Inhibitory effects of Actinidia polygama extract and cyclosporine A on OVA-induced eosinophilia and bronchial hyperresponsiveness in a murine model of asthma

Actinidia polygama is one of the well known herb used in oriental medicine for treatment of anti-inflammatory and many allergic diseases. Anti-asthmatic effects of A. polygama in the development of OVA-induced eosinophilia and hyperresponsiveness in murine model of asthma have not been fully investigated in vivo. Cyclosporine A (CsA) has been shown to inhibit single allergen-induced allergic inflammation such as eosinophilic and lymphocytic infiltration and mRNA expression for interleukin (IL)-4 and IL-5. Asthma is a chronic inflammatory disease of the mucosa and is associated with excess production of Th2 cytokines and eosinophil influx in lung. To clarify the anti-inflammatory and anti-asthmatic effects of A. polygama and CsA, we examined the influence of A. polygama fructus extract (APF) and CsA on the development of pulmonary eosinophilic inflammation in murine model of asthma. Our results have shown that APF and CsA have profound inhibitory effects on the accumulation of eosinophills into airways, with the reduction of eosinophil and total lung leukocyte number by reducing IL-4, IL-5, IL-13 and IgE levels in the BALF. Moreover, APF decreased eosinophil CCR3 expression and CD11b expression in lung cells. These results indicate that APF has a deep inhibitory effect on airway inflammation and hyperresponsiveness in murine model of asthma and play a crucial role as an immunomodulator which possess anti-inflammatory and anti-asthmatic property by modulating the relationship between Th1/Th2 cytokine imbalance.     

Anti-asthmatic effect of schizandrin on OVA-induced airway inflammation in a murine asthma model

Asthma comprises a triad of reversible airway obstruction, bronchial smooth muscle cell hyperreactivity to bronchoconstrictors, and chronic bronchial inflammation. Clinical and experimental findings have established eosinophilia as a sign of allergic disorders. In the present investigation, we evaluated the anti-asthmatic effects of schizandrin and its underlying mechanisms in an in vivo murine asthmatic model. To accomplish this, female BALB/c mice were sensitized and challenged with ovalbumin (OVA), and examined for the following typical asthmatic reactions: increased numbers of eosinophils and other inflammatory cells in bronchoalveolar lavage fluid (BALF); production of Th1 cytokines (such as tumor necrosis factor (TNF)-α in BALF); production of Th2 cytokines (such as interleukin IL-4 and IL-5) in BALF; presence of total and OVA-specific immunoglobulins (Ig)E in serum; presence of oxidative stress; hyperplasia of goblet cells in the lung; and marked influx of inflammatory cells into the lung. Our results collectively show that schizandrin exerts profound inhibitory effects on accumulation of eosinophils into the airways and reduces the levels of IL-4, IL-5, IFN-γ, and TNF-α in BALF. Additionally, schizandrin suppresses the production of reactive oxygen species (ROS) in a dose-dependent manner, and inhibits goblet cell hyperplasia and inflammatory cell infiltration in lung tissue. Thus, schizandrin has anti-asthmatic effects, which seem to be partially mediated by reduction of oxidative stress and airway inflammation, in a murine allergic asthma model. These results indicate that schizandrin may be an effective novel therapeutic agent for the treatment of allergic asthma.     

Administration of mycobacterial Ag85A and IL-17A fusion protein attenuates airway inflammation in a murine model of asthma

