control (POS) and MNB treatment (MCM) groups, DSS was first administered to piglets via intragastric catheter for 5 days, followed by 5 days administration of saline or MCM. A negative control group (NEG) received a saline alternative to DSS and MNB. Inflammation was assessed by clinical signs, morphological and histological measurements, gut permeability and neutrophil infiltration. Local production of TNF-α and IL-6 were analyzed by ELISA, colonic and ileal inflammatory gene expressions were assessed by real time RT-PCR, and CD4+CD25+ cell populations were analyzed by flow cytometry. Crypt elongation and muscle thickness, D-mannitol gut permeation, colonic expression of the inflammatory mediators TNF-α and IL-6 and myeloperoxidase activity were significantly lower in the MCM group than in that of POS group. The mRNA levels of ileal IL-1ß, IL-6, IL-17 and TNF-α were significantly lower following MCM treatment than with POS treatment.MNB exerts anti-inflammatory activity in vivo, suggesting that MNB is a novel therapeutic that may provide relief to human and animals suffering from intestinal inflammation.

ß-1,4-mannobiose stimulates innate immune responses and induces TLR4-dependent activation of mouse macrophages but reduces severity of inflammation during endotoxemia in mice.

ß-1,4-Mannobiose (MNB) has been shown to exert prebiotic activity and modulate mucosal gene expression. In this study, the immune-modulating effect of MNB in healthy and endotoxemic mice and its role in Toll-like receptor (TLR) 2/4-mediated macrophage activation were investigated. Mice were supplemented daily with MNB (0, 5, 10, or 25 mg/kg) for 14 d. To examine the effect of MNB during endotoxemia, mice were supplemented with or without MNB (25 mg/kg) for 14 d, followed by challenge with intraperitoneal LPS or saline. MNB induced expression of both T helper (Th) 1- and Th2-type cytokines in the ileum (P < 0.05) and increased fecal IgA production and splenic NK cell activity (P < 0.05) in healthy mice. In endotoxemic mice, MNB reduced the expression of Tnfa, Il-6, iNos (P < 0.05), and Il-10 (P < 0.05), and reduced LPS-induced weight loss but increased Ifng, Il-12p40, Il-5, and Ifna expression (P < 0.05) and NK cell activity relative to positive control (LPS) mice. Treatment of RAW 264.7 macrophages with MNB induced TNF-α and IL-6 secretion (P < 0.05), and this effect was abrogated by inhibiting TLR4, but not TLR2, signaling. Pretreatment of RAW 264.7 cells with MNB induced tolerance to TLR2 and TLR4 agonists, reducing TNF-α production (P < 0.05) upon secondary stimulation with LPS or lipoteichoic acid. These results indicate that MNB can modulate intestinal and systemic immune responses in healthy and endotoxemic mice and prevent LPS-induced immune suppression, as well as directly stimulating innate immune mechanisms in vitro as a TLR4 agonist.

Prophylaxis of intranasally induced pollen allergy in a BALB/C mouse model using a potential prebiotic ß-1, 4 mannobiose.

BACKGROUND: Dietary supplementation with unique prebiotic nondigestible carbohydrates has been shown to suppress allergy. In the present study, the prophylactic efficacy of a disaccharide ß-1, 4 mannobiose (MNB) in a BALB/C mouse model of intranasally-induced pollen allergy was characterized. METHODS: Balb/c mice were pretreated with MNB orally and sensitized with pollen extract intraperitoneally and intranasally and challenged with histamine and crude pollen extract. Outcomes were measured as clinical signs, antibody isotypes, cytokine gene and protein expression patterns. RESULTS: The MNB-treated mice had lower sneezing frequency as compared to the positive control mice (P < 0.05). The low dose MNB-treated mice had less histamine (P < 0.05). However, the Cry j1 and Cry j 2-specific IgE, IgG, IgG1 and IgG2a antibody activity did not differ between groups (P > 0.05). The MNB-treated mice had increased IFN-γ (P < 0.05), and decreased IL-4 (P < 0.05). Mice in the high dose group had increased IL-10 (P < 0.05). However, TGF-ß and IL-17 concentration did not differ between groups (P > 0.05). Both total and Cry j1 and Cry j 2-specific IgA were increased in the high dose group. Real-time RT-PCR analysis indicated that IL-4 and IL-17 mRNA expression were lower in MNB-treated mice (P < 0.05). CONCLUSIONS: This work provides insights into using MNB as a potential prebiotic immunomodulator via decreased clinical signs, improved type1/type 2 balance, and IgA production, thus validating the potential use of MNB as a prophylactic prebiotic candidate to attenuate allergic response.

Therapeutic effects of ß1, 4 mannobiose in a Balb/c mouse model of intranasally-induced pollen allergy.

