Heat-killed cells of lactobacilli skew the immune response toward T helper 1 polarization in mouse splenocytes and dendritic cell-treated T cells

It is believed that probiotics play an important role for the health of the host, including modulation of immune responses. Most studies have focused on the immunomodulatory effects of viable cells of lactic acid bacteria; however, we investigated those of heat-killed cells of lactic acid bacteria in this study. We first observed the effects on immune functions via stimulating splenocytes with three heat-killed Lactobacillus strains. Furthermore, we also investigated the effect of mouse dendritic cells (DCs) treated with these heat-killed Lactobacillus strains on T cell responses. The results showed that these Lactobacillus strains were able to stimulate cell proliferation and interleukin (IL)-10, IL-12 p70, and interferon (IFN)-gamma production but not transforming growth factor (TGF)-beta in splenocytes. In addition, these heat-killed Lactobacillus strains also stimulated high-level secretion of IL-12 p70 in DCs and switched T cells to T helper (Th) 1 immune responses, as evidenced by the elevated secretion of IFN-gamma but not IL-5, IL-13, and TGF-beta. These results showed that lactobacilli play a potentially important role in modulating immune responses and allergic reactions.     

C-phycocyanin, a very potent and novel platelet aggregation inhibitor from Spirulina platensis

The aim of this study was to systematically examine the inhibitory mechanisms of C-phycocyanin (C-PC), one of the major phycobiliproteins of Spirulina platensis (a blue-green alga), in platelet activation. In this study, C-PC concentration-dependently (0.5-10 nM) inhibited platelet aggregation stimulated by agonists. C-PC (4 and 8 nM) inhibited intracellular Ca2+ mobilization and thromboxane A2 formation but not phosphoinositide breakdown stimulated by collagen (1 microg/mL) in human platelets. In addition, C-PC (4 and 8 nM) markedly increased levels of cyclic GMP and cyclic GMP-induced vasodilator-stimulated phosphoprotein (VASP) Ser(157) phosphorylation. Rapid phosphorylation of a platelet protein of Mw 47,000 (P47), a marker of protein kinase C activation, was triggered by phorbol-12,13-dibutyrate (150 nM). This phosphorylation was markedly inhibited by C-PC (4 and 8 nM). In addition, C-PC (4 and 8 nM) markedly reduced the electron spin resonance (ESR) signal intensity of hydroxyl radicals in collagen (1 microg/mL)-activated platelets. The present study reports on a novel and very potent (in nanomolar concentrations) antiplatelet agent, C-PC, which is involved in the following inhibitory pathways: (1) C-phycocyanin increases cyclic GMP/VASP Ser157 phosphorylation and subsequently inhibits protein kinase C activity, resulting in inhibition of both P47 phosphorylation and intracellular Ca2+ mobilization, and (2) C-PC may inhibit free radicals (such as hydroxyl radicals) released from activated platelets, which ultimately inhibits platelet aggregation. These results strongly indicate that C-PC appears to represent a novel and potential antiplatelet agent for treatment of arterial thromboembolism.     

Immunomodulatory effects of heated ovomucoid-depleted egg white in a BALB/c mouse model of egg allergy

Oral immunotherapy (OIT) is a promising therapeutic approach for treating food allergy. The treatment with heated ovomucoid-depleted egg white (HOMEW) in egg-allergic patients is noteworthy; however, OIT protocols are still experimental, and a better knowledge of the underlying mechanism is required. The objective of this work was to investigate the immunomodulatory effects of HOMEW and characterize the underlying mechanism in a BALB/c mouse model of egg allergy. Mice were sensitized with EW and treated with HOMEW. Post treatment, mice were challenged with EW and euthanized for collecting blood and spleen. Markers of allergic clinical outcomes were measured as histamine concentration, serum antibody activity, and cytokine production from cultured splenocytes. Digestibility of HOMEW was assessed mimicking physiological conditions in vitro. The HOMEW demonstrated high digestibility. The treatment induced a marked increase of the Th1/Th2 ratio in the high-dose treatment group. Treated mice had significantly less histamine, EW-specific IgE, and IL-4 and more IFN-γ and IL-10. This study confirms the mechanisms involved in successful tolerance induction with OIT using HOMEW and allows understanding of the vital role of surrogate allergy markers involved in immune modulation.     

