Rosavin Alleviates COPD Pathology by Inhibiting IL-17-Enriched NET Formation and NF-κB Signaling in Rats

Chronic obstructive pulmonary disease (COPD) is a leading cause of death, characterized by persistent inflammation, microbiota dysbiosis, and excessive neutrophil extracellular trap (NET) formation. Current treatments often fall short in fully addressing the complex inflammatory cascade, particularly the persistent activation of pathways like nuclear factor-kappa B (NF-κB). Rosavin, a natural phenylpropanoid glycoside, is known for its anti-inflammatory and immunomodulatory properties, making it a candidate for exploring novel therapeutic strategies in COPD.

A COPD rat model was established via intratracheal lipopolysaccharide instillation combined with chronic passive cigarette smoke exposure. Rats were treated with Rosavin (50 or 100 mg/kg) or the NF-κB inhibitor BAY 11-7082 (3 mg/kg). Pulmonary function tests (FEV1/FVC, PEF, airway resistance), histopathological evaluation (HE, PAS staining), and BALF inflammatory cell counts were performed. ELISA assessed cytokine levels, while oxidative stress markers (MDA, MPO, SOD) were measured. NET formation was quantified using MPO-DNA ELISA, Western blotting, and immunofluorescence for CitH3 and MPO/IL-17 colocalization. Lung microbiota composition was analyzed by 16S rRNA gene sequencing. CSE-stimulated BEAS-2B cells were used for in vitro NF-κB activation studies.

Rosavin treatment significantly inhibited NF-κB activation, leading to improved lung function and reduced structural damage in COPD rats. It also reduced oxidative stress markers and inflammatory cytokines. A key finding was Rosavin's suppression of NET formation, including IL-17-enriched NETs, by downregulating MPO, NE, and CitH3. In CSE-stimulated BEAS-2B cells, Rosavin similarly reduced NF-κB activation and cytokine release. Microbiota profiling revealed that Rosavin restored beneficial taxa, such as Lactobacillus spp., which were decreased in COPD rats, while reducing the enrichment of Fusobacterium nucleatum. The NF-κB inhibitor BAY 11-7082 produced comparable effects, strongly supporting NF-κB inhibition as a central mechanism. > Rosavin significantly inhibited NF-κB activation, improved lung function, and reduced structural damage, oxidative stress, and inflammatory cytokines in COPD rats.