Flavonone treatment reverses airway inflammation and remodelling in an asthma murine model

Background and Purpose

Asthma is an inflammatory disease that involves airway hyperresponsiveness and remodelling. Flavonoids have been associated to anti-inflammatory and antioxidant activities and may represent a potential therapeutic treatment of asthma. Our aim was to evaluate the effects of the sakuranetin treatment in several aspects of experimental asthma model in mice.

Experimental Approach

Male BALB/c mice received ovalbumin (i.p.) on days 0 and 14, and were challenged with aerolized ovalbumin 1% on days 24, 26 and 28. Ovalbumin-sensitized animals received vehicle (saline and dimethyl sulfoxide, DMSO), sakuranetin (20 mg kg^–1 per mice) or dexamethasone (5 mg kg^–1 per mice) daily beginning from 24th to 29th day. Control group received saline inhalation and nasal drop vehicle. On day 29, we determined the airway hyperresponsiveness, inflammation and remodelling as well as specific IgE antibody. RANTES, IL-5, IL-4, Eotaxin, IL-10, TNF-α, IFN-γ and GMC-SF content in lung homogenate was performed by Bioplex assay, and 8-isoprostane and NF-kB activations were visualized in inflammatory cells by immunohistochemistry.

Key Results

We have demonstrated that sakuranetin treatment attenuated airway hyperresponsiveness, inflammation and remodelling; and these effects could be attributed to Th2 pro-inflammatory cytokines and oxidative stress reduction as well as control of NF-kB activation.

Conclusions and Implications

These results highlighted the importance of counteracting oxidative stress by flavonoids in this asthma model and suggest sakuranetin as a potential candidate for studies of treatment of asthma.     

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.     

Chrysin alleviates allergic inflammation and airway remodeling in a murine model of chronic asthma

Asthma is a chronic airway inflammatory disorder and progresses mainly due to airway remodeling. Chrysin, a natural flavonoid, has been reported to possess multiple biologic activities, including anti-inflammation, anti-oxidation and anti-proliferation. The present study aimed to investigate whether chrysin could relieve allergic airway inflammation and remodeling in a murine model of chronic asthma and the mechanism involved. The female BALB/c mice sensitized and challenged with ovalbumin (OVA) successfully developed airway hyperresponsiveness (AHR), inflammation and remodeling. The experimental data showed that chrysin could alleviate OVA-induced AHR. Chrysin could also reduce OVA-induced increases in the number of inflammatory cells, especially eosinophils, interleukin (IL) -4, and IL-13 in bronchoalveolar lavage fluid (BALF) and total IgE in serum. The decreased interferon-γ (IFN-γ) level in BALF was also upregulated by chrysin. In addition, inflammatory cell infiltration, goblet cell hyperplasia and the expression of α-smooth muscle actin (α-SMA) around bronchioles were suppressed by chrysin. Furthermore, the phosphorylation levels of Akt and extracellular signal-regulated kinase (ERK) could be decreased by chrysin, which are associated with airway smooth muscle cell (ASMC) proliferation. These results indicate the promising therapeutic effect of chrysin on chronic asthma, especially the progression of airway remodeling.     

Mangifera indica L. extract (Vimang) and mangiferin reduce the airway inflammation and Th2 cytokines in murine model of allergic asthma

Objectives The aim was to study the effects of Mangifera indica extract and its major component mangiferin on lung inflammation response and Th2 cytokine production using a murine experimental model of allergic asthma. Methods BALB/c mice were intraperitoneally sensitized with 10 µg of ovoalbumin (OVA) adsorbed on aluminium hydroxide on days 0, 7 and 14. Seven days after the last injection, the mice were challenged with 2% aerosolized OVA inhalation for 30 min beginning on day 21 and continuing until day 24. To evaluate the protective effect, mice were orally treated with M. indica extract (50, 100 or 250 mg/kg) or mangiferin (50 mg/kg) from days 0 to 24. Anti‐OVA immunoglobulin E, interleukin (IL)‐4 and IL‐5 were determined by ELISA and lungs were analysed by histology. Key findings M. indica extract and mangiferin produced a marked reduction of airway inflammation around vessels and bronchi, inhibition of IL‐4 and IL‐5 cytokines in bronchoalveolar lavage fluid and lymphocyte culture supernatant, IgE levels and lymphocyte proliferation. Conclusion This is the first pre‐clinical report of the anti‐inflammatory properties of M. indica extract and mangiferin in experimental asthma and it could be an important part of pre‐clinical requirement necessary for its use to complement the treatment of this complex disease.     