BACKGROUND: Nutritional prebiotic supplementation represents an attractive approach for interventions of allergy. In this study, the potential therapeutic effect of ß-1, 4 mannobiose (MNB) in a murine model of cedar pollinosis was investigated. METHODS: Groups of Balb/c mice were intranasally sensitized to Japanese cedar pollen extract, and subsequently administered with low or high dose MNB. Both intraperitoneal and intranasal challenges were performed to monitor for clinical signs. Frequency of sneezing was recorded. Serum, spleen and Peyer's patches were collected for various biomarker analyses. Anti-allergic activity of MNB using RBL-2H3 cells was also evaluated. RESULTS: Significant decrease in sneezing frequency, histamine, interleukin (IL)-4 and IL-17A and increase in TGF-ß and IL-10 concentration were exhibited by the MNB-treated mice. However, Cry j1 and Cry j 2-specific IgE activity remained unaltered. The high dose MNB treatment increased total IgA activity and IL-10, TGF-ß and FoxP3 and decreased IL-4, IL-17A, and RORγT mRNA expression. Inhibition of activation of RBL-2H3 cells was observed via decrease in histamine, intracellular Ca2+ concentration, and FcεRI mRNA expression. CONCLUSIONS: We demonstrated the immunomodulatory effects of MNB and conclude that MNB is a potential therapeutic molecular nutritional supplement candidate for treatment of pollen allergy.

The PepT1-transportable soy tripeptide VPY reduces intestinal inflammation.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract. The peptide transporter PepT1 is responsible for the intestinal uptake of dietary peptides, and its expression in the gastrointestinal tract is up-regulated during intestinal inflammation, indicating that PepT1 may be a promising target for IBD therapeutics. METHODS: The transport of soy-derived di- and tripeptides across Caco-2 intestinal epithelial cells was examined, and the anti-inflammatory effects of the transported peptide VPY were evaluated in vitro in Caco-2 and THP-1 macrophages, and in vivo in a mouse model of DSS-induced colitis. RESULTS: VPY inhibited the secretion of IL-8 and TNF-α, respectively, from Caco-2 and THP-1 cells. VPY transport and anti-inflammatory activity in Caco-2 cells was reduced in the presence of Gly-Sar, indicating this activity was mediated by PepT1. In mice, VPY treatment reduced DSS-induced colitis symptoms and weight loss, improved colon histology, reduced MPO activity, and decreased gene expression of the pro-inflammatory cytokines TNF-α, IL-6, IL-1ß, IFN-γ and IL-17 in the colon. CONCLUSIONS AND GENERAL SIGNIFICANCE: VPY is a novel PepT1 substrate that can inhibit the production of pro-inflammatory mediators in vitro in intestinal epithelial and immune cells, and reduce the severity of colitis in mice by down-regulating the expression of pro-inflammatory cytokines in the colon, suggesting that VPY may be promising for the treatment of IBD.

Soy-derived di- and tripeptides alleviate colon and ileum inflammation in pigs with dextran sodium sulfate-induced colitis.

We evaluated the antiinflammatory activity of soy-derived di- and tripeptides in a dextran sodium sulfate (DSS)-induced pig model of intestinal inflammation. In the DSS-positive control (POS) and DSS-positive with soy peptide treatment (SOY) groups (n = 6/group), DSS was administered to piglets via i.g. catheter for 5 d, followed by a 5-d administration of saline or soy-derived peptides, respectively. A negative control (NEG) group received saline in lieu of the DSS and soy peptides. The severity of inflammation was assessed by clinical signs, morphological and histological measurements, gut permeability, and neutrophil infiltration. Local production of TNF and IL6 were measured by ELISA, colonic and ileal inflammatory gene expression were assessed by real-time RT-PCR, and CD4+CD25+ lymphocyte populations were analyzed by flow cytometry. Crypt elongation and muscle thickness, d-mannitol gut permeation, colonic expression of the inflammatory mediators IFNG, IL1B, TNF, RORC, and IL17A as well as the FOXP3 T-regulatory transcription factor, and myeloperoxidase activity were lower (P < 0.05) in the SOY pigs than in POS pigs. Messenger RNA levels of ileal IFNG, TNF, IL12B, and IL17A were lower (P < 0.05) and FOXP3 expression was greater (P < 0.05) in SOY piglets than in the POS group. In the mesenteric lymph nodes, CD4+CD25+ T cells were higher (P < 0.05) in both the POS and SOY groups than in NEG controls. Soy-derived peptides exert antiinflammatory activity in vivo, suggesting their usefulness for the treatment of inflammatory disorders.

ß 1-4 mannobiose enhances Salmonella-killing activity and activates innate immune responses in chicken macrophages.

Salmonella spp. is one of the major causes of food-borne illness in humans, and Salmonella enteritidis (SE) infection in commercial poultry is a world-wide problem. Here we have investigated the in vitro immune-modulating effects of ß 1-4 mannobiose (MNB), which was previously found to prevent SE infection in vivo in chickens, using chicken macrophage (MQ-MCSU) cells. Treatment of MQ-NCSU cells with MNB dose-dependently increased both phagocytic activity and Salmonella-killing activity of macrophages, with the highest reduction in SE viability observed at a concentration of 40 µg/ml at 48 h post-infection. Likewise, both hydrogen peroxide (H(2)O(2)) and nitric oxide (NO) production were increased in a dose-dependent manner by MNB. Gene expression analysis of MNB-treated macrophages revealed significant increases in the expression of iNOS, NOX-1, IFN-γ, NRAMP1, and LITAF, genes critical for host defense and antimicrobial activity, when compared to untreated cells. This data confirms that MNB possesses potent innate immune-modulating activities and can up-regulate antibacterial defenses in chicken macrophages.