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Earlier studies reported that administration of prebiotics may prevent allergic inflammation, however, results remain controversial. The aim of this study was to evaluate the effects of isomaltodextrin (IMD) against hen egg ovalbumin (OVA)-induced allergic response in mice. BALB/c mice were sensitized to OVA and subsequently administered different doses of IMD in drinking water. Our results showed that IMD supplementation led to significantly milder clinical signs and lower histamine levels in serum. Interestingly, administration of IMD did not affect serum OVA-specific IgE concentration, but led to lower total IgE titers, suggesting that the therapeutic effect of IMD may be due to immune tolerance to OVA allergen. Differences in the immune response was observed in the IMD intervention groups by lower production of IL-4. Our study suggests that the oral administration of IMD effectively attenuated OVA-induced allergic immune response in mice.

The aim of this study was to evaluate the effects of Rubus suavissimus S. Lee extract against hen egg ovalbumin (OVA)-induced allergic response in mice. BALB/c mice were sensitized with OVA via intraperitoneal injection for four weeks and subsequently administered the different doses of Rubus suavissimus S. Lee extract (0.1 0.5 and 1.0% w/v) in drinking water. We demonstrated that Rubus suavissimus S. Lee extract can attenuate OVA allergic response in mice by inducing immune desensitization through Th1/Th2 immunological modulation, a regulatory response involving the transcription factor FOXP3, induction of a suppressed IL-4, but increased IL-10, IL12a and INF-γ, enhanced immunoglobulin isotype IgA production, and suppression of histamine and MMCPT-1. These results suggest that Rubus suavissimus S. Lee extract may be a potentially useful candidate for the design of a functional food component in targeting management of food allergy.

To improve the activity of the isoflavone daidzein (1) and to explore its structure-activity relationship, new daidzein sulfonic acid ester derivatives (2–4) were synthesized. All three derivatives showed significantly enhanced anti-inflammatory activities by 100–10,000-fold over that of the parent daidzein in TNF-α-stimulated Caco-2 cells. Daidzein derivatives 2 and 3 showed the same anti-inflammatory effect at 1 μM and derivative 4 had at 0.01 μM as 100 μM daidzein. Compound 3 also showed significant anti-oxidative effect at 100 μM in H2O2-treated caco-2 cells. Treatment with daidzein and its derivatives significantly inhibited TNF-α-induced phosphorylation of JNK. Results suggest that sulfonic acid esterification at 4′- and/or 7- position of daidzein can significantly improve its physicochemical and pharmaceutical properties, consequently the cellular uptake or absorption and ultimately the biological activities.

It has previously demonstrated that adenine (6-amino-6H-purine) exhibited a vasoactive effect in contracted aorta. The adenine receptor (AdeR) has recently been identified as a G protein coupled purinergic receptor in diverse organs. It has been suggested that adenine acts as a signaling molecule through the activation of AdeR. The present study investigated the effect of adenine on endotoxin-stimulated mouse macrophages (RAW 264.7 cells) and focused on the AdeR signaling pathway. RAW 264.7 cells were treated with adenine and stimulated with lipopolysaccharide (LPS, Toll-like receptor 4 agonist) from Escherichia coli. Adenine inhibited tumor necrosis factor (TNF)-α secretion in RAW 264.7 cells. The inhibition by adenine was significantly attenuated in the presence of either adenyl cyclase (AC) or protein kinase A (PKA) inhibitors. Furthermore, adenine restored AdeR gene expression. These results firstly demonstrated that adenine acts as an anti-endotoxin compounds through a AdeR/AC/PKA signaling cascade.

Chronic exposure to low-dose of endotoxin triggers a pronounced inflammatory responses impairing gut physical barrier and resulting in microbiota dysbiosis. In this study, we investigated the anti-inflammatory activity of dietary heat killed (HK) Lactobacillus pentosus S-PT84 in a lipopolysaccharides (LPS)-induced low-grade chronic inflammation C57BL/6J mouse model. The results showed that the deficient expression of tight junction proteins (ZO-1, Cldn 3 and JAMA) and mucin 2 were restored by HK L. pentosus S-PT84. Subsequently, HK L. pentosus S-PT84 attenuated the secretion of pro-inflammatory mediators (TNF-α and MCP-1) and the decreased levels of adiponectin with a reduction in macrophage infiltration in white adipose tissue (WAT). Moreover, the dysfunctional metabolic activity observed in WAT was significantly inhibited through upregulation of PPAR-γ and IRS-1 expression. The dysbiosis in gut microbiota were prevented by HK L. pentosus S-PT84. These findings suggest that HK L. pentosus S-PT84 exerts protective effects on intestinal mucosal integrity and an early risk for progression into metabolic disorders.