Interleukin (IL)-17A contributes to the development of asthma, especially in severe asthma which has characteristic neutrophil infiltration in airways. However, IL-17A-blocking antibody could escalate T helper (Th) 2 cytokines, such as IL-13, IL-4 in murine models. We aimed at determining the effect of mycobacterial Ag85A and IL-17A fusion protein—Ag85A-IL-17A on airway inflammation in a murine model of asthma. IL-17A recombinant protein fused mycobacterial immunodominant antigen Ag85A was constructed, expressed and purified. The fusion protein was then administrated into BALB/c mice and its anti-inflammatory effects in the infiltration of inflammatory cells, Th2/Th17 cytokines in BALF, histopathological changes of lung tissues as well as chemokines in lung tissues were evaluated in the murine model of asthma. We found that administration of mycobacterial Ag85A and IL-17A fusion protein induced IL-17A specific immunoglobulin (Ig)G in sera and significantly decreased IL-17A and IL-6 levels in bronchoalveolar lavage fluid (BALF). Ag85A-IL-17A vaccinated mice also showed marked reduction in the infiltration of inflammatory cells in peribronchiolar region and significant decrease in total cells, eosinophil cells and neutrophil cells in BALF. The increased levels of IL-13 and IL-4 in BALF of ovalbumin-sensitized mice were significantly reduced by the administration of Ag85A-IL-17A. Furthermore, CD3⁺CD4⁺IL-13⁺ splenocytes stimulated with OVA and CXCL1 mRNA, CCL2 mRNA and GATA-3 mRNA expressed in lung tissues were decreased markedly in Ag85A-IL-17A vaccinated group. Our results demonstrate remarkable antiallergic effects of Ag85A-IL-17A in a murine model of asthma and it may have protective effects on allergic asthma.     

A novel pentapeptide originated from calf thymus named TIPP shows an inhibitory effect on lung allergic inflammation

Thymic immunosuppressive pentapeptide (TIPP) is a novel pentapeptide originally obtained from calf thymic immunosuppressive extract. In this study we aimed to investigate the anti-inflammatory effect and mechanisms of TIPP in vivo with an ovalbumin-induced mouse allergic asthma model. We investigated the effects of TIPP on the infiltration of inflammation cells, immune cell subtypes, Th2 cytokines in BALF and IgE in serum, mRNA levels of IL-4, IL-10, TNF-α and eotaxin-1, expression of MCP-1, VCAM-1 and COX-2, and activation of MAP kinases and NF-κB. Our results showed that TIPP significantly inhibited the increase in Th2 cytokines and OVA-specific IgE production, mRNA levels of IL-4, TNF-α and eotaxin-1 and the expression of MCP-1, VCAM-1 and COX-2 in lung tissues, as well effectively resisting the balance changes of cells in BALF. In addition, it was found that the administration of TIPP attenuated the activation of MAP kinases and NF-κB in the lung tissues of the allergic mice. Our data suggest that TIPP effectively suppresses the allergic and inflammatory responses in allergic mice via blocking MAP kinases/NF-κB signalling pathway. The investigation indicated that TIPP may become an anti-allergic and anti-inflammatory drug.     

The effects of chrysophanol on ovalbumin (OVA)-induced chronic lung toxicology by inhibiting Th17 response

Chrysophanol (CH), extracted from plants of Rheum genus, possesses various pharmacological effects including anti-inflammatory activity. The purpose of the present study was to evaluate the protective effects and the underlying mechanisms of CH on ovalbumin (OVA)-induced asthma in mice. Fifty mice were randomly assigned to five experimental groups: control group, model group, dexamethasone (2?mg/kg) group and CH (5 and 10?mg/kg) groups. The number of eosinophil cells and the production of interleukin-6 (IL-6), IL-1β, IL-17?A and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF) were measured. In addition, pulmonary histopathology, airway resistance (Raw), T-helper17 (Th17) cells frequency and RORγt expression were evaluated. Our study demonstrated that CH effectively decreased eosinophil count and inflammatory cytokines production in BALF. In addition, treatment with CH significantly inhibited the Raw, Th17 percentage and RORγt expression in OVA-induced animals compared with those in model group. Histological studies also demonstrated that CH significantly suppressed OVA-induced eosinophilia in lung tissue compared with model group. Our findings supported that CH can prevent allergic asthma in the mouse model.     

