Mucus is an important gel-forming protective layer in the respiratory tract that mainly consists of mucins, among which MUC5AC and MUC5B are extremely important, with MUC5B playing an important defense role and MUC5AC being secreted in large quantities during respiratory illnesses, which results in the formation of sputum and increased health problems [1,2]. Past studies have shown that high MUC5AC expression in the lungs is significantly increased in diseases such as chronic obstructive pulmonary disease (COPD) and allergic asthma [[3], [4], [5], [6]], which can aggravate airway resistance, leading to dyspnea and even exacerbation of the condition.

COPD, a chronic respiratory disease, is characterized by tracheal obstruction, airway destruction, disruption of alveolar attachments, and lung damage [7]. COPD has become a global health disease and the third leading cause of death worldwide [8]. The pathogenesis of COPD is mainly due to a series of inflammatory responses triggered by the entry of harmful particles into the airways, and smoking is considered to be the most critical causative factor of COPD [9]. The pathogenesis of COPD has not been fully elucidated by modern pharmacologic studies, but it involves several major factors, including the inflammatory response, oxidative stress, and mucus hypersecretion [8].

Inula japonica Thunb. is a plant of the genus Inula in the Asteraceae family and is mainly used in traditional Chinese medicine to treat inflammation, coughs and phlegm. In recent years, several studies have shown that I. japonica can be used to treat lung diseases, including lung injury and pulmonary fibrosis [[10], [11], [12]], suggesting that I. japonica might contain active ingredients for the treatment of lung diseases. 1-O-Acetylbritannilactone is a major component of I. japonica [13] and has a wide range of medicinal activities [14,15]. Therefore, in the search for effective anti-inflammatory and expectorant drug candidates, ABL has attracted our attention.

In our study, we explored the anti-inflammatory and anti-MUC5AC activities of ABL in RAW264.7 cells and NCI-H292 cells, respectively, investigated the targets and potential mechanisms via network pharmacology, CETSA, MST and Western blotting, and examined the efficacy of ABL in vivo via a COPD mouse model and the phenol red test.