Salidroside and Hongjingtian Injection Inhibit the Onset and Progression of Asthma via Pyroptosis in the Ozone‐Exposed Inflammation Environment

BACKGROUND: Ozone is a common air pollutant, and exposure to high concentrations of ozone can promote the onset and progression of asthma. Pyroptosis is a form of cell death associated with asthma exacerbation. METHODS: This study aimed to identify ozone-related pyroptosis genes through network toxicology and RNA-seq analysis and to investigate the role of pyroptosis genes in asthma using multiple asthma tissue samples and machine learning methods. Key pyroptosis genes with significant roles in asthma were identified through experiments and multiomics approaches. Using network pharmacology methods, we screened traditional Chinese medicine (TCM) components associated with key pyroptosis genes. Through molecular clustering and molecular docking, we explored the interaction between TCM components and key genes. Using animal model drug interventions, we further analyzed the therapeutic effects of TCM components targeting pyroptosis on asthma under ozone exposure. RESULTS: This study identified 16 ozone-related pyroptosis genes through network pharmacology and transcriptomics data analysis. Based on multiple asthma tissue samples and machine learning methods, the 16 pyroptosis genes were found to have diagnostic predictive roles in asthma. Through experimentation and multiomics approaches, gasdermin D (GSDMD) was identified as a key gene in exacerbating asthma under ozone exposure. Furthermore, scRNA-seq and virtual knockout revealed that GSDMD exerts a pro-inflammatory effect on the asthma microenvironment. Using network pharmacology methods, we screened for salidroside, a Chinese herbal component related to GSDMD. Through molecular clustering and molecular docking, we identified seven salidroside analogs in Hongjingtian injection (HJT). Using an animal model drug intervention, we further analyzed the intervention effects of salidroside and HJT on asthma under ozone exposure. CONCLUSIONS: Ozone promotes the onset and progression of asthma by exacerbating inflammation and pyroptosis. salidroside and its analogs can target GSDMD to inhibit asthma exacerbation in ozone-induced inflammation environments.