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

Youwei Bao,* Zhiqiang Zhang,* Binbin Shi, Qi Chen, Ying Zhang, Xinhua Zhu Department of Otorhinolaryngology Head and Neck Surgery, The second Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinhua Zhu, Department of Otorhinolaryngology Head and Neck Surgery, The second Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China, Email [email protected]: 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.Keywords: allergic rhinitis, cGAS-STING, mitochondrial damage