Modulation of cytokine secretion by garlic oil derivatives is associated with suppressed nitric oxide production in stimulated macrophages

We previously described that garlic oil derivatives differentially suppress the production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) in activated macrophages. In the present study, we investigated the effects of the garlic derivatives, diallyl sulfide (DAS), diallyl disulfide (DADS), and allyl methyl sulfide (AMS), on cytokine production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, and the association between modulation of cytokines and inhibition of NO production was also assessed. The results indicated that these garlic compounds had different effects on the secretion of activated cytokines, including proinflammatory tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6, as well as the antiinflammatory, IL-10. DAS inhibited the production of all stimulated cytokines in a concentration-dependent manner, and the inhibition was closely associated with the suppression of NO and PGE(2) production. DADS repressed the production of stimulated TNF-alpha and IL-10 and increased the production of activated IL-1beta and, to a lesser extent, IL-6; but only the decreased IL-10 production was associated with DADS-induced NO inhibition. Yet, the DAS- and DADS-suppressed NO production was independent of TNF-alpha. AMS, on the other hand, slightly suppressed the stimulated TNF-alpha but enhanced IL-10 production, and such modulation was closely associated with the decrease in NO production.     

Antiinflammatory flavonoids from Artocarpus heterophyllus and Artocarpus communis

The antiinflammatory activities of the isolated flavonoids, including cycloartomunin (1), cyclomorusin (2), dihydrocycloartomunin (3), dihydroisocycloartomunin (4), cudraflavone A (5), cyclocommunin (6), and artomunoxanthone (7), and cycloheterohyllin (8), artonins A (9) and B (10), artocarpanone (11), artocarpanone A (12), and heteroflavanones A (13), B (14), and C (15) from Artocarpus communis and A. heterophyllus, were assessed in vitro by determining their inhibitory effects on the chemical mediators released from mast cells, neutrophils, and macrophages. Compound 4 significantly inhibited the release of beta-glucuronidase and histamine from rat peritoneal mast cells stimulated with P-methoxy-N-methylphenethylamine (compound 48/80). Compound 11 significantly inhibited the release of lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP). Compounds 8, 10, and 11 significantly inhibited superoxide anion formation in fMLP-stimulated rat neutrophils while compounds 2, 3, 5, and 6 evoked the stimulation of superoxide anion generation. Compound 11 exhibited significant inhibitory effect on NO production and iNOS protein expression in RAW 264.7 cells. The potent inhibitory effect of compound 11 on NO production in lipopolysaccharide (LPS)-activated macrophages, probably through the suppression of iNOS protein expression.     

Suppression of allergic reactions by dehulled adlay in association with the balance of TH1/TH2 cell responses

Dehulled adlay is known as a natural Chinese medicine having antiallergic activity, although its mechanism remains unclear. This study examined the effects of dehulled adlay on antigen-specific antibody and cytokine production. Mice were immunized three times with ovalbumin (OVA) in alum adjuvant. It was found that oral administration of dehulled adlay in mice suppressed the production of IgE against OVA antigen. Serum anti-OVA IgG(2a) antibody levels were significantly increased in mice after oral administration of dehulled adlay. Furthermore, the production of IL-2 by OVA-stimulated splenocytes was augmented in dehulled adlay-fed mice. Although dehulled adlay had no effect on the serum anti-OVA IgG(1) antibody levels, it had a great capacity to reduce IL-5 secretion by means of OVA-stimulated splenocytes. Hydrothermal processes, including steaming and extrusion cooking, did not change the capacity of dehulled adlay to suppress IgE production. Three fractions of dehulled alday, including methanolic extract, warm water extract, and residue, were obtained. The methanolic extract exhibited the greatest capacity to reduce anti-OVA IgE production. These results suggest that dehulled adlay has a modulating ability to shift the balance from Th2 to Th1 dominance in the T cell mediated immune system and may be beneficial for the treatment of allergic disorders.     

In vivo anti-influenza virus activity of an immunomodulatory acidic polysaccharide isolated from Cordyceps militaris grown on germinated soybeans

An acidic polysaccharide (APS) was isolated from the extract of Cordyceps militaris grown on germinated soybeans. Analyses of sugar composition indicated that APS consisted of d-galactose, L-arabinose, D-xylose, L-rhamnose, and D-galacturonic acid. On the basis of the result of methylation analysis, APS was considered to be mainly composed of Araf-(1-->, -->5)-Araf-(1-->, -->4)-Galp-(1--> and -->4)-GalAp-(1--> residues. When the polysaccharide was intranasally administered, it decreased virus titers in the bronchoalveolar lavage fluid and the lung of mice infected with influenza A virus and increased survival rate. Furthermore, APS increased TNF-alpha and IFN-gamma levels in mice when compared with those of untreated mice. APS enhanced nitric oxide (NO) production and induced iNOS mRNA and protein expressions in RAW 264.7 murine macrophage cells. The induction of mRNA expression of cytokines including IL-1beta, IL-6, IL-10, and TNF-alpha was also observed. These results demonstrated that APS might have beneficial therapeutic effects on influenza A virus infection at least in part by modulation of the immune function of macrophages.     