Imiquimod, a toll-like receptor 7 ligand, inhibits airway remodelling in a murine model of chronic asthma

1. Imiquimod, a synthetic Toll-like receptor (TLR) 7 ligand, has been shown to attenuate airway inflammation and airway hyperresponsiveness (AHR) in acute murine models of allergic asthma. In the present study, we investigated the effect of imiquimod on allergen-induced airway remodelling in chronic experimental asthma. 2. Ovalbumin (OVA)-sensitized mice were chronically challenged with aerosolized OVA for 8 weeks. Some mice were exposed to an aerosol of 0.15% imiquimod daily during the period of OVA challenge. Twenty-four hours after the last OVA challenge, mice were evaluated for the development of airway inflammation, AHR and airway remodelling. The levels of total serum IgE and Th2 cytokines (interleukin (IL)-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF) and the expression of transforming growth factor (TGF)-beta1 protein in lungs were measured by ELISA and immunohistochemistry, respectively. 3. The results demonstrated that imiquimod significantly inhibited chronic inflammation, persistent AHR and airway remodelling in chronic experimental asthma. In addition, imiquimod reduced levels of total serum IgE and BALF Th2 cytokines and diminished expression of TGF-beta1 in remodelled airways. 4. In summary, the results of the present study indicate that imiquimod may attenuate the progression of airway inflammation and remodelling, providing potential in the treatment of asthma.     

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.     

Role of endogenous nitric oxide in allergen-induced airway responses in guinea-pigs

1. Endogenous nitric oxide (NO) can be detected in exhaled air and accumulates in inflamed airways. However its physiological role has not been fully elucidated. In this study, we investigated a role for endogenous NO in allergen-induced airway responses. Sensitised guinea-pigs were treated with N^G-nitro-L-arginine methyl ester L-NAME (2.0 mM) or aminoguanidine (AG) (2.0 mM) 30 min before the allergen challenge, and 3 and 4 h after the challenge. Alternatively, L-arginine (2.4 mM) treatment was performed 30 min before, and 2 and 3 h after the challenge. In all groups, ovalbumin (OVA) challenge (2 mg ml⁻¹ for 2 min) was performed, and airway responses, NO production, infiltration of inflammatory cells, plasma exudation and histological details were examined.
2. Allergen-challenged animals showed an immediate airway response (IAR) and a late airway response (LAR), which synchronised with an increase in exhaled NO. Treatment with L-NAME and AG did not affect IAR while they significantly blocked LAR (72% and 80% inhibition compared to vehicle) and production of NO (35% and 40% inhibition). On the other hand, treatment with L-arginine did not affect IAR but potentiated LAR (74% augmentation).
3. In bronchoalveolar lavage (BAL) fluid, allergen-induced increases in eosinophils were reduced by 48% for L-NAME treatment compared to vehicle, and increased by 56% for L-arginine treatment.
4. Treatment with L-NAME significantly decreased airway microvascular permeability to both Monastral blue (MB) and Evans blue (EB) dye (50.6% and 44% inhibition).
5. We conclude that allergen-induced LAR is closely associated with NO production, and that NO plays a critical role in inflammatory cell infiltration and plasma exudation in the allergic condition.

     