A dietary peptide γ-glutamyl valine (EV) possesses the agonistic property to activate a calcium-sensing receptor-mediated anti-inflammatory pathway, thereby suppressing inflammation. This study aims to substantiate the therapeutic efficacy of γ-EV as an anti-inflammatory agent in a dextran sodium sulphate (DSS)-induced colitis porcine model. Colitis symptoms were observed after intra-gastric infusion of DSS for five days, followed by five days of administration of saline or γ-EV. γ-EV supplementation reduced DSS-induced weight loss and clinical signs, while preserving colonic architecture and intestinal permeability. Colonic production of tumour necrosis factor (TNF)-α and interleukin (IL)-6 were reduced to a level observed in animals without DSS treatment. The colonic gene expression of TNF-α, IL-6, IL-1β and interferon (IFN)-γ were also mitigated by γ-EV treatment, thus indicating γ-EV can restore immune homeostasis by attenuating inflammation. Our findings suggest that γ-EV supplementation may be a promising therapeutic strategy in the treatment of intestinal inflammation.

The antioxidant and anti-inflammatory activities of the novel pyranoanthocyanins and other polyphenols from staghorn sumac (Rhus hirta L.) were examined. The results not only confirmed the previously found antioxidant activity by chemical based assays, but more importantly strong anti-inflammatory activity for the first time in cell-based assays. These unique compounds significantly inhibited the production of pro-inflammatory cytokine IL-8 production stimulated by H2O2 and TNF-α. It was also found that these activities of the crude extract were primarily from the individual polyphenols, particularly the unique pyranoanthocyanins and 7-methoxyanthocyanins. Pyranoanthocyanin 1, in particular, showed a markedly strong anti-inflammatory activity at 1 M, followed by pyranoanthocyanin 2 and a 7-methoxyanthocyanin 5. Further mechanism investigation showed that the anti-inflammatory activity was likely mediated through inhibition of NF-κB activation via phosphorylation of IκBα. Results from the present study warrant further investigation into the in vivo anti-inflammatory effect and health benefits using animal models or human subjects.

The conformational epitopes of egg glycoproteins ovalbumin (OVA) and ovomucoid (OVM) recognized by IgE antibodies in an allergic response can be denatured at high temperatures. This structural change results in a decreased allergenicity and has earlier been used to induce clinical tolerance for specific oral immunotherapy in allergic patients via consumption of cooked egg products. We investigated the difference in allergic response when consuming heat-treated and native egg proteins by examining the cytokine production of CD4+ T cells and mast cell histamine release. Cultures of mouse CD4+ T cells and dendritic cells were stimulated with native and heat denatured OVA and OVM (HD-OVA and HD-OVM) and various cytokine and histamine concentrations were measured using ELISA. An increased concentration of IL-12, IL-17 and IL-10 and a decreased concentration of IL-4 were detected in both HD-OVA and HD-OVM (p

Excess reactive oxygen species (ROS) cause oxidative stress that is associated with the development of oxidative damage and chronic inflammation. The objective of this study was to evaluate the bioactivity of eggshell membrane (ESM) peptides digested with Alcalase and Protease S (AL-PS) at the cellular level. Effects were tested for inhibition of lipid and protein oxidation, synthesis of glutathione (GSH), and cellular antioxidant enzyme activity in H2O2-stimulated Caco-2 cells. AL-PS and its ultrafiltered fraction AL-PS-I (MWCO

Eggshell membrane (ESM) hydrolysate was prepared by Alcalase and Protease S (AL-PS) sequentially and was ultrafiltered as fractions AL-PS-I (10 kDa). The antioxidant activity of ESM hydrolysate was evaluated using chemical assays and its protective ability against oxidative stress was investigated using human intestinal epithelial Caco-2 cell-based assay. AL-PS-I possessed the highest scavenging activity against DPPH and hydroxyl radicals. AL-PS-III demonstrated the best Fe2+ chelating activity. AL-PS and AL-PS-I had higher cellular antioxidant activity to inhibit the formation of DCF. The secretion of IL-8 was inhibited significantly (P < 0.05) at 2 h post pretreatment with AL-PS, AL-PS-I and AL-PS-II (0.1 and 0.5 mg/mL) and at 6 h post stimulation with 1 mM H2O2. In addition, AL-PS, AL-PS-I and AL-PS-II (0.5 mg/mL) increased glutathione (GSH) level significantly (P < 0.05) in H2O2-treated Caco-2 cells.