Effect of yak milk casein hydrolysate on TH1/TH2 cytokines production by murine spleen lymphocytes in vitro

Yak casein hydrolysate was derived from the enzymatic alcalase-hydrolysate of a typical northwestern China milk product called Qula. An in vitro study was conducted to examine their immunoregulatory effects on murine T cells, including Con-A-induced lymphoproliferation and splenocyte cell cycle, production, and messenger RNA (mRNA) expression of interleukin-2 (IL-2), interferon-gamma (IFN-gamma), and interleukin-4 (IL-4). The results showed that yak casein hydrolysate had lymphoproliferation activity on murine splenocytes and induced their cell cycle from the G1 to the S phase. It could increase Con-A-induced IL-2 and IFN-gamma production in spleen cells, but a very weak or no effect was observed in the absence of Con-A. The present study also showed that it could markedly increase the production and mRNA expression of IFN-gamma and IL-2, which are key cytokines for T helper 1 cell (Th1) cell development, in a dose-dependent manner. However, their effects on IL-4 secretion were not obvious, and the enhancement was much lower than that of IFN-gamma and IL-2. All of these demonstrated that yak casein hydrolysate could increase type 1 cytokine production, thereby shifting the Th1/T helper 2 cell (Th2) balance toward a Th1-dominant phenotype, which meant that yak casein hydrolysate could indeed not only modulate the differentiation of helper T cell but also has the capacity to modulate the Th1/Th2 balance. Therefore, yak casein hydrolysate may be useful for the treatment of cell-mediated immune diseases.     

Antiallergic effect of milk fermented with lactic acid bacteria in a murine animal model

The objective of this study was to assess the antiallergic effect of fermented milk prepared, respectively, with Streptococcus thermophilus MC, Lactobacillus acidophilus B, Lactobacillus bulgaricus Lb, L. bulgaricus 448, and Bifidobacterium longum B6. Female BALB/c mice fed fermented milk were immunized intraperitoneally with ovalbumin (OVA)/complete Freund's adjuvant (CFA) to evaluate the immune response by observing the secretion of cytokines IL-2, IL-4, and IFN-gamma and serum antibody IgE. The results showed that supplementation with lactic acid bacteria fermented milk did not significantly change the IL-2 spontaneous and OVA-stimulated secretions of splenocytes. However, both spontaneous and OVA-stimulated secretions of splenocytes from mice fed lactic acid bacteria fermented milk showed significantly (P < 0.05) lower levels of IL-4 (Th2 cytokine) than those from OVA/CFA-immunized mice fed non-fermented milk (OVA/CFA-milk group). The spontaneous secretion of IFN-gamma (Th1 cytokine) by splenocytes from mice fed L. bulgaricus 448 or L. bulgaricus Lb fermented milk significantly increased as compared to that from the OVA/CFA-milk group. The results showed that the ratios of IFN-gamma to IL-4 of both spontaneous and OVA-stimulated secretions in splenocytes from mice fed lactic acid bacteria fermented milk increased significantly as compared to that of PBS- or OVA/CFA-milk groups. The serum levels of OVA-specific IgE in fermented milk fed groups, especially the group fed S. thermophilus MC fermented milk, were significantly lower than those in the OVA/CFA-milk group through a 6 week feeding experiment. The results showed that milk fermented with lactic acid bacteria demonstrated in vivo antiallergic effects on OVA/CFA-immunized mice via increasing the secretion ratio of IFN-gamma/IL-4 (Th1/Th2) by splenocytes and decreasing the serum level of OVA-specific IgE.     