Role of adenosine in airway inflammation in an allergic mouse model of asthma

In the present study, we examined dynamic changes in cellular profile of bronchoalveolar lavage (BAL) fluid after adenosine challenge in ragweed sensitized and challenged mice. Mice systemically sensitized and airway challenged with ragweed showed marked airway inflammation manifesting increased eosinophils, lymphocytes, neutrophils and activated macrophages in BAL. Adenosine challenge further enhanced influx of inflammatory cells into BAL, notably neutrophils from 1 to 72 h and eosinophils from 1 to 48 h time-points (p<0.05), which sharply rose at 6-h time-point following adenosine challenge. Greater infiltration of lymphocytes into BAL was observed at 1 and 72 h and macrophages from 6 to 72 h (p<0.05) after adenosine challenge. Accordingly, markers of eosinophils, neutrophils and mast cells were analyzed at 6-h time-point after adenosine challenge. Adenosine challenge significantly increased the levels of eosinophil peroxidase, neutrophil myeloperoxidase and beta-hexosaminidase in BAL. There were more significant effects of adenosine challenge on the degranulation of mast cells in the lung than that in blood. The chemoattractant, eotaxin, was detected in BAL, which increased after adenosine challenge. Theophylline, a non-specific adenosine receptor antagonist, prevented adenosine-enhanced infiltration of inflammatory cells and their respective markers. Our findings suggest that adenosine plays an important role in airway inflammation in an allergic mouse model.     

Ganoderma tsugae in vivo modulates Th1/Th2 and macrophage responses in an allergic murine model

We have reported that Ganoderma tsugae supplementation alleviates bronchoalveolar inflammation in an airway sensitization and challenge model with female BALB/c mice. However, the effects of G. tsugae supplementation in vivo on serum antibody levels, splenocyte and peritoneal microphage immune responses have not yet been determined. In this study, serum antibody levels, cytokines and splenocyte chemical mediators and peritoneal macrophage cultures from ovalbumin (OVA)-sensitized and -challenged mice were examined after continuously consuming G. tsugae supplementation diets for 5 weeks. The results showed that OVA sensitization and challenge significantly (P < 0.05) decreased the spontaneous production of IL-2 (Th1) cytokine, but significantly (P < 0.05) increased spontaneous and OVA-stimulated IL-4 (Th2) production in splenocyte cultures from experimental mice. OVA administration significantly decreased both spontaneous and LPS/IFN-γ-stimulated IL-1β and IL-6 levels in peritoneal macrophage cultures from experimental mice. However, dietary supplementation with G. tsugae significantly increased spontaneous IL-2 level, but slightly decreased spontaneous IL-4 level in cultured splenocyte supernatants in the experimental groups. G. tsugae supplementation enhanced pro-inflammatory cytokines IL-1β and IL-6 production in cultured peritoneal macrophages. However, the nitric oxide level from cultured peritoneal macrophages and serum OVA-specific IgE and IgG_2a antibody levels was not significantly affected. These results suggest that OVA sensitization and challenge induced a Th2-skewed splenocyte response and decreased peritoneal macrophage cytokine secretion. G. tsugae supplementation in vivo modulated the Th1/Th2 balance and enhanced macrophage immune responses. However, the supplementation diet could not fully reverse the Th2-skewed responses to level of Th1-skewed responses.     

Abietic acid attenuates allergic airway inflammation in a mouse allergic asthma model

Abietic acid (AA), one of the terpenoids isolated from Pimenta racemosa var. grissea, has been reported to have anti-inflammatory and immunomodulatory effects. However, the anti-allergic effects of AA remain unclear. The aim of this study was to investigate the anti-allergic effects of AA in an ovalbumin (OVA)-induced asthma murine model. The model of mouse asthma was established by induction of OVA. AA (10, 20, 40 mg/kg) was administered by oral gavage 1 h after the OVA treatment on days 21 to 23. At 24 h after the last challenge, bronchoalveolar lavage fluid (BALF) and lung tissues were collected to assess pathological changes, cytokines production, and NF-κB expression. The results showed that AA attenuated lung histopathologic changes, inflammatory cells infiltration, and bronchial hyper-responsiveness. AA also inhibited OVA-induced the nitric oxide (NO), IL-4, IL-5, IL-13, and OVA-specific IgE production, as well as NF-κB activation. In conclusion, the current study demonstrated that AA exhibited protective effects against OVA-induced allergic asthma in mice and the possible mechanism was involved in inhibiting NF-κB activation.     

