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Traditional Chinese preserved egg products have exhibited some anti-inflammatory effects, but their mechanisms of action remain unknown. This study aimed to investigate the anti-inflammatory effects of preserved egg white (PEW) treatment on dextran sulfate sodium (DSS)-induced colitis in mice and the underlying mechanisms. The results showed that treatment with PEW in mice with DSS-induced colitis for 14 days effectively improved the clinical signs, inhibited the secretion and gene expression of pro-inflammatory cytokines, and reduced myeloperoxidase (MPO) activity and oxidative stress levels. In addition, western blotting results showed that PEW significantly suppressed DSS-induced phosphorylation levels of nuclear factor-kappa B (NF-κB) p65 and p38 mitogen-activated protein kinase (MAPK) in colon tissues of mice with colitis. PEW also enhanced the production of short-chain fatty acids (SCFAs) and modulated gut microbiota composition in mice with DSS-induced colitis, including increasing the relative abundance of beneficial bacteria Lachnospiraceae, Ruminococcaceae and Muribaculaceae, and reducing the relative abundance of harmful bacteria Proteobacteria. Taken together, our study demonstrated that preserved egg white could alleviate DSS-induced colitis in mice through the reduction of oxidative stress, modulation of inflammatory cytokines, NF-κB, MAPK and gut microbiota composition.

Gut alkaline phosphatases (AP) dephosphorylate the lipid moiety of endotoxin and other pathogen-associated-molecular patterns members, thus maintaining gut eubiosis and preventing metabolic endotoxemia. Early weaned pigs experience gut dysbiosis, enteric diseases and growth retardation in association with decreased intestinal AP functionality. However, the role of glycosylation in modulation of the weaned porcine gut AP functionality is unclear. Herein three different research approaches were taken to investigate how deglycosylation affected weaned porcine gut AP activity kinetics. In the first approach, weaned porcine jejunal AP isoform (IAP) was fractionated by the fast protein-liquid chromatography and purified IAP fractions were kinetically characterized to be the higher-affinity and lower-capacity glycosylated mature IAP (p < 0.05) in comparison with the lower-affinity and higher-capacity non-glycosylated pre-mature IAP. The second approach enzyme activity kinetic analyses showed that N-deglycosylation of AP by the peptide N-glycosidase-F enzyme reduced (p < 0.05) the IAP maximal activity in the jejunum and ileum and decreased AP affinity (p < 0.05) in the large intestine. In the third approach, the porcine IAP isoform-X1 (IAPX1) gene was overexpressed in the prokaryotic ClearColiBL21 (DE3) cell and the recombinant porcine IAPX1 was associated with reduced (p < 0.05) enzyme affinity and maximal enzyme activity. Therefore, levels of glycosylation can modulate plasticity of weaned porcine gut AP functionality towards maintaining gut microbiome and the whole-body physiological status.

Abstract Increased gut permeability facilitates the uptake of food allergens into the bloodstream and triggers allergenic reactions. The present study aimed to evaluate the effect of Lactobacillus pentosus S-PT84 (S-PT84) and Rubus suavissimus leaf extract (RSLE) against egg ovomucoid (OVM)-uptake in lipopolysaccharide (LPS)-induced increased gut-permeability mice model of food allergy. Six-eight weeks old, female C57BL6 mice were continuously fed with LPS (300 μg/kg BW), for 3 months to increase gut permeability. Reduction in the expression of sealing claudin-4, increase in the expression of pore-forming claudin-2, and increase in D-mannitol absorption into the blood plasma in the LPS treated groups suggested the increase in gut permeability after LPS treatment. The oral administration of major egg allergen, OVM, after LPS intervention, significantly increased the plasma mast cell protease-1 and OVM-specific IgE compared to the negative control group. These results indicated that continuous LPS intervention developed OVM-induced food allergy. However, both the treatment of S-PT84 and RSLE suppressed the claudin-2 expression and the gut permeability induced by LPS. Furthermore, S-PT84 and RSLE treatment also reduced the plasma mast cell protease-1 and OVM-specific IgE, indicating the potential beneficial effect against LPS intervention developed OVM-induced food allergy. These findings suggest that S-PT84 and RSLE ameliorated LPS induced gut permeability and food allergic reactions.

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.

The eggshell membrane (ESM), mainly composed of collagen-like proteins, is readily available as a waste product of the egg industry. As a novel biomaterial, ESM is attractive for its applications in the nutraceutical, cosmetic, and pharmaceutical fields. This review provides the main information about the structure and chemical composition of the ESM as well as some approaches for its isolation and solubilization. In addition, the review focuses on the role and performance of bioactive ESM-derived products in various applications, while a detailed literature survey is provided. The evaluation of the safety of ESM is also summarized. Finally, new perspectives regarding the potential of ESM as a novel biomaterial in various engineering fields are discussed. This review provides promising future directions for comprehensive application of ESM.

