OVA-induced Allergic Rhinitis Research Articles

Anti-allergic effect of a Korean traditional medicine, Biyeom-Tang on mast cells and allergic rhinitis

BackgroundBiyeom-Tang, a medicine prescribed by oriental clinics, has been used for the treatment of the allergic rhinitis (AR). In the present study, an ethanol extract of Biyeom-Tang (EBT) was investigated for anti-allergic properties on bone-marrow derived mast cells (BMMC) and in vivo models.MethodsThe anti-allergic properties of EBT were evaluated by measuring β-Hex release and the production of prostaglandin D2 (PGD2) and leukotriene C4 (LTC4) on BMMC in vitro and PCA and OVA-induced AR models in vivo.ResultsEBT strongly inhibited a degranulation reaction in a dose dependent manner with an IC50 value of 35.6 μg/ml. In addition, the generation of PGD2 and LTC4 was inhibited in BMMC in a concentration-dependent manner with IC50 values of 7.0 μg/ml and 10.9 μg/ml, respectively. When administrated orally, EBT ameliorated the mast cell-mediated PCA reaction. In the OVA-induced AR model, the increased levels of IgE were reduced by EBT. The levels of cytokines, such as IL-4, IL-5, IL-10, and IL-13 decreased in the splenocytes of EBT-treated mice. The histological analysis shows that the infiltration of inflammatory cells increased by OVA-sensitization was also reduced.ConclusionsTaken together, these results suggested that EBT has anti-allergic and anti-inflammatory effects in vitro and in vivo models.

The (2′S,7′S)-O-(2-methylbutanoyl)-columbianetin as a novel allergic rhinitis-control agent

AimsThe (2′S,7′S)-O-(2-methylbutanoyl)-columbianetin (OMC) is a novel secondary metabolite extracted from Corydalis heterocarpa, which has long been used as a folk medicine for various inflammatory diseases in Korea. We examined the effect of OMC on allergic rhinitis (AR). Main methodsWe assessed the therapeutic effects and regulatory mechanisms of OMC on the phorbol 12-myristate 13-acetate plus A23187-stimulated mast cell line, HMC-1 cells and ovalbumin (OVA)-induced AR models. Key findingsOMC significantly decreased the releases of histamine and tryptase from stimulated HMC-1 cells. The degranulation process, characterized by morphological extension of the filopodia on the surface and membrane ruffling, was strongly induced in the stimulated-HMC-1 cell, however OMC suppressed the morphological changes in stimulated-HMC-1 cells. OMC reduced the production and mRNA expression of inflammatory cytokines. These inhibitory actions by OMC were dependent on the regulation of mitogen-activated protein kinases, nuclear factor-κB, and caspapase-1 signaling pathways. In the AR animal model, the increased rub scores and AR biomarkers (histamine and IgE) in ovalbumin (OVA)-sensitized mice were significantly reduced by the administration of OMC. Furthermore, eosinophils and mast cell infiltrations in nasal mucosa tissue were also blocked through the regulation of macrophage-inflammatory protein and intercellular adhesion molecule-1 levels. SignificanceOMC showed the possibility to regulate AR in activated mast cells and OVA-induced AR models. Hence, we suggest that OMC is a powerful and feasible new agent to suppress AR.

Plant homeodomain finger protein 11 promotes class switch recombination to IgE in murine activated B cells

Polymorphisms of the Plant homeodomain finger protein 11 (PHF11) are strongly associated with high serum IgE levels and clinical severity of atopic patients. However, the precise mechanism has not been fully elucidated. We investigated the role of Phf11 in class switch recombination (CSR) to IgE by activated B cells. We generated Phf11 transgenic (Lckd-Phf11-Tg) mice that express the exogenous murine Phf11 in lymphocytes under the control of distal Lck promoter. We examined IL-4-induced CSR to IgE in activated Lckd-Phf11-Tg B cells in vitro. We analyzed production of ovalbumin (OVA)-specific IgE and nose-scratching symptoms in Lckd-Phf11-Tg mice using an OVA-induced allergic rhinitis model. The exogenous Phf11 promoted CSR to IgG1 and IgE in activated B cells with an increase in germ line transcript (GLT) γ1 and GLT ε expression. The exogenous Phf11 augmented transcriptional activity of the GLT γ1 and GLT ε promoters through permissive histone modifications and binding of NF-κB and STAT6. Furthermore, the exogenous Phf11 bound to the GLT ε promoter with increased binding of NF-κB. Silencing of the endogenous Phf11 reduced the frequency of CSR to IgE and GLT ε expression, but not to IgG1 or GLT γ1 expression, in activated B cells. In an allergic rhinitis model, Lckd-Phf11-Tg mice showed a significant increase in the production of OVA-specific IgE and the frequency of nose scratching. Phf11 accelerates CSR to IgE in activated B cells by increasing the transcriptional activity of GLT ε promoter and contributes to the exacerbation of allergic responses. These findings provide a novel therapeutic target for allergic diseases.