Tiarellic acid attenuates airway hyperresponsiveness and inflammation in a murine model of allergic asthma

Asthma is a persistent inflammatory disease characterized by airway obstruction and hyperresponsiveness in association with airway inflammation. In the current research, we studied the anti-inflammatory and anti-asthmatic effects of tiarellic acid (TA) isolated from Tiarella polyphylla, based on asthmatic parameters, such as immunoglobulin E (IgE) level, cytokine release, eosinophilia, airway hyperresponsiveness (AHR), reactive oxygen species (ROS) and mucus hypersecretion, in an ovalbumin (OVA)-sensitized/challenged mouse model. TA significantly inhibited increases in IgE, levels of ROS and T helper cytokines, such as interleukin (IL)-4, IL-5, TNF-α, and IL-13, in bronchoalveolar lavage fluid (BALF), and effectively suppressed airway hyperresponsiveness, eosinophilia, and mucus hypersecretion in the asthmatic mouse model. In addition, we found that administration of TA attenuated ovalbumin-induced increases in NF-κB activity in lungs. The efficacy of TA was comparable to that of montelukast, a currently available anti-asthmatic drug. Our results support the utility of TA as a herbal medicine for asthma treatment and may have application in the development of anti-inflammatory and anti-asthmatic drugs.     

DA-9201 shows anti-asthmatic effects by suppressing NF-кB expression in an ovalbumin-lnduced mouse model of asthma

Nuclear factor kappa B (NF-kappaB) regulates the expression of multiple cytokines, chemokines, and cell adhesion molecules that are involved in the pathogenesis of asthma. We investigated the anti-asthmatic effects and the mechanism of action of DA-9201, an extract of the black rice, in a mouse model of asthma. Mice immunized with ovalbumin (OVA) were administered with DA-9201 (30, 100 or 300 mg/kg) or dexamethasone (DEXA, 3 mg/kg) for 2 weeks and challenged with aerosolized OVA during the last 3 days. Anti-asthmatic effects were assessed by means of enhanced pauses, level of total IgE and Th2 cytokines in plasma or bronchoalveolar lavage fluid (BALF), the percentage of eosinophils in BALF, and histopathological examination. The expression of NF-kappaB in nuclear and cytoplasmic fraction and its DNA-binding activity in lung tissues were analyzed by means of Western blotting and electrophoretic gel mobility shift assay (EMSA), respectively. DA-9201 significantly reduced airway hyperresponsiveness (AHR), total IgE level in plasma and BALF, IL-4, IL-5, and IL-13 levels in BALF, and the percentage of eosinophils in BALF. Tissue inflammation was significantly improved by DA-9201 treatment. In addition, DA-9201 dramatically suppressed the expression of NF-kappaB and its DNA-binding activity. These results suggest that DA-9201 may be useful for the treatment of asthma and its efficacy is related to suppression of NF-kappaB pathway.     

Suppressive Effect of Carnosol on Ovalbumin-Induced Allergic Asthma

Asthma is a chronic obstructive lung disease characterized by recurrent episodes of bronchoconstriction and wheezing. Conventional asthma treatment involves the suppression of airway inflammation or improving airway flow. Rosmarinus officialis, also known as rosemary, is a Mediterranean plant that is used for the treatment of inflammatory diseases. Carnosol, a diterpenoid found in rosemary extracts, has been known to exhibit anti-inflammatory, anti-tumor, and anti-oxidant effects. The effect of carnosol on allergic responses has not been tested yet. The effect of carnosol on a murine allergic asthma model were investigated. Carnosol inhibited the degranulation of RBL-2H3 mast cells. Carnosol treatment inhibited the increase in the number of eosinophils in the bronchoalveolar lavage fluids (BALF) of mice treated with ovalbumin. Carnosol treatment also inhibited inflammatory responses and mucin production in histologic studies. Carnosol treatment inhibited the increases of IL-4 and IL-13 cytokines expression in both BALF and the lungs. These results suggest that carnosol may have a potential for allergic asthma therapy.     

