Carpesium abrotanoides extract attenuates chronic obstructive pulmonary disease-associated airway inflammation through inhibition of MAPK signaling

ETHNOPHARMACOLOGICAL RELEVANCE: Carpesium abrotanoides L. (Asteraceae) is traditionally used to treat inflammatory conditions including bronchitis, sore throat, and tonsillitis. However, the evidence supporting its potential in chronic obstructive pulmonary disease (COPD) treatment remains limited. AIM OF THE STUDY: To evaluate the effects of C. abrotanoides extract (CA) in a cigarette smoke extract/lipopolysaccharide (CSE/LPS)-induced mouse model relevant to COPD and to investigate CA's association with modulation of inflammatory mediators and MAPK signaling. MATERIALS AND METHODS: CA was chemically profiled using LC-QTOF MS/MS. Anti-inflammatory activity was assessed in LPS-stimulated RAW 264.7 macrophages by measuring viability, nitric oxide (NO), cytokine release, and MAPK phosphorylation. BALB/c mice exposed to CSE/LPS and received oral CA (25 or 100 mg/kg) or dexamethasone (3 mg/kg). Airway inflammation and lung injury were evaluated via bronchoalveolar lavage fluid (BALF) cell counts and mediator levels, flow cytometry, lung histopathology with semi-quantitative scoring, immunofluorescence (TNF-α, CXCL1, IRAK1), lung MAPK phosphorylation, and qRT-PCR. Antitussive and expectorant properties were evaluated using ammonia-induced cough and phenol red secretion assays, respectively. RESULTS: Ten major constituents of CA were identified. In macrophages, CA reduced LPS-induced NO, pro-inflammatory mediators, and MAPK phosphorylation. In CSE/LPS-exposed mice, CA decreased BALF cellularity, neutrophil infiltration, and inflammatory mediator levels; improved lung histopathology; reduced TNF-α/CXCL1/IRAK1 signal; and inhibited inflammatory and mucus/remodeling-related genes, including TRPA1. CA also reduced cough frequency and increased phenol red secretion. CONCLUSION: CA attenuated airway inflammation and lung injury in a preclinical model relevant to COPD, with effects consistent with modulation of IRAK1-related signaling and reduced MAPK activation. Further studies in chronic models are warranted.