Work

Dihydroartemisinin alleviates allergic airway inflammation by suppressing the PI3K-AKT signaling axis: integrated network pharmacology and experimental validation

Year: 2026

Type: article

Abstract: BACKGROUND: Allergic asthma is a heterogeneous inflammatory airway disorder driven by dysregulated immune responses and epithelial-immune crosstalk. Dihydroartemisinin (DHA), an active derivative of artemisinin, exhibits broad anti-inflammatory and immunomodulatory properties; however, its mechanistic role in allergic asthma remains incompletely defined. METHODS: Network pharmacology was employed to predict potential therapeutic targets and signaling pathways of DHA in asthma. These predictions were validated in a house dust mite (HDM) induced murine asthma model and HDM stimulated human bronchial epithelial (HBE) cells using histopathology, flow cytometry, RT-qPCR, Western blotting, ELISA, and molecular docking. RESULTS: Network analysis identified nine hub targets and highlighted the PI3K-AKT pathway as a central regulatory axis. In vivo, DHA markedly attenuated airway inflammation, reduced eosinophil and neutrophil infiltration, and decreased Th2 cytokine production. In HDM-stimulated HBE cells, DHA suppressed pro-inflammatory cytokine expression and downregulated EGFR, MMP9, and PTGS2. Mechanistically, DHA inhibited activation of the PI3K-AKT-mTOR signaling cascade both in vitro and in vivo, consistent with molecular docking predictions demonstrating stable binding of DHA to PI3K related targets. CONCLUSIONS: DHA alleviates allergic airway inflammation predominantly through suppression of the PI3K-AKT signaling axis, thereby modulating epithelial inflammatory responses and type 2 immunity. These findings provide mechanistic insight into DHA-mediated immunoregulation and support its potential repositioning as a therapeutic candidate for allergic asthma.

Source: Respiratory Research

DOI: 10.1186/s12931-026-03956-0