Therapeutic effects of rosmarinic acid on airway responses in a murine model of asthma

Rosmarinic acid (RA) is an active component of a traditional Chinese herbal medicine. Previously, we reported that RA exerted a strong anti-inflammatory effect in a mouse acute lung injury model. Therefore, we hypothesized that RA might also have potential therapeutic effects in a murine model of asthma. In this study, we aimed to evaluate the anti-asthmatic activity of RA and explored its possible molecular mechanisms of action. Female BALB/c mice that had been sensitized to and challenged with ovalbumin (Ova) were treated with RA (20 mg/kg) 1 h after challenge. The results showed that RA greatly diminished the number of inflammatory cells and the production of Th2 cytokines in the bronchoalveolar lavage fluid (BALF); significantly reduced the secretion of total IgE, Ova-specific IgE, and eotaxin; and markedly ameliorated airway hyperresponsiveness (AHR) compared with Ova-induced mice. Histological studies further revealed that RA substantially decreased inflammatory cells infiltration and mucus hypersecretion compared with Ova-induced mice. Moreover, our results suggested that the protective effects of RA were mediated by the inhibition of JNK and p38 MAPK phosphorylation and nuclear factor-κB (NF-κB) activation. Furthermore, RA treatment resulted in a significant reduction in the mRNA expression of AMCase, CCL11, CCR3, Ym2 and E-selectin in lung tissue. These findings suggest that RA may effectively delay the development of airway inflammation and could thus be used as a therapy for allergic asthma.     

Effect of MX-68 on airway inflammation and hyperresponsiveness in mice and guinea-pigs

MX-68 is a newly synthesized antifolate, which is a derivative of methotrexate (MTX). In this paper, the effect of MX-68 on allergic airway responses in mice and guinea-pigs was studied. In the first experiment, antigen-induced airway inflammation and airway hyperresponsiveness (AHR) to acetylcholine in mice were examined and compared with the effects of classical antifolate methotrexate and prednisolone. Mice were sensitized with ovalbumin as an antigen and challenged with ovalbumin inhalation three times. After the last inhalation, AHR and airway inflammation were observed. An increase in Th2 cytokines (IL-4 and IL-5) and a decrease in a Th1 cytokine (IFN-gamma) in the bronchoalveolar lavage fluid (BALF), as well as an elevation of the immunoglobulin level in serum, were observed in sensitized mice. Oral administration of MX-68 had no effect on changes of body weight, but prednisolone reduced body weight during the experiment. The antigen-induced AHR and increases in the number of eosinophils and lymphocytes in BALF were significantly inhibited by MX-68. MX-68 interfered with the elevation of IL-4 and IL-5 levels in BALF, but had no effect on the decrease in IFN-gamma. Moreover, MX-68 significantly inhibited the elevation of serum IgE and IgG levels. In the guinea-pig model for bronchial asthma, biphasic increases in airway resistance (immediate asthmatic response, IAR, and late asthmatic response, LAR), as well as accumulated inflammatory cells in BALF, were observed after repeated antigen challenge. These asthmatic responses and inflammatory signs were significantly decreased by administration of MX-68. These results suggest that MX-68 obviously has an anti-inflammatory effect in an animal model of asthma and would be useful clinically for the treatment of bronchial asthma.     

Anti-inflammatory effects of low-molecular weight chitosan oligosaccharides in IgE-antigen complex-stimulated RBL-2H3 cells and asthma model mice

