Lifei Qingchang Granules alleviate airway inflammation in a mouse model of bronchiectasis by inhibiting neutrophil extracellular traps.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Lifei Qingchang Granules (LFQC) is a traditional Chinese medicine formula used to treat acute exacerbations and prevent recurrence of bronchiectasis. Excessive neutrophil extracellular trap (NET) formation has been increasingly recognized as a key driver of airway inflammation and tissue injury in bronchiectasis. However, the mechanism by which LFQC modulates NET dynamics remains unclear. AIM OF STUDY: To evaluate the therapeutic efficacy and mechanism of LFQC in bronchiectasis, focusing on NET regulation. MATERIALS AND METHODS: A recurrent Pseudomonas aeruginosa-induced mouse model of bronchiectasis was established and treated with LFQC. Airway inflammation and dilation were assessed by micro-CT, histology, and ELISA. In vivo and in vitro assays examined NET formation and oxidative stress, while LC-MS, network pharmacology, and molecular docking were applied to identify active compounds and their potential targets. RESULTS: LFQC significantly reduced bacterial burden, airway dilation, and inflammatory infiltration in bronchiectasis mice. Levels of IL-1β, IL-6, TNF-α, MPO, and NE in bronchoalveolar lavage fluid were decreased. LFQC suppressed pulmonary NET formation and reduced Cit-H3, MPO, and NE expression. In vitro, LFQC-containing serum inhibited LPS-induced NETosis and ROS production by down-regulating the NOX2-p47 phox complex. Molecular docking revealed strong binding between LFQC components and NOX2/p47 phox. CONCLUSION: LFQC alleviates airway inflammation in bronchiectasis by inhibiting NET formation through the NOX2-p47 phox/ROS pathway, supporting its potential as a therapeutic agent for bronchiectasis.