Specific immunomodulatory and secretory activities of stevioside and steviol in intestinal cells

Stevioside, isolated from Stevia rebaudiana, is a commercial sweetener. It was previously demonstrated that stevioside attenuates NF-kappaB-dependent TNF-alpha and IL-1beta synthesis in LPS-stimulated monocytes. The present study examined the effects of stevioside and its metabolite, steviol, on human colon carcinoma cell lines. High concentrations of stevioside (2-5 mM) and steviol (0.2-0.8 mM) decreased cell viability in T84, Caco-2, and HT29 cells. Stevioside (2 mM) potentiated TNF-alpha-mediated IL-8 release in T84 cells. However, steviol (0.01-0.2 mM) significantly suppressed TNF-alpha-induced IL-8 release in all three cell lines. In T84 cells, steviol attenuated TNF-alpha-stimulated IkappaB --> NF-kappaB signaling. Chloride transport was stimulated by steviol (0.1 mM) > stevioside (1 mM) at 30 min. Two biological effects of steviol in the colon are demonstrated for the first time: stimulation of Cl(-) secretion and attenuation of TNF-alpha-stimulated IL-8 production. The immunomodulatory effects of steviol appear to involve NF-kappaB signaling. In contrast, at nontoxic concentrations stevioside affects only Cl(-) secretion.     

Sialic acid-containing milk proteins show differential immunomodulatory activities independent of sialic acid

The immunomodulatory activities of four sialic acid-containing milk proteins (kappa-casein, glycomacropeptide, lactoferrin, and proteose peptone-3 component) were determined, and the role of sialic acid was evaluated. Two in vitro models were used: murine splenocyte proliferation, where the effect on LPS-, Con A-, and PHA-stimulated proliferation was studied, and cytokine production in LPS-stimulated murine dendritic cells (DC). All four proteins inhibited LPS-induced splenocyte proliferation, though to different degrees, and independently of sialic acid. kappa-Casein strongly inhibited PHA-induced proliferation and had a weak inhibitory effect on Con A-induced proliferation, whereas lactoferrin stimulated Con A-induced proliferation. kappa-Casein, glycomacropeptide, and lactoferrin differentially affected cytokine production by DC: kappa-casein significantly inhibited production of TNF-alpha, IL-10, -12, -6, and -1beta, independent of sialic acid, whereas less-marked effects of glycomacropeptide and lactoferrin were seen. These findings thus point to important immunosuppressive effects of some milk proteins and indicate that they may function via different mechanisms.     

Fungal immunomodulatory protein from Flammulina velutipes induces interferon-gamma production through p38 mitogen-activated protein kinase signaling pathway

FIP-fve is a fungal immunomodulatory protein purified from Flammulina velutipes, an edible golden needle mushroom thought to possess potent immunomodulatory properties. When examined for its effects on lymphocytes, FIP-fve exhibited potent mitogenic effects on human peripheral blood lymphocytes, inducing G1/G0 to S phase proliferation. T cells activated by FIP-fve show significant production and secretion of interferon-gamma (IFN-gamma) associated with intercellular adhesion molecule 1 expression but low detectable levels of interleukin-4 in vitro or in vivo. However, SB203580, the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor, can fully abolish the production of IFN-gamma induced by FIP-fve. At the same time, SB203580 only partially prevents the lymphocytes from progressing from G1 to S phase of the cell cycle. These findings demonstrate that FIP-fve is a potent T-cell activator, mediating its effects via cytokine regulation of p38 MAPK. The immunoprophylatic effects of FIP-fve in Th2-mediated allergic anaphylaxis are believed to be associated with the ability of FIP-fve to enhance activation of IFN-gamma-releasing Th1 cells.     

Physiological difference between free and triglyceride-type conjugated linoleic acid on the immune function of C57BL/6N mice

Previous studies have shown the physiological significance of dietary conjugated linoleic acid (CLA) in various experimental animals and in human beings. One of the important problems to better elucidate is the difference between triglyceride (TG) and free (FFA) dietary CLA. Here, using splenocytes, this study assesses how TG- and FFA-CLA modulate immunoglobulin and various cytokine productions. In this study, C57BL/6N mice were fed an experimental diet containing 0% CLA, 0.1 or 1% FFA-CLA, or 0.1 or 1% TG-CLA for 3 weeks. The production of immunoglobulin tended to be up-regulated by 1% FFA-CLA. As a result of protein array analysis using the supernatant from splenocytes cultured with no CLA, 1% FFA-CLA, and TG-CLA, some cytokine production was shown to be remarkably regulated by dietary FFA- and TG-CLA. A total of 32 cytokines were examined, and 11-14 produced cytokines that were 2-fold up-regulated as compared with control for FFA- or TG-CLA, respectively. Especially, the production of IL-9 and MCP-5 and other cytokines was remarkably up-regulated by both FFA- and TG-CLA. In addition, seven cytokines were 2-fold down-regulated by TG-CLA. These data show that there is a slight but significant difference between the functionalities of FFA- and TG-CLA.     