Modulatory effect of anisodamine on airway hyper-reactivity and eosinophilic inflammation in a murine model of allergic asthma

Anisodamine, a peripheral muscarinic receptor antagonist, is a naturally occurring atropine derivative that has been isolated, synthesized and characterized by scientists in China. In the present investigation, we evaluated the modulatory effects of anisodamine on airway hyper-reactivity and inflammation in a murine model of allergic asthma. Asthma model was induced successfully by ovalbumin. The activation of cells, airway eosinopilia, cytokine production, and airway function were examined. Our results collectively show that anisomanine could significantly suppress the accumulation of eosinophils into the airways and dramatically inhibited the histological changes in OVA-induced mice. Additionally, anisodamine could restore the Th1/Th2 balance in BALF by downregulating the level of Th2 cell-associated cytokine IL-4 (p<0.01) and upregulating the level of Th1 cell-associated cytokine IFN-γ (p<0.01). In addition, pretreatment with anisodamine also showed strong suppression of allergen-induced bronchial hyper-reactivity with maximum contraction decreasing from 0.45 ± 0.02 g to 0.28 ± 0.03 g (p<0.01). These results suggested the modulatory effects of anisodamine on Th1/Th2 balance by enhancing Th1-related and suppressing Th2-related parameters, as well as its potential application in airway hyper-reactivity and eosinophilic inflammation.     

Britanin attenuates ovalbumin-induced airway inflammation in a murine asthma model

We previously demonstrated the alleviation of ovalbumin (OVA)-induced airway inflammation by Inulae flos. In the present study, the effects of britanin, a sesquiterpene compound isolated from Inulae flos, were evaluated in an in vivo animal model for anti-asthma activity through observation of airway hyperresponsiveness (AHR), eosinophil recruitment, Th2 cytokine and IgE levels, and lung histopathology. Britanin administration effectively reduced AHR induced by aerosolized methacholine, airway eosinophilia, Th2 cytokines in bronchoalveolar lavage fluids and the supernatant of cultured splenocytes compared with OVA-induced mice. Histological studies showed that increased inflammatory cell infiltration and mucus secretion were reduced by britanin administration. Thus, britanin may have therapeutic potential for treating allergic asthma.     

Ginger prevents Th2-mediated immune responses in a mouse model of airway inflammation

It is well documented that compounds from rhizomes of Zingiber officinale, commonly called ginger, have anti-inflammatory properties. Here, we show that ginger can exert such functions in vivo, namely in a mouse model of Th2-mediated pulmonary inflammation. The preparation of ginger aqueous extract (Zo.Aq) was characterized by mass spectrometry as an enriched fraction of n-gingerols. Intraperitoneal injections of this extract before airway challenge of ovalbumin (OVA)-sensitized mice resulted in a marked decrease in the recruitment of eosinophils to the lungs as attested by cell counts in bronchoalveolar lavage (BAL) fluids and histological examination. Resolution of airway inflammation induced by Zo.Aq was accompanied by a suppression of the Th2 cell-driven response to allergen in vivo. Thus, IL-4, IL-5 and eotaxin levels in the lungs as well as specific IgE titres in serum were clearly diminished in ginger-treated mice relative to their controls after allergen sensitization and challenge. Finally, we found that [6]-gingerol, a major constituent of ginger, was sufficient to suppress eosinophilia in our model of inflammation. This is the first evidence that ginger can suppress Th2-mediated immune responses and might thus provide a possible therapeutic application in allergic asthma.     

Inhibition of airway inflammation, hyperresponsiveness and remodeling by soy isoflavone in a murine model of allergic asthma

Epidemiologic studies have associated higher dietary consumption of soy isoflavones with decreased self-report of cough and allergic respiratory symptoms, but the pharmacodynamic effects of soy isoflavone on asthmatic model have not been well-described. Here, we hypothesized that soy isoflavone may have potential effects on airway hyperresponsiveness, inflammation and airway remodeling in a murine of asthma. Mice sensitized and challenged with ovalbumin developed airway inflammation. Bronchoalveolar lavage fluid was assessed for inflammatory cell counts, and for cytokine levels. Lung tissues were examined for cell infiltration, mucus hypersecretion and airway remodeling, and for the expression of inflammatory biomarkers. Airway hyperresponsiveness was monitored by direct airway resistance analysis. Oral administration of soy isoflavone significantly reduced ovalbumin-induced airway hyperresponsiveness to intravenous methacholine, and inhibited ovalbumin-induced increases in eosinophil counts. RT-PCR analysis of whole lung lysates revealed that soy isoflavone markedly suppressed ovalbumin-induced mRNA expression of eotaxin, interleukin(IL)-5, IL-4 and matrix metalloproteinase-9, and increased mRNA expression of interferon (IFN)-γ and tissue inhibitor of metalloproteinase-1 in a dose-dependent manner. Soy isoflavone also substantially recovered IFN-γ/IL-4 (Th1/Th2) levels in bronchoalveolar lavage fluid. In addition, histologic studies showed that soy isoflavone dramatically inhibited ovalbumin-induced lung tissue eosinophil infiltration, airway mucus production and collagen deposition in lung tissues. Our findings suggest that soy isoflavone as nutritional supplement may provide a novel means for the treatment of airway inflammatory disease.     

