Therapeutic effects of Lianhua Qingke on COPD and influenza virus-induced exacerbation of COPD are associated with the inhibition of NF-κB signaling and NLRP3 inflammasome responses

•LHQK can mitigate chronic pulmonary inflammation and structural damage, which are hallmarks of COPD progression.•LHQK also exhibits promising antiviral properties and immunomodulatory effects in H1N1-induced AECOPD models.•LHQK’s immunomodulatory effects is associated with the inhibition of NF-κB signaling and NLRP3 inflammasome responses.•LHQK could be a valuable therapeutic option for preventing and treating AECOPD in clinical settings. Lianhua Qingke (LHQK), a traditional Chinese medicine (TCM) used clinically for the treatment of respiratory diseases with acute tracheobronchitis, and cough, has demonstrated promising efficacy in suppressing inflammation, inhibitingmucin secretion, reducing goblet cell hyperplasia andmaintainingairway epithelial integrity. However, its efficacy in managing chronic obstructive pulmonary disease (COPD) progression, particularly virus-induced acute exacerbations of COPD (AECOPD),remains unclear. Here, cigarette smoke (CS)-induced COPD and CS+virus (influenza H1N1)-triggered AECOPD mouse models were employed to evaluated the therapeutic potential of LHQK. The findings demonstrated that LHQK treatment led to significant improved pulmonary function, suppressed pulmonary inflammation, alleviated lung histopathological changes, and preserved airway epithelial integrity in COPD mice. Additionally, LHQK treatment effectively inhibited viral replication in the lungs of AECOPD mice and decreased recruitment of immune cells (M1 macrophages, progenitor-exhausted T cells and CD8 + T cells) to the lungs. Western blot analysis indicated that the therapeutic effects of LHQK are associated with the inhibition ofNF-κB signaling and NLRP3 inflammasome activation. Collectively, these findings elucidate the underlying mechanisms by which LHQK mitigates COPD and AECOPD, thereby supporting its potential as a therapeutic option for individuals afflicted with these conditions.