Study on the Mechanism of Artesunate in Modulating AR Epithelial Injury and Th2-Type Inflammatory Status.

Abstract

Objective: To evaluate the therapeutic efficacy of Artesunate (ART) in a mouse model of allergic rhinitis (AR) induced by house dust mite (HDM) and explore its underlying mechanism.

Experimental methods: Transcriptome sequencing (RNA-seq) analysis identified differentially expressed genes (DEGs) in nasal mucosa between healthy and allergic mice, with Gene Set Enrichment Analysis (GSEA) revealing STING pathway activation. We established a house dust mite (HDM)-induced allergic rhinitis (AR) mouse model via intraperitoneal sensitization. Artesunate (ART) efficacy was evaluated through dose-response testing (10-30 mg/kg), with 30 mg/kg identified as the optimal therapeutic dose. Mice were stratified into four groups: normal control (NC), NC+ART, AR model, and AR+ART-treated. Interventions were administered intraperitoneally, followed by systematic evaluation of: ① behavioral symptoms (sneezing/nasal scratching), ② histopathological changes in nasal and lung tissues, ③ serum TH2 cytokine levels, and ④ nasal mucosal protein expression profiles.

Results: With increasing concentrations of Artesunate (10, 20, 30 mg/kg), there was a significant improvement in the TH2 inflammatory status in AR mice. The cGAS-STING signaling pathway determines the degree of epithelial tissue inflammatory damage and systemic TH2-type inflammatory status in AR mice. Artesunate inhibits the cGAS-STING signaling pathway, protects the mitochondrial structure of epithelial tissue in AR mice, and improves epithelial damage and systemic TH2-type inflammatory status.

Conclusion: This study presents a new treatment approach for respiratory allergies by clarifying how Artesunate (ART) alleviates allergic rhinitis, identifying effective dosage ranges, and demonstrating its potential for developing ART- and cGAS-STING-targeted therapies, ultimately advancing clinical translation.