Background: Nutritional prebiotic supplementation represents an attractive approach for interventions of allergy. In this study, the potential therapeutic effect of β-1, 4 mannobiose (MNB) in a murine model of cedar polli- nosis 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-β 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-β 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.

Background: Dietary supplementation with unique prebiotic nondigestible carbohydrates has been shown to suppress allergy. In the present study, the prophylactic efficacy of a disaccharide p-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 (P0.05). The MNB-treated mice had increased IFN-y (P0.05). 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

In order to investigate the anti-inflammatory activity of egg yolk-derived phosphopeptides (PPPs), intestinal epithelial (Caco-2 cells, HT-29 cells) and macrophage RAW 264.7 cell lineages were stimulated with either tumor necrosis factor alpha (TNF-α) or Salmonella enterica lipopolysaccharide (LPS). Upon pre-incubation with different doses of PPPs, the secretion of interleukin 8 (IL-8) and TNF-α in cell supernatants was quantified by enzyme-linked immunosorbent assay (ELISA). The gene expression levels of inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines (i.e., IL-8, IL-12, IL-6, monocyte chemoattractant protein-1 (MCP-1), TNF-α, IL-1β) were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results revealed that PPPs significantly inhibit the secretion of IL-8 in TNF-α-stimulated Caco-2 and HT-29 cells in a dose-dependent manner; while no significant difference was observed in LPS-stimulated Caco-2 and HT-29 cells. Interestingly, the expression of IL-8, MCP-1 and IL-12 was inhibited by PPPs in both TNF-α- and LPS-stimulated HT-29 cells, and similarly, the expression of TNF-α, IL-1β, IL-6, and iNOS was downregulated significantly in LPS-stimulated macrophage RAW 264.7 cells pre-incubated with PPPs. We conclude that PPPs possesses anti-inflammatory properties evidenced by the down-regulation of key pro-inflammatory markers. Thus our results suggest that PPPs may serve as nutraceutical compounds with anti-inflammatory properties.

The anti-allergic immunomodulatory effects of Quillaja saponin in antigen-stimulated rat basophilic leukemia cell line RBL-2H3 were investigated. Quillaja saponin exhibited a significant inhibitory activity using β-hexosaminidase and histamine release assays on anti-DNP-IgE-sensitized rat basophilic leukemia (RBL)-2H3 cells in a dose-dependent manner when tested in the range of 0.5–8.0 μg/mL. In addition, Quillaja saponin also suppressed mRNA expression of interleukins (IL)-4 and IL-6. In order to explore the antigen-allergy mechanisms of Quillaja saponin in mast cells, intracellular Ca2+ level and IgE receptor FcεRI mRNA expression were also determined. It was found that the intracellular Ca2+ level was also decreased with Quillaja saponin tested at various concentrations. Furthermore, real time-PCR results showed that mRNA expression of FcεRI α chain was significantly suppressed by Quillaja saponin, and not of the β and γ chains.

Inflammatory bowel disease (IBD) is a chronic and recurring inflammation of the gastrointestinal tract; however, current pharmaceutical treatments are only moderately effective and have potential long-term toxicity, therefore novel IBD therapies are required. Hen egg white has been shown to be an abundant source of novel immunomodulating proteins and peptides. The anti-inflammatory activity of egg white peptides was examined using a porcine model of dextran sodium sulphate (DSS)-induced colitis. DSS was administered for five days via intra-gastric catheter to induce experimental colitis, followed by five days of treatment with egg white peptides (EWP) or saline.Supplementation with EWP attenuated the DSS-induced clinical symptoms, including weight loss, mucosal and submucosal inflammation, crypt distortion, and colon muscle thickening, and restored gut barrier function by decreasing intestinal permeability and increasing mucin gene expression. Furthermore, treatment with EWP significantly reduced the local expression of pro-inflammatory cytokines TNF-α, IL-6, IL-1β, IFN-γ, IL-8, and IL-17, suggesting that EWP is a promising novel therapeutic for the treatment of IBD.