The anti-inflammatory effects of low-molecular weight chitosan oligosaccharides (LM-COS) prepared from high-molecular weight chitosan by enzymatic digestion were investigated against allergic reaction and allergic asthma in vivo and in vitro. Allergic asthma is an inflammatory disease of the airways associated with enhanced degranulation and cytokine generation. The LM-COS (<1 kDa), consisting of glucosamine (GlcN)(n), n=3-5, were capable of inhibiting both antigen-stimulated degranulation and cytokine generation in rat basophilic leukemia RBL-2H3 cells. The protective effect of LM-COS against ovalbumin (OVA)-induced lung inflammation in asthma model mice was also examined. Oral administration of LM-COS (16 mg/kg body weight/day) resulted in a significant reduction in both mRNA and protein levels of interleukin (IL)-4, IL-5, IL-13, tumor necrosis factor (TNF)-α in the lung tissue and bronchoalveolar lavage fluid (BALF); The protein levels of IL-4, IL-13 and TNF-α in BALF were decreased by 5.8-fold, 3.0-fold and 9.9-fold, respectively, compared to those in the OVA-sensitized/challenged asthma control group. These results suggest that the oral administration of LM-COS is effective in alleviating the allergic inflammation in vivo and thus can be a good source material for the development of a potent therapeutic agent against mast cell-mediated allergic inflammatory responses and airway inflammation in allergic inflammatory diseases, including asthma.     

Ganoderma tsugae supplementation alleviates bronchoalveolar inflammation in an airway sensitization and challenge mouse model

Ganoderma tsugae (a Chinese mushroom Songshan lingzhi) cultivated in Taiwan is extensively used in Chinese traditional medicine to treat different diseases. To determine whether G. tsugae has anti-inflammatory effects on bronchoalveolar inflammation in vivo, we investigated the anti-inflammatory effects of G. tsugae products, YK01 and YK07, on bronchoalveolar inflammation using an airway sensitization and challenge mouse model. Female BALB/c mice were weekly sensitized by intraperitoneal injection of ovalbumin (OVA) three times and challenged with aerosolized OVA twice. Differential cell counts of infiltrating leukocytes, inflammatory mediators, cytokines in bronchoalvelor lavage fluid (BALF) of OVA-challenged mice were examined after continuously consuming G. tsugae diets for 5 weeks. We found that supplementation of G. tsugae significantly decreased total infiltrating leukocytes and lymphocyte percentage in BALF in the experimental groups. Supplementation of G. tsugae also significantly reduced inflammatory mediators in BALF including histamine, prostaglandin E2, eotaxin, and protein levels, however the levels of pro-inflammatory cytokines, interleukin (IL)-1beta and IL-6, in BALF did not significantly change. These results suggest that both G. tsugae supplementation diets YK01 and YK07 might alleviate bronchoalveolar inflammation via decreasing the infiltration of inflammatory cells and the secretion of inflammatory mediators into the local tissues of lungs and airways. Further, these results indicate that the relief of bronchoalveolar inflammation in an airway sensitization murine model provides a possible therapeutic application for G. tsugae in allergic asthma.     

麻芩消咳颗粒平喘消炎作用研究

目的探讨麻芩消咳颗粒的平喘抗炎作用。方法SD大鼠随机分为6组,分别为肺宁颗粒2.5 g·kg^-1组、麻芩消咳颗粒(1、2、4 g·kg^-1)组、模型组和溶剂对照组。第0、7天皮下注射卵蛋白混悬液致敏。第15天开始给药并用1%的OVA溶液激发哮喘,每天给药1次,连续给药4周。给药结束后检测大鼠肺泡盥洗液中白细胞介素6(IL-6)、白细胞介素17(IL-17)含量及血清中免疫球蛋白E(IgE)、白细胞介素4(IL-4)水平,观察肺组织病理学变化,Western blot检测肺组织中PI3K、p-PI3K、AKT、p-AKT的表达水平。结果麻芩消咳颗粒2 g·kg^-1能够降低大鼠肺泡盥洗液中白细胞介素6、白细胞介素17含量及血清中免疫球蛋白E、白细胞介素4水平,降低PI3K、ATK磷酸化水平。结论麻芩消咳颗粒对卵蛋白诱发的大鼠过敏性哮喘模型有显著的平喘抗炎作用,与PI3K/AKT调节的炎症信号通路有关。     

