Anthocyanins inhibit airway inflammation and hyperresponsiveness in a murine asthma model
Introduction
Bronchial asthma is an inflammatory disease of the airways, characterized by eosinophilia, mucus hypersecretion and airway hyperresponsiveness (AHR). Oxidative stress may play an important role in the pathogenesis of asthma such as enhancing AHR, mucus secretion, and bronchoconstriction (Talati et al., 2006). Superoxide dismutase (SOD) activity was lower in asthmatic individuals than that seen in healthy controls (Comhair et al., 2000). In population-based study, a higher intake of selenium and apples may protect against asthma, and a higher consumption of red wine might reduce asthma severity in some individuals (Shaheen et al., 2001). In addition, vitamin C and E have been shown to decrease the severity of pollutant-induced bronchial responsiveness (Trenga et al., 2001).
Anthocyanins are natural pigments that belong to the flavonoid family and widely distributed in the human diet such as beans, fruits, vegetables, and red wines. It has been reported that anthocyanins have positive effects as antioxidants. Cyanidin-3-O-glucoside (C3G), a large part of anthocyanin fractions, has protective effects as a scavenger of active oxygen species in ischemia/reperfusion damage (Tsuda et al., 1999, Amorini et al., 2003). Especially, anthocyanins have been shown to reduce the levels of inflammatory mediators in a lung inflammatory disease model (Rossi et al., 2003). These study results suggested that anthocyanins have protective effects in inflammation and oxidative stress-mediated asthma models.
Asthma is an allergic disease that is strongly associated with an infiltration of inflammatory cells such as mast cells, eosinophils, neutrophils and lymphocytes in lung (Elias et al., 2003). Oxidative stress can be associated with asthma by enhancing the production of cytokines (Crapo and Day, 1999, Crapo, 2003). T-helper cell type 2 (Th2) response is known to be essential for the development and perpetuation of asthma by releasing Th2 cytokines such as interleukin (IL)-4, IL-5 and IL-13. Especially, these cytokines are indicated to play the dominant role in the induction and effector phases of allergic inflammation. IL-13 produced by T cells, eosinophils, mast cells, and basophils is known to have various biological properties associated with asthma and be present at an increased level in asthmatic airways and lungs. IL-13 can induce mucus hypersecretion, airway inflammation, airway hyperresponsiveness, and tissue fibrosis through its receptors (Kips, 2001, Wills-Karp, 2004). Many studies have suggested that the blockade of IL-4, IL-13 or IL-13 signaling pathway may have a therapeutic potential for asthma. Recently, the adaptive response of Th2 cytokines (IL-4 and IL-13) has been reported to significantly decrease synoviocyte and monocyte COX-2 mRNA and protein levels in vitro (Sugiyama et al., 1996, Endo et al., 1996). COX-2 regulation by Th2 cytokines may have considerable functional implications in diseases such as asthma.
In the present study, we examined whether anthocyanins would have protective effects on allergic airway inflammation and AHR through regulation by various cytokines and COX-2 in a mouse model of asthma.
Section snippets
Animals and treatment
Male BALB/c mice (25–31 g, Oriental Co., Ltd. Kyounggi, Korea) were used in this study. The animals were kept in a storage room under the conditions of constant temperature (23 ± 3 °C), relative humidity (50 ± 10%), and illumination (12 h light/dark cycles) until the initiation of the experiment. All animals were fed with standard animal chow daily and had access to drinking water ad libitum. For sensitization, the asthma control group and anthocyanin treated groups received 20 μg of ovalbumin (OVA,
Collection of BAL (bronchoalveolar lavage) fluid and differential cell count
To determine whether anthocyanins could change pulmonary immune responses, inflammatory cell recruitment to the lung in response to anthocyanins (150 or 300 mg/kg) in an OVA sensitized asthma model was compared with non-treated normal group. Differential cell counts indicated that the changes in total cell number were accounted for by an increase in the representation of eosinophils as a proportion of total white blood cells in asthma relative to normal animals. The percentages of eosinophils
Discussion
In this study, we have demonstrated that the intake of anthocyanins effectively suppressed allergic inflammation and AHR in a model of asthma. Furthermore, we found that these effects of anthocyanins were related to decrease of Th2 and pro-inflammatory cytokines. Asthma is a chronic disease that causes bronchoconstriction, inflammation and hyperresponsiveness to cholinergic agonists, such as methacholine (Chung, 1986, Barnes, 1989). Airway inflammation and hyperreactivity in asthma are likely
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These authors contributed equally to this work.