Safranal restores RUNX3-mediated immunoregulation by inhibiting the NLRP3 inflammasome in allergic asthma

Safranal is an active ingredient with pharmacological anti-inflammatory effects derived from Crocus sativus essential oil. To explore the comprehensive effects of Safranal on airway inflammation, airway hyperreactivity, and remodeling and its potential mechanisms through the allergic asthma model, an in vitro model of ASMC cells stimulated by TNF-α was established. The cells were transfected with si-RUNX3 and RUNX3 overexpression plasmids, and DEX was used as a positive control. The expression of RUNX3 was detected by western blot and immunofluorescence. The levels of inflammatory factors were measured by ELISA, while flow cytometry detected the anti-apoptotic effects and ROS production. Subsequently, OVA-sensitized WT mice and RUNX3-KO mice were administered with DEX and Safranal for 2 weeks to establish a mouse model of allergic asthma, and changes in airway hyperresponsiveness, inflammatory manifestations, and airway remodeling were detected. The mechanism of Safranal was verified by detecting the expression of RUNX3, inflammation, and fibrosis-related proteins in the lung tissues. By modulating the NLRP3/Caspase-1 pathway, Safranal significantly alleviated the negative effects caused by RUNX3 suppression in vivo and in vitro. We propose that Safranal is a potential active compound for the treatment of asthma, and its clinical application value in allergic asthma should be further explored.