Obesity enhances eosinophilic inflammation in a murine model of allergic asthma

Background and purpose:

Obesity is associated with deterioration in asthma outcomes. Although airways eosinophil accumulation is characteristic of lung allergic diseases, little is known about the influence of obesity on the allergic eosinophil trafficking from bone marrow to lung tissues, and recruitment to airways lumen. Here, we have assessed the effects of diet-induced obesity on allergic eosinophilic inflammation in mice, examining eosinophil trafficking from bone marrow to airways, and production of T_H1/T_H2 cytokines.

Experimental approach:

C57BL/6 mice fed for 10 weeks with standard chow or high-fat diet were sensitized and challenged with ovalbumin. At 24–96 h post-ovalbumin challenge, bronchoalveolar lavage (BAL) fluid, lung tissue and bone marrow were examined.

Key results:

The high-fat-fed mice exhibited increased body weight and epididymal fat, glucose intolerance and alterations in lipid profile compared with the lean mice. Obesity markedly elevated serum leptin and lowered adiponectin levels. Ovalbumin challenge in obese mice promoted a markedly higher eosinophil accumulation in bone marrow and connective tissue surrounding the bronchial and bronchiolar segments. Eosinophil number in BAL fluid of obese mice was lower at 24 and 48 h. Levels of interleukin (IL)-5, eotaxin, tumour necrosis factor-α and IL-10 in BAL fluid of obese mice were significantly higher than in lean mice.

Conclusions and implications:

Diet-induced obesity enhanced eosinophil trafficking from bone marrow to lung tissues, and delayed their transit through the airway epithelium into the airway lumen. Consequently, eosinophils remain longer in lung peribronchiolar segments due to overproduction of T_H1/T_H2 cytokines and chemokines.     

CpG-ODN对哮喘小鼠Th1/Th2相关细胞因子表达的影响

目的：探讨CpG-ODN对哮喘小鼠Th1/Th2相关细胞因子的调节作用及气道炎症的抑制作用。方法：采用酶联免疫中附法（ELISA）分别检测CpG-ODN对哮喘小鼠抗原首次激发后24小时和抗末次激发后24小时血清及支气管肺泡灌洗液（BALF）中Th2细胞因子IL－4和Th1细胞因子IFNγ水平的影响，并与激素治疗组和哮喘组对照。结果：（1）抗原末次激发后24小时，CpG-ODN 血清及BALF中IFNγ水平高于哮喘组及地塞米松组（P＜0．001）。（2）抗原首次激发后24小时及抗原末次激发后24小时血清和BALF中IL－4水平低于哮喘组（P＜0．05），与地塞米松组比较无显著性差异（P＞0．05）。（3）抗原末次激发后24小时，CpG-ODN组外周血和BALF中嗜酸性粒细胞计数均低于哮喘组（P＜0．001）。结论：CpG-ODN不仅有具有与地塞米松相同的下调Th2细胞因子表达和抑制嗜酸性粒细胞的作用，而且还具有地塞米松所没有的诱导Th1细胞因子表达的作用。说明其可能通过调节Th1/Th2平衡而达到在早期抑制哮喘发病的目的。     

The triterpenoid lupeol attenuates allergic airway inflammation in a murine model