Effects of water-soluble hemicellulose from soybean hull on serum antibody levels and activation of macrophages in rats

Effects of soybean hull water-soluble hemicellulose (WSHC) on serum immunoglobulin (Ig) concentration and production of NO and IL-1beta from peritoneal macrophages were examined and compared with those of Agaricus blazei in the rat system. WSHC consisted of arabinose, galactose, xylose, glucose, and rhamnose, and the molecular weight was approximately 500000. Rats were ip administrated each sample at a dose of 0.67, 13.4, or 26.9 mg/kg/day for 14 days. The administration of WSHC resulted in significantly higher productions of IgM (p < 0.01 on day 6, p < 0.05 on day 14) and IgG (p < 0.05 on day 6) than those in other groups. When peritoneal macrophages were stimulated with various concentrations of sample (0.67, 13.4, or 26.9 mg/mL), WSHC significantly increased both NO and IL-1beta productions only at the concentration of 13.4 (mg/mL) compared with those of a saline group. These findings demonstrate that WSHC enhances humoral immunity and activation of macrophages, thereby leading to the augmentation of immune responses in rats.     

Inhibitory effect of (-)-epigallocatechin 3-gallate, a polyphenol of green tea, on neutrophil chemotaxis in vitro and in vivo

The effect of (-)-epigallocatechin 3-gallate (EGCG), a major polyphenol of green tea, on neutrophil migration has been studied using multiwell-type Boyden chambers in vitro and a fluorescein isothiocyanate-labeled ovalbumin (FITC-OVA)-induced rat allergic inflammation model in vivo. EGCG inhibited rat neutrophil chemotaxis toward cytokine-induced neutrophil chemoattractant-1 (CINC-1) in a concentration-dependent manner. In addition, CINC-1-induced neutrophil chemotaxis was suppressed by the pretreatment of rat neutrophils with EGCG at the concentration over 15 microg/mL. EGCG caused concentration-dependent suppression of the transient increase in CINC-1-induced intracellular free calcium level in both rat neutrophils and rat CXC chemokine receptor 2 (CXCR2)-transfected HEK 293 cells. EGCG inhibited CINC-1 production by IL-1beta-stimulated rat fibroblasts (NRK-49F cells) and lipopolysaccharide-stimulated rat macrophages at the concentration over 50 microg/mL, a comparatively high concentration. Oral administration of EGCG (1.0 mg or 1.5 mg/rat) at 1 h before the challenge with FITC-OVA suppressed neutrophil infiltration into the air pouch (inflammatory site) in the air-pouch type FITC-OVA-induced allergic inflammation in rats. Chemokine levels in the pouch fluids, however, were not influenced by EGCG administration. The results suggest that EGCG suppressed neutrophil infiltration by a direct action on neutrophils, but not by indirect actions, including the suppression of chemokine production at the inflammatory site.     

Grape-seed procyanidins act as antiinflammatory agents in endotoxin-stimulated RAW 264.7 macrophages by inhibiting NFkB signaling pathway

Procyanindin extract (PE) is a mixture of polyphenols, mainly procyanidins, obtained from grape seed with putative antiinflammatory activity. We evaluated the PE effect on RAW 264.7 macrophages stimulated with lipopolysaccharide plus interferon-gamma that show a rapid enhanced production of prostaglandin E2 (PGE2) and nitric oxide (NO). Our results demonstrated that PE significantly inhibited the overproduction of NO, dose and time dependently. PE caused a marked inhibition of PGE2 synthesis when administered during activation. Moreover, PE pretreatment diminished iNOS mRNA and protein amount dose dependently (10-65 microg/mL). PE (65 microg/mL) pretreatment inhibited NFkappaB (p65) translocation to nucleus by nearly 40%. Trimeric and longer oligomeric-rich procyanidin fractions from PE (5-30 microg/mL) inhibited iNOS expression but not the monomeric forms catechin and epicatechin. Thus, we show that the degree of polymerization is important in determining procyanidin effects. PE was considerably a more effective inhibitor of NO biosynthesis (IC50 = 50 microg/mL) in comparison to other antiinflammatories, such as aspirin (3 mM), indomethacin (20 microM), and dexamethasone (9 nM). In conclusion, PE modulates inflammatory response in activated macrophages by the inhibition of NO and PGE2 production, suppression of iNOS expression, and NFkB translocation. These results demonstrate an immunomodulatory role of grape seed procyanidins and thus a potential health-benefit in inflammatory conditions that exert an overproduction of NO and PGE2.     

