Abstract
Allergic asthma has been considered as a respiratory disorder with pathological features of airway inflammation and remodeling, which involves oxidative stress. Formononetin (FMT) is a bioactive isoflavone obtained from Chinese herb Radix Astragali, and has been reported to have notable anti-inflammatory and antioxidant effects in several diseases. The purpose of our study was to elaborate the effects of FMT on asthma and the underlying mechanisms. To establish allergic asthma model, BALB/c mice were given ovalbumin (OVA) sensitization and challenge, treated with FMT (10, 20, 40 mg/kg) or dexamethasone (2 mg/kg). The effects of FMT on lung inflammation and oxidative stress were assessed. In OVA-induced asthmatic mice, FMT treatments significantly ameliorated lung function, alleviated lung inflammation including infiltration of inflammatory cells, the elevated levels of interleukin (IL)-4, IL-5, and IL-13, immunoglobulin (Ig) E, C-C motif chemokine ligand 5 (CCL5, also known as RANTES), CCL11 (also called Eotaxin-1), and IL-17A. In addition, FMT treatments eminently blunted goblet cell hyperplasia and collagen deposition, and remarkably reduced oxidative stress as displayed by decreased reactive oxygen species (ROS), and increased superoxide diamutase (SOD) activity. Furthermore, to clarify the potential mechanisms responsible for the effects, we determined the inflammation and oxidation-related signaling pathway including nuclear factor kappa β (NF-κB), c-Jun N-terminal kinase (JNK), and the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). FMT treatments appeared to dramatically inhibit the activation of NF-κB and JNK, significantly elevated the expression of heme oxygenase 1 (HO-1) but failed to activate expression of Nrf2. In conclusion, our study suggested that FMT had the therapeutic effects in attenuating airway inflammation and oxidative stress in asthma.
Highlights
Asthma is a chronic respiratory disorder of the conducting airways where the epithelial barrier working together with the adaptive and innate immune cells respond to a diverse range of exogenous inhaled stimuli such as allergens and air pollutants (Holgate, 2011)
Asthma group showed a dose-dependent decline in Cydn (Figure 2B) and an increase in RL at Mch dose of 6.25 (p = 0.068) and 12.5 mg/ml (p < 0.001) (Figure 2A) compared with normal control group, which revealed that mice exposed to OVA have developed significant
FMT exhibited a significant increment in Cydn especially in the asthma +FMT 40 mg/kg group, which was able to gradually normalize Cydn responding to Mch of 6.25 and 12.5 mg/ml (p < 0.05) (Figures 2B, D)
Summary
Asthma is a chronic respiratory disorder of the conducting airways where the epithelial barrier working together with the adaptive and innate immune cells respond to a diverse range of exogenous inhaled stimuli such as allergens and air pollutants (Holgate, 2011). Inhaled corticosteroids (ICS) and long-acting b2-agonist (LABA) are known as the most common pharmacological options for management of asthma. These medications can attenuate airway inflammation and relieve respiratory symptoms, some asthmatic patients respond poorly to corticosteroid-based therapies, and even experience the severe adverse effects (Williams et al, 2004; Aalbers et al, 2016). Alternative therapeutic options designed to alleviate airway inflammation and remodeling (such as herbal medicines which has long been used for treatment of bronchial asthma) are urgently required and expected to have better efficacy and safety in asthma therapy
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