Asthma is a chronic inflammatory disease of the airways associated with a Th2 immune response. Despite their side effects, corticosteroids are the most used and effective drugs for treatment of asthma. In this work we investigated the efficacy of lupeol, a triterpenoid isolated from Diplotropis ferruginea Benth. (Fabaceae), in the treatment of bronchial asthma in BALB/c mice immunized with ovalbumin. Administration of lupeol caused the reduction of cellularity and eosinophils in the bronchoalveolar lavage fluid. Treatment with lupeol also reduced the production of mucus and overall inflammation in the lung. Levels of Type II cytokines IL-4, IL-5 and IL-13 were significantly reduced in mice treated with lupeol, an effect that was similar to that observed in dexamethasone-treated mice. In contrast, IgE production was not significantly altered after treatment with lupeol. In conclusion, our results demonstrate that lupeol attenuates the alterations' characteristics of allergic airway inflammation. The investigation of the mechanisms of action of this molecule may contribute for the development of new drugs for the treatment of asthma.     

Kochia scoparia fruit attenuates allergic airway inflammation in ovalbumin (OVA)-induced murine asthma model

Kochia scoparia fruit has been used in Asia for a long time. It possesses anti-inflammatory, antiallergic, and antipruritic actions. We investigated the role of a K. scoparia fruit ethanolic extract (KSEE) in allergic airway inflammation in a mouse asthma model. BALB/c mice were sensitized with ovalbumin (OVA) and, upon OVA aerosol challenge, developed airway eosinophilia, mucus hypersecretion, elevations in cytokine, chemokine, and immunoglobulin levels, and upregulation of MMP-9, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) expression. Intragastric administration of KSEE significantly attenuated OVA-induced influx of total leukocytes, eosinophils, neutrophils, macrophages, and lymphocytes into lungs, as well as attenuating levels of interleukin (IL)-4 and IL-5 in a dose-dependent manner. KSEE also significantly reduced the serum levels of total and OVA-specific immunoglobulin (Ig)E and OVA-specific IgG1 release into the airspace. Histological studies showed that KSEE inhibited OVA-induced lung tissue eosinophilia and airway mucus production. Moreover, in whole lung tissue lysates, immunoreactivity showed that KSEE markedly attenuated the OVA-induced increase in expression of ICAM-1, VCAM-1, and MMP-9. These results show that KSEE possesses protective effects against allergic airway inflammation, acts as an MMP-9 inhibitor, and induces a reduction in ICAM-1 and VCAM-1 expression.     

Shikonin inhibits maturation of bone marrow-derived dendritic cells and suppresses allergic airway inflammation in a murine model of asthma

BACKGROUND AND PURPOSE

Shikonin exhibits a wide range of anti-inflammatory actions. Here, we assessed its effects on maturation of murine bone marrow-derived dendritic cells (BM-DCs) and on allergic reactions in a murine model of asthma.

EXPERIMENTAL APPROACH

Cultured murine BM-DCs were used to investigate the effects of shikonin on expression of cell surface markers and their stimulation of T-cell proliferation and cytokine production. The therapeutic potential of shikonin was evaluated in a model of allergic airway disease.

KEY RESULTS

Shikonin dose-dependently inhibited expression of major histocompatibility complex class II, CD80, CD86, CCR7 and OX40L on BM-DCs, induced by a mixture of ovalbumin (OVA; 100 µg·mL⁻¹) and thymic stromal lymphopoietin (TSLP; 20 ng·mL⁻¹). Shikonin-treated BM-DCs were poor stimulators of CD4⁺ T lymphocyte and induced lower levels of interleukin (IL)-4, IL-5, IL-13 and tumour necrosis factor (TNF)-α release by responding T-cells. After intratracheal instillation of shikonin in OVA-immunized mice, OVA challenge induced lower IL-4, IL-5, IL-13, TNF-α and eotaxin release in bronchial alveolar lavage fluid, lower IL-4 and IL-5 production in lung cells and mediastinal lymph node cells and attenuated OVA-induced lung eosinophilia and airway hyperresponsiveness.

CONCLUSION AND IMPLICATIONS

Shikonin effectively suppressed OVA + TSLP-induced BM-DC maturation in vitro and inhibited allergic inflammation and airway hyperresponsiveness in a murine model of asthma, showing good potential as a treatment for allergic asthma. Also, our model provides a novel platform for screening drugs for allergic diseases.