Anti-inflammatory activities of new succinic and maleic derivatives from the fruiting body of Antrodia camphorata

Six new compounds, trans-3-isobutyl-4-[4-(3-methyl-2-butenyloxy)phenyl]pyrrolidine-2,5-dione (1), trans-1-hydroxy-3-(4-hydroxyphenyl)-4-isobutylpyrrolidine-2,5-dione (2), cis-3-(4-hydroxyphenyl)-4-isobutyldihydrofuran-2,5-dione (3), 3-(4-hydroxyphenyl)-4-isobutyl-1H-pyrrole-2,5-dione (4), 3-(4-hydroxyphenyl)-4-isobutylfuran-2,5-dione (5), and dimethyl 2-(4-hydroxyphenyl)-3-isobutylmaleate (6), together with one known compound, 3-isobutyl-4-[4-(3-methyl-2-butenyloxy)phenyl]furan-2,5-dione (7), were isolated from the fruiting bodies of Antrodia camphorata. The structures of the compounds were elucidated by analysis of their spectroscopic data. To investigate the immunomodulatory potential of the compounds, RAW264.7 macrophage cells were treated with the compounds. Compound 1 significantly increased spontaneous TNF-alpha secretion from unstimulated RAW264.7 cells but suppressed IL-6 production [50% inhibition concentration value (IC50) = 10 microg/mL] in LPS-stimulated cells. Compounds 3, 4, and 6 also suppressed IL-6 production with IC50 values of 17, 18, and 25 microg/mL, respectively, suggesting that these four compounds may have an anti-inflammatory effect on macrophage-mediated responses. Of the six compounds, compound 1 was the most effective, exerting both immunostimulatory and anti-inflammatory effects.     

Phenolic acids are in vivo atheroprotective compounds appearing in the serum of rats after blueberry consumption

Blueberries (BB) have recently been shown to have cardioprotective effects and to prevent atherosclerosis in rodent models. However, the bioactive compounds in BB responsible for these effects have not yet been characterized. Seven phenolic acids (7PA) were identified as metabolites in the serum of rats fed diets supplemented with 10% freeze-dried BB. In this study, 7PA were evaluated for their potential atheroprotective effects in murine macrophage cell line RAW 264.7. 7PA were found to inhibit LPS-induced mRNA expression and protein levels of pro-inflammatory cytokine TNF-α and IL-6 by reducing MAPK JNK, p38, and Erk1/2 phosphorylation. After treatment with 7PA for 2 weeks, mRNA expression and protein levels of scavenger receptor CD36 were decreased (P<0.05), whereas type A scavenger receptor (SR-A) remained unchanged. Moreover, foam cell formation induced by oxLDL and oxLDL binding to macrophages was also inhibited by 7PA. In addition, 7PA increased (P<0.05) expression and protein levels of ATP-binding cassette transporter A1 (ABCA1), which facilitates cholesterol efflux and reduces cholesterol accumulation in macrophages. In summary, the present study demonstrates that certain phenolic acids are potential in vivo atheroprotective compounds following BB consumption in the rodent model. Because BB contain many phytochemicals, other as yet unidentified bioactive compounds may also be important in preventing atherosclerosis in this model and, possibly, in humans.     

Effect of heat-inactivated kefir-isolated Lactobacillus kefiranofaciens M1 on preventing an allergic airway response in mice

In this study, we assessed the anti-asthmatic effects of heat-inactivated Lactobacillus kefiranofaciens M1 (HI-M1) and its fermented milk using different feeding procedures and at various dosage levels. The possible mechanisms whereby HI-M1 has anti-allergic asthmatic effects were also evaluated. Ovalbumin (OVA)-allergic asthma mice that have been orally administrated the HI-M1 samples showed strong inhibition of production of T helper cell (Th) 2 cytokines, pro-inflammatory cytokines, and Th17 cytokines in splenocytes and bronchoalveolar fluid compared to control mice. An increase in regulatory T cell population in splenocytes in the allergic asthma mice after oral administration of H1-M1 was also observed. In addition, all of the features of the asthmatic phenotype, including specific IgE production, airway inflammation, and development of airway hyperresponsiveness, were depressed in a dose-dependent manner by treatment. These findings support the possibility that oral feeding of H1-M1 may be an effective way of alleviating asthmatic symptoms in humans.