Inhibitory effect of DA-9201, an extract of Oryza sativa L., on airway inflammation and bronchial hyperresponsiveness in mouse asthma model

Asthma is one of the major public health problems worldwide and the morbidity and mortality of asthma has increased in the past two decades. Accumulating data suggest that unnecessary immune responses and inflammation should be suppressed to treat asthma. The purpose of this study is to investigate the anti-asthmatic effects of DA-9201, an ethanolic extract of black rice (Oryza sativa L. var japonica), on an ovalbumin (OVA)-induced mouse model of asthma. Balb/c mice immunized with OVA were administered with DA-9201 (30, 100 or 300 mg/kg, p.o.) or dexamethasone (3 mg/kg, p.o.) and challenged with 1% aerosolized OVA for 30 min. The effects on airway inflammation, airway hyperresponsiveness (AHR), antibody profiles and cytokines were evaluated. DA-9201 treatment significantly reduced the number of eosinophils in bronchoalveolar lavage fluid (BALF) and ameliorated the AHR. Lung histological features also showed that DA-9201 reduced airway inflammation. Furthermore, DA-9201 treatment decreased IFN-gamma as well as IL-4, IL-5 and IL-13 levels in the supernatant of cultured splenocytes, and suppressed the level of OVA-specific IgG, IgG2a, IgG1 and total IgE in plasma. DA-9201 showed anti-asthmatic effects by suppressing unnecessary immune responses, airway inflammation, eosinophilia, AHR and IgE level. These results suggest DA-9201 might be beneficial for the treatment of asthma.     

Narirutin inhibits airway inflammation in an allergic mouse model

1. Flavonoids are naturally occurring compounds that possess anti-allergic, anti-inflammatory, antiproliferative and anti-oxidant properties. In the present study, we investigated whether the flavonoid narirutin could reduce airway inflammation in ovalbumin (OVA)-sensitized/challenged NC/Nga mice, a model of allergic eosinophilic airway inflammation. 2. Mice were initially immunized intraperitoneally with OVA on Days 0 and 7 and then challenged with inhaled OVA on Days 14, 15 and 16. In addition, some mice received narirutin orally at doses of 0.1, 1 or 10 mg/kg bodyweight daily on Days 7-16. 3. At 10 mg/kg, but not 0.1 or 1 mg/kg, narirutin significantly diminished OVA-induced airway inflammation caused by infiltration of lung tissue with inflammatory and mucus-producing cells, as well as reduced eosinophil counts in the peripheral blood and bronchoalveolar lavage fluid (BALF), interleukin (IL)-4 levels in BALF and IgE levels in serum. 4. The mechanism of the anti-inflammatory effect of narirutin are likely to be associated with a reduction in the OVA-induced increases of IL-4 and IgE in a murine model of allergic eosinophilic airway inflammation. These findings suggest that narirutin may be an effective new tool in the treatment of bronchial asthma.     

Anti-inflammatory and anti-asthmatic effects of resveratrol,a polyphenolic stilbene,in a mouse model of allergic asthma

Asthma is an inflammatory disease of the airways, and the current focus in managing asthma is the control of inflammation. Resveratrol (3,4,5-trihydroxystilbene) is a polyphenolic stilbene found in the skins of red fruits, including grapes, that may be responsible for some of the health benefits ascribed to consumption of red wine. We investigated the suppressive effects of resveratrol on asthmatic parameters such as cytokine release, eosinophilia, airway hyperresponsiveness, and mucus hypersecretion, in an OVA-induced allergic mouse model of asthma. Resveratrol significantly inhibited increases in T-helper-2-type cytokines such as IL-4 and IL-5 in plasma and bronchoalveolar lavage fluid (BALF), and also effectively suppressed airway hyperresponsiveness, eosinophilia, and mucus hypersecretion, in the asthmatic mouse model. The efficacy of resveratrol was similar to that of dexamethasone, a glucocorticoid used as a positive control. These results suggest that resveratrol may have applications in the treatment of bronchial asthma.