Yu-Ping-Feng-San mitigates development of emphysema and its exacerbation induced by influenza virus in mice

Abstract

ObjectiveYu-Ping-Feng-San (YPFS) has been found to significantly reduce exacerbation rate and the risk of a second exacerbation in patients with chronic obstructive pulmonary disease (COPD). However, the effect of YPFS on emphysema development and its exacerbation caused by influenza virus is still unclear. This study aims to investigate the protective effect of YPFS on the impaired lung function and increased inflammation that occurs during the development and exacerbation of emphysema. MethodsWe developed an emphysema mice model using porcine pancreatic elastase (PPE) and treated it with YPFS [1 950, 975, and 487.5 mg/(kg·d)] once daily. On day 7 post-PPE challenge, peripheral leucocytes and inflammatory cells in lungs were analyzed, respectively. Pulmonary inflammatory mediators were determined. On day 28, invasive lung function and inflammatory mediators were measured. In addition, histopathological changes at both time points were assessed. We also developed an exacerbation of emphysema mouse model by intratracheally infected mice with influenza H1N1 virus on day 28. After infection, YPFS administration was discontinued, and the protective effect was determined by lung function, viral titer and cytokine levels in the lungs, and lung histopathological changes on day 5 post-infection. ResultsThe results demonstrated that 32 days of YPFS administration significantly improved lung function and reduced severity of emphysema in PPE-treated mice. It significantly reduced monocytes and neutrophils, while increased lymphocytes in peripheral blood. Additionally, YPFS inhibited the accumulation of alveolar macrophages and the expression of cytokines in mice treated with PPE. MMP-9, fibronectin, and VEGF, which are inflammatory mediators associated with airway remodeling, were also inhibited by YPFS. The results also demonstrated that YPFS prophylaxis prior to viral infection benefited mice treated with PPE and H1N1 as evidenced by decreased lung cytokine levels, lowered lung index, and improved lung histopathology. ConclusionYPFS prevents the development of emphysema and its exacerbation induced by influenza virus in mice. Our finding provides scientific evidence for the prophylaxis application of YPFS in mitigating acute exacerbation of chronic obstructive pulmonary disease (AECOPD).