Dihydroartemisinin alleviates allergic airway inflammation by suppressing the PI3K-AKT signaling axis: integrated network pharmacology and experimental validation.
8 affiliations
- 1The First Dongguan Affiliated Hospital, College of Medical Technology, Guangdong Medical University, Dongguan, 523808, China. [email protected].
- 2Dongguan Key Laboratory of Immune Regulation and Prevention of Pulmonary Diseases, Liaobu Hospital of Dongguan City, Dongguan, 523430, China. [email protected].
- 3Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, Guangdong Medical University, Dongguan, 523808, China. [email protected].
- 4The First Dongguan Affiliated Hospital, College of Medical Technology, Guangdong Medical University, Dongguan, 523808, China.
- 5Dongguan Key Laboratory of Immune Regulation and Prevention of Pulmonary Diseases, Liaobu Hospital of Dongguan City, Dongguan, 523430, China.
- 6Dongguan Key Laboratory of Immune Regulation and Prevention of Pulmonary Diseases, Liaobu Hospital of Dongguan City, Dongguan, 523430, China. [email protected].
- 7Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, Guangdong Medical University, Dongguan, 523808, China. [email protected].
- 8The First Dongguan Affiliated Hospital, College of Medical Technology, Guangdong Medical University, Dongguan, 523808, China. [email protected].
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.
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BibTeX
@article{ouyang2026dihydroartemisinin,
title = {{Dihydroartemisinin alleviates allergic airway inflammation by suppressing the PI3K-AKT signaling axis: integrated network pharmacology and experimental validation.}},
author = {Suidong Ouyang and Daichi Chen and Hangyu Li and Jingyi Deng and Yuqia Xie and Su Chen and Xinlong Lian and Gonghua Huang and Xueqin Huang},
journal = {Respiratory research},
year = {2026},
month = oct,
doi = {10.1186/s12931-026-03956-0},
url = {https://europepmc.org/article/MED/42963570},
note = {CC BY},
}
RIS
TY - JOUR
TI - Dihydroartemisinin alleviates allergic airway inflammation by suppressing the PI3K-AKT signaling axis: integrated network pharmacology and experimental validation.
AU - Suidong Ouyang
AU - Daichi Chen
AU - Hangyu Li
AU - Jingyi Deng
AU - Yuqia Xie
AU - Su Chen
AU - Xinlong Lian
AU - Gonghua Huang
AU - Xueqin Huang
PY - 2026
DA - 2026/10/15
JO - Respiratory research
DO - 10.1186/s12931-026-03956-0
UR - https://europepmc.org/article/MED/42963570
AB - 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.
SN - 1465-9921
SN - 1465-993X
ER -