Fudosteine attenuates lung inflammation in mice with PM2.5-induced asthma exacerbation by inhibiting pyroptosis via the NLRP3/caspase-1/GSDMD pathway

This study aimed to explore the potential preventive effects of fudosteine (Fud) on PM2.5-induced asthma exacerbations in a murine model. BALB/c mice were randomly allocated into six groups: control, Fud, ovalbumin (OVA), OVA+Fud, OVA+PM2.5, and OVA+PM2.5 + Fud. An asthma model was established through OVA sensitization and challenge. Compared to the OVA group, PM2.5 exposure exacerbated allergic asthma, as evidenced by increased collagen fiber deposition, goblet cell metaplasia, mucus secretion, heightened airway inflammation, elevated total cell and eosinophil counts, and upregulated levels of interleukin (IL)-1β, IL-18, and NLRP3 expression in lung tissues. Notably, fudosteine treatment mitigated these pathological changes. Western blot analysis revealed that fudosteine significantly reduced the expression of NLRP3, caspase-1, gasdermin D (GSDMD), cleaved-caspase-1, and cleaved-GSDMD in lung tissues. In conclusion, fudosteine alleviated lung inflammation, collagen deposition, and mucus secretion in PM2.5-induced asthma exacerbation, potentially by inhibiting the NLRP3 inflammasome-mediated pyroptosis pathway.