Artesunate alleviates chronic allergic rhinitis and asthma syndrome via the CCR3/NF-κB pathway: a comprehensive...

Chronic allergic rhinitis and asthma syndrome (CARAS) is a comorbid inflammatory condition affecting both upper and lower airways, with limited treatment options. Artesunate (ART), a derivative of artemisinin, has shown anti-inflammatory properties, but its role in CARAS remains unclear.

To explore the therapeutic mechanisms of ART in CARAS using a comprehensive multi-methodological approach, focusing on the CCR3/NF-κB signaling pathway.

A CARAS mouse model was established to evaluate the in vivo effects of ART. Network pharmacology, RNA sequencing, and machine learning were applied to identify key targets and pathways. Molecular docking and molecular dynamics simulations assessed ART-target interactions. Western blotting validated critical signaling changes.

ART treatment alleviated nasal and lung tissue damage, reduced inflammation, and restored epithelial integrity. It significantly lowered serum IgE and Th2-related cytokines (IL-4, IL-5, IL-13). Network pharmacology identified 29 target genes involved in pathways such as Th17 differentiation and NF-κB signaling. Machine learning consistently highlighted STAT3 as a central target. Docking studies showed high binding affinity between ART and STAT3. ART also downregulated CCR3 and inhibited NF-κB activation as confirmed by Western blot.

ART effectively ameliorates CARAS by suppressing inflammation and modulating immune signaling via the CCR3/NF-κB axis. These findings support ART as a potential therapeutic agent for CARAS.