Mechanism of Ellagic Acid in Ameliorating Bleomycin-induced Lung Injury
10.11714/jsysu.med.YX20260027
- VernacularTitle:鞣花酸改善博来霉素诱导肺损伤的机制
- Author:
Li SHAO
1
;
Ke TAO
2
;
Li WEI
1
;
Juanli LI
3
;
Zhizhi SHI
1
;
Shugui QIAO
4
;
Shaokang WANG
1
Author Information
1. Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region ，School of Medicine， Xizang Minzu University， Xianyang 712082， China
2. Key Laboratory of Environmental Medicine and Engineering of Ministry of Education， Department of Nutrition and Food Hygiene， School of Public Health， Southeast University， Nanjing 210009， China
3. The First Affiliated Hospital of Xi'an Jiaotong University， Xi’an 710061， China
4. The Hospital of Fengxian，Baoji 721700， China
- Publication Type:Journal Article
- Keywords:
pulmonary fibrosis;
ellagic acid;
bleomycin;
interleukin-17;
signaling pathway
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2026;47(3):496-508
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the protective effect of ellagic acid （EA） against bleomycin （BLM）-induced pulmonary fibrosis and associated pulmonary function impairment in mice， and to elucidate its relationship with the regulation of the interleukin（IL）-17/ nuclear factor （NF）-κB/ matrix metalloproteinase （MMP）9 signaling axis. MethodsA pulmonary fibrosis model was established in male C57BL/6J mice via intratracheal BLM injection. Interventions included IL-17 neutralizing antibody， Ixekizumab， SB-3CT， PDTC， or EA were used to modulate the IL-17/NF-κB/MMP9 signaling axis. Pathological changes in lung tissue were observed via HE， Masson， and Sirius red staining. Pulmonary function was assessed using a pulmonary function test （PFT）. Western blot and qRT-PCR were employed to detect related protein and gene expression. Network pharmacology was utilized to predict the potential targets of EA. A protein-protein interaction （PPI） network was constructed using the STRING database and Cytoscape. Molecular docking was performed to validate the binding capability of EA to core targets. ResultsBLM successfully induced obvious pulmonary fibrosis and lung dysfunction in mice， significantly elevating the level of the pro-inflammatory cytokine IL-17. This was associated with the activation of the transcription factor NF-κB p65， leading to the upregulation of the pro-fibrotic factor MMP9. Inhibition of the IL-17/NF-κB/MMP9 signaling axis markedly alleviated the degree of pulmonary fibrosis. EA intervention significantly suppressed the BLM-induced increase in IL-17， blocked the activation of the NF-κB/MMP9 pathway， and consequently reduced lung fibrotic lesions and improved pulmonary function. ConclusionEA may effectively ameliorate BLM-induced pulmonary fibrosis and lung dysfunction in mice， likely by inhibiting the inflammatory and fibrotic responses mediated through the IL-17/NF-κB/MMP9 signaling pathway.