방풍(防風)의 난알부민 유도 알레르기 비염 마우스에서의 항알레르기 효능 연구

Objectives : In this study, we investigated the effect of Saposhnikoviae Radix on allergic responses in ovalbumin(OVA)-induced Allergic rhinitis(AR) mice. Methods : BALB/c mice were orally administrated with Saposhnikoviae Radix water extract (SRW, 50 mg/kg) or anti-histamine drug, Ketotifen (10 mg/kg) as a reference drug, followed by sensitization and challenge of OVA. Mice were measured clinical symptoms and the serum levels of histamine, IgE, IL-4, and IFN-<TEX>${\gamma}$</TEX>, and observed histopathological changes of nasal mucosa H&E staining. Results : SRW significantly decreased rubs and the serum levels of histamine, IgE, and IL-4, and then increased the serum levels of IFN-<TEX>${\gamma}$</TEX> in OVA-induced AR mice, and inhibited histopathological changes of nasal mucosa with inflammation and the eosinophils infilteration. Conclusions : These data suggest that SRW has anti-allergic effect through the inhibitory property of Saposhnikoviae Radix against allergic responses in allergic rhinitis.

알레르기 비염 한약제제 KOB와 주요 구성약물인 황기(黃芪)의 난알부민 유도 알레르기 비염 마우스에서의 항알레르기 효능 연구

Objectives : In this study, we investigated the effect of KOB, a polyherbal medicine for allergic rhinitis and its main herb, Astragali Radix on allergic responses in ovalbumin (OVA)-induced Allergic rhinitis(AR) mice. Methods : Sprague Dawley (SD)-rats were orally administrated with KOB (500 mg/kg), Astragali Radix water extract (ARW, 100 mg/kg) or anti-histamine drug, dosodium cromoglycate (50 mg/kg) as a reference drug, and then intraperitoneally injected with compound 48/80 (8 mg/kg). Rats were measured the mortality and serum levels of histamine. BALB/c mice were orally administrated with KOB (500 mg/kg), ARW (100 mg/kg) or anti-histamine drug, Ketotifen (10 mg/kg) as a reference drug, followed by sensitization and challenge of OVA. Mice were measured the serum levels of histamine and IgE, and observed histopathological changes of nasa mucosa H&E staining. Results : KOB and ARW significantly decreased the mortality and the serum levels of histamine in compound 48/80-induced anaphylatic rats. KOB and ARW also decreased the serum levels of histamine and IgE in OVA-induced AR mice, and inhibited histopathological changes of nasal mucosa with inflammation and the eosinophils infilteration. Conclusions : These data suggest that KOB has a strong anti-allergic effect through the inhibitory property of Astragali Radix, the main component of KOB against allergic responses in allergic rhinitis.

Bamboo salt reduces allergic responses by modulating the caspase-1 activation in an OVA-induced allergic rhinitis mouse model

Bamboo salt (BS) is a specially processed salt according to the traditional recipe using sun-dried salt (SDS) and bamboo in Korea. The present study investigated the effects and mechanism of BS, SDS, NaCl, or mineral mixture (containing zinc, magnesium, and potassium) on ovalbumin (OVA)-induced allergic rhinitis (AR) animal model. The increased number of rubs was inhibited by the oral administration of BS, SDS, NaCl, mineral mixture, or nose inhalation of BS. The increased levels of IgE, histamine, and interleukin (IL)-1β in serum were reduced by BS. The level of interferon-γ was increased, whereas the level of IL-4 was reduced on the spleen tissue of BS-treated mice. In the BS-treated mice, the number of eosinophils and mast cells infiltration increased by OVA-sensitization were also decreased. Protein levels of inflammatory cytokines were reduced by BS or NaCl administration in the nasal mucosa of the AR mice. In addition, BS inhibited caspase-1 activity in the nasal mucosa tissue. In activated human mast cells, BS significantly inhibited the production of IL-1β and thymic stromal lymphopoietin and activation of caspase-1. Our data indicate that BS has anti-allergic and anti-inflammatory effects by regulating of caspase-1 activation in AR mice and in vitro models.

Antiallergic effect of KOB03, a polyherbal medicine, on mast cell-mediated allergic responses in ovalbumin-induced allergic rhinitis mouse and human mast cells

Ethnopharmacological relevanceKOB03 is a polyherbal medicine consisting of five different herbs and has commonly been used for the treatment of various allergic diseases. However, its precise anti-allergic effect and mechanism remain unknown. Aim of the studyThe aim of this study was to investigate the effect of KOB03 on allergic responses through the regulation of mast-cell mediated allergic inflammation. Materials and methodsTo determine the effect of KOB03 on mast cell-mediated allergic reactions, we investigated the parameter changes of in vivo models such as compound 48/80-induced systemic anaphylaxis and ovalbumin (OVA)-induced allergic rhinitis, and the release of allergic inflammatory mediators such as histamine, immunoglobulin (Ig) E, and inflammatory cytokines via the MAPKs and NF-kappaB pathways. ResultsThe oral administration of KOB03 at doses of 100 and 200mg/kg inhibited histamine release and mortality in compound 48/80-induced anaphylactic rats. KOB03 also improved rhinitis symptoms, inhibited the histopathological changes of nasal mucosa, and decreased the serum levels of histamine, OVA-specific IgE and TNF-α in OVA-induced allergic rhinitis in mice. In vitro, KOB03 suppressed compound 48/80-induced histamine release by blocking mast cell degranulation. In addition, KOB03 inhibited the production of inflammatory cytokines such as TNF-α, IL-1β, IL-6 and IL-8 in PMA/A23187-stimulated HMC-1 mast cells by suppressing their gene expression and blocking the ERK1/2 and p38 MAPK and NF-κB pathways. ConclusionsThese results suggest that KOB03 has an anti-allergic effect by modulating mast cell-mediated allergic responses in allergic rhinitis.