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

Inflammatory bowel diseases (IBD) comprises of ulcerative colitis (UC) and Cohn’s disease (CD) as two main idiopathic pathologies resulting in immunologically mediated chronic inflammatory conditions. Several bioactive peptides and hydro lysates from natural sources have now been tested in animal models of human diseases for potential anti-inflammatory effects. Eggshell membrane (ESM) is a well-known natural bioactive material. In this study, we aim to study the anti-inflammatory activity of ESM hydro lysate (AL-PS) in vitro and in vivo. In vitro, AL-PS was shown to inhibit pro-inflammatory cytokine IL-8 secretion. In vivo treatment with AL-PS was shown to reduce dextran sodium sulphate (DSS)-induced weight loss, clinical signs of colitis and secretion of interleukin (IL)-6 (p < 0.05). In addition, treatment with AL-PS also attenuated the severity of intestinal inflammation via down-regulation of IL-10 an anti-inflammatory cytokine. This validates potential benefits of AL-PS as a novel preventative target molecule for treatment of IBD.

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.

The purpose of this study was to identify the anti-inflammatory activity and mechanism of isomaltodextrin (IMD) in a C57BL/6NCrl mouse model with lipopolysaccharide (LPS)-induced systemic low-grade chronic inflammation and the effect on inflammation-induced potential risk of metabolic disorders. Pre-treatment of IMD decreased the production of pro-inflammatory mediators, TNF-α and MCP-1, and stimulated the production of the anti-inflammatory mediator, adiponectin by increasing the protein expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) in the white adipose tissues. IMD administration reduced plasma concentrations of endotoxin, decreased macrophage infiltration into adipocytes, and increased expression of mucin 2, mucin 4, and the tight junction protein claudin 4. These results suggest that IMD administration exerted an anti-inflammatory effect on mice with LPS-induced inflammation, potentially by decreasing circulating endotoxin, suppressing pro-inflammatory mediators and macrophage infiltration, or by improving mucus or tight junction integrity. IMD exerted protein expression of insulin receptor subset-1 (IRS-1). IMD alleviated the disturbance of gut microflora in LPS-treated mice, as the number of B. bifidum, L. casei, and B. fragilis increased, and E. coli and C. difficile decreased, when compared to LPS-treated mice. The analysis of short chain fatty acids (SCFAs) further supported that the concentrations of acetic and butyric acids were positively correlated with IMD, as well as the number of beneficial bacteria. This study provides evidence that IMD possesses anti-inflammatory properties and exerts beneficial functions to prevent systemic low-grade chronic inflammation and reduces the risk of developing insulin resistance and associated metabolic diseases.

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.

The objective of the study was to compare the antioxidant activity of two distinct hydrolysates and their peptide fractions prepared by ultrafiltration (UF) using membranes with molecular weight cut-off of 5 and 1 kDa. The hydrolysates were a delipidated egg yolk protein concentrate (EYP) intensively hydrolyzed with a combination of two bacterial proteases, and a phosphoproteins (PPP) extract partially hydrolyzed with trypsin. Antioxidant activity, as determined by the oxygen radical absorbance capacity (ORAC) assay, was low for EYP and PPP hydrolysates with values of 613.1 and 489.2 µM TE×g−1 protein, respectively. UF-fractionation of EYP hydrolysate increased slightly the antioxidant activity in permeate fractions (720.5–867.8 µM TE×g−1 protein). However, ORAC values were increased by more than 3-fold in UF-fractions prepared from PPP hydrolysate, which were enriched in peptides with molecular weight lower than 5 kDa. These UF-fractions were characterized by their lower N/P atomic ratio and higher phosphorus content compared to the same UF-fractions obtained from EYP-TH. They also contained high amounts of His, Met, Leu, and Phe, which are recognized as antioxidant amino acids, but also high content in Lys and Arg which both represent target amino acids of trypsin used for the hydrolysis of PPP.

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.

It is widely recognized that eggs are more than a source of dietary nutrients, and extensive studies identifying and characterizing the biologically active components of eggs have been carried out. Numerous biological activities have now been associated with egg components, including antibacterial and antiviral activity, immunomodulatory activity, and anti-cancer activity, indicating the importance of eggs and egg components in human health, and disease prevention and treatment. The potential of some of these biologically active components has already been realized, including egg white lysozyme and avidin, and yolk IgY and lecithin, which are currently produced on an industrial scale, and have been applied for the prevention and treatment of various medical conditions. The information presented here serves to demonstrate the significant potential of biologically active egg components, for medical, nutraceutical, and food-fortification applications.