Wuhu Decoction Alleviates Airway Inflammation via Regulating miRNA-155 and T-bet/GATA3 in Asthmatic Rats

Introduction: Asthma is characterized by chronic airway inflammation and Th1/Th2 immune imbalance. Wuhu decoction (WHD), a classic formulation in Traditional Chinese Medicine, has demonstrated significant clinical efficacy in managing asthmatic exacerbations. However, the precise molecular mechanisms by which WHD ameliorates airway inflammation in asthma remain inadequately characterized. This work was undertaken to assess the protective actions of WHD in alleviating airway inflammation in asthmatic rats and to explore potential mechanisms.

Methods: A total of Eighty female SD rats were used. Twenty rats served as unsensitized controls, and sixty were sensitized with Al(OH)3 and ovalbumin (OVA) to induce asthma. After successful modeling, they were randomly classified into control, model, dexamethasone, and low, medium, and high-dose WHD groups and received corresponding drug intervention for two weeks. Airway reactivity was recorded using plethysmography; lung tissue histological changes were assessed by PAS, H&E, and Masson staining; Gamma-interferon (IFN-γ), interleukin-4 (IL-4), and immunoglobulin E (IgE) serum levels were determined by ELISA; qRT-PCR was used to detect miR-155 in rat lung tissues; Western blot determined GATA3 and T-bet proteins levels in lung tissues of rats; Pearson correlation evaluated correlation between miRNA-155 levels in lung tissues of asthmatic rats and T-bet, GATA3.

Results: The results of airway reactivity indicated successful replication of the asthma rat model. The airway reactivity index in model rats increased significantly by 115.3%, accompanied by elevated inflammatory cells around the trachea and bronchi, excessive proliferation of epithelial cells, and widespread deposition of airway collagen when compared to controls. Serum IL-4 and IgE levels were elevated by 172.7% and 69.2%, while IFN-γ expression was reduced by 38.8%, and miR-155 expression in lung tissue was increased by 187.8% in model rats compared to controls. T-bet expression decreased, while GATA3 expression increased significantly in lung tissues from asthma rats compared to controls. Compared to model rats, both WHD and dexamethasone treatment significantly reduced the airway hyperresponsiveness in rats, alleviated lung tissue damage, reduced epithelial cell proliferation and airway collagen deposition, decreased serum IgE and IL-4 levels, elevated IFN-γ levels, and simultaneously reduced miR-155 expression, GATA3 protein level, and increased T-bet protein level in lung tissues. The miRNA-155 in asthmatic rat lung tissues was negatively correlated with T-bet (r = - 0.1441; P < 0.001), and positively correlated with GATA3 (r = 0.04578; P < 0.0001).

Discussion: This study demonstrates that WHD exerts protective effects against allergic airway inflammation in asthmatic rats by modulating immune responses. WHD treatment significantly attenuated airway hyperresponsiveness, reduced epithelial cell proliferation, mucus secretion, and collagen deposition. The inverse correlation between miR-155 and T-bet, along with the positive association with GATA3, suggests that WHD may alleviate asthma through miR-155/T-bet/GATA3 axis. These findings highlight WHD as a promising traditional therapy with potential molecular targets for future asthma interventions.

Conclusion: WHD effectively alleviated airway inflammation in asthmatic rats, and the protective effects were associated with inhibiting miR-155 levels in lung tissue, regulating T-bet/GATA3 imbalance, and reducing the secretion of inflammatory factors IL-4 and IgE.