Effects of point application on celiac mast cell degranulation in mice with allergic rhinitis: An experimental study

To investigate effects of different treatment on celiac mast cell degranulation in mice with allergic rhinitis induced with ovum albumin (OVA). 60 female mice were randomly divided into five groups, 12 mice in each, which were treated with different methods. Then, the celiac mast cells were separated and degranulation rate was calculated after stained with neutral red. the rates of mast cell degranulation were (15±6)%, (53±11)%, (37±13)%, (31±15)%, and (47±14)% in normal group, OVA group, point application group, hormone group, and PBS group. There is obvious degranulation in the celiac mast cells of mice with OVA-induced allergic rhinitis. Point application and dexamethasone treatment could relieve the mast cell degranulation, whereas, PBS has no effect on the mast cell degranulation. the mechanism of antianaphylaxis of point application may lie on stabilizing the mast cell membrane, and inhibiting degranulation to reduce the inflammatory mediator.

Anti-allergic effect of Osterici Radix water extract in human mast cells

Objectives : Allergy is an immune dysfunction caused by degranulation from mast cells in the early phase of allergic disease including allergic rhinitis (AR). The purpose of this study was to investigate the effects of Osterici Radix, roots of Ostericum koreanum Maximowicz in human mast cells and experimental allergic animal models. Methods : The anti-allergic effect of Osterici Radix water extract (NK-W) was investigated in human mast cell line, HMC-1 cells, and compound 48/80-induced systemic anaphylactic response in rats and ovalbumin (OVA)-induced AR in mice. Animals were orally administrated with NK-W (10 and 50 mg/kg) or anti-histamine drug, dosodium cromoglycate (50 mg/kg), and then intraperitoneally injected with compound 48/80 (8 mg/kg) or sensitized with 0.1% OVA into nasal. Animals were observed plasma histamine and histological changes of nasal mucosa. Also, mast cell degranulation and histamine production were determined in compound 48/80-stimulated HMC-1 cells. Results : NK-W inhibited compound 48/80-induced degranulation of mast cells and histamine releasing in HMC-1 cells. NK-W decreased mortality and serum histamine releasing in compound 48/80-induced anaphylatic rats in a dose-dependently manner. NK-W also inhibited serum histamine levels in OVA-induced AR mice and improved abnormal histological changes such as expansion of grandular cells and hypertrophy of epithelium in the nasal mucosa. These results indicate that Osterici Radix water extract suppress allergic response through downregulation of mast cell activation. Conclusions : This study suggests that a therapeutic potential of Osterici Radix as a source of anti-allergic agents for use in a number of allergic diseases.

Anti-allergic effect of Okbyungpoongsan-Hap-Changijasan

Objectives : In this study, we investigated anti-allergic effect of Okbyeongpungsan-Hap-Changijasan (KOB01) in allergic rhinitis(AR) experimental animals and mast cells. Methods : The potential anti-allergic effect of KOB01 was investigated in a rat model of compound 48/80-induced systemic anaphylactic shock and a mouse of ovalbumin(OVA)-induced AR, and human mast cell line, HMC-1 culture. Each animals were divided into four groups: normal, control, KOB01-treated(100 and 200 mg/kg) and anti-histamine drug, dosodium cromoglycate (DSCG)-treated(50 mg/kg). Animals were orally treated with KOB01 and DSCG and intraperitoneally injected with compound 48/80() or sensitized with 0.1% OVA. The mortality and serum histamine levels were measured in compound 48/80-induced anaphylatic rats. The histological changes in nasal mucosa were investigated in OVA-induced AR mice. Also, mast cell degranulation was observed in compound 48/80-stimulated HMC-1 cells. Results : KOB01 increased mortality and significantly decreased serum histamine levels in compound 48/80-induced anaphylatic rats. The abnormal histological changes such as expansion of grandular cells and hypertrophy of epithelium in nasal mucosa of OVA-induced AR mice was improved by KOB01 treatment nearby a normal group. Therefore, KOB01 inhibited compound 48/80-induced degranulation in HMC-1 cells. Conclusions : These results indicate that KOB01 decrease allergic response through suppressing the mast cell activation in AR and suggest a potential role for KOB01 as a source of anti-allergic agents for use in allergic disorders including of AR.