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Updated: Oct 17, 2025
Oropharyngeal Administration of Bleomycin in the Murine Model of Pulmonary Fibrosis
Published on: May 9, 2025
Mefunidone Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Mice
Yuanyuan Han1,2,3, Mao Jiang1,2, Rongling He1,2
1Department of Pulmonary and Critical Care Medicine, The Third Xiangya Hospital of Central South University, Changsha, China.
Abstract:
Idiopathic pulmonary fibrosis (IPF) is one of the most common and devastating interstitial lung diseases with poor prognosis. Currently, few effective drugs are available for IPF. Hence, we sought to explore the role of mefunidone (MFD), a newly synthesized drug developed by our team, in lung fibrosis. In this study, MFD was found to attenuate bleomycin (BLM) -induced lung fibrosis and inflammation in mice according to Ashcroft and alveolitis scoring. The protein contents and total cell counts in bronchoalveolar lavage fluids of BLM-treated mice were also lowered by MFD. Moreover, the elevation of TGF-β/Smad2 and phosphorylation of MAPK pathways was repressed by MFD. Additionally, MFD attenuated the swelling and vacuolization of mitochondria, lowered the ratio of apoptotic cells, restored the mitochondrial membrane potential, and reversed the expression of cleaved-caspase 3, Bcl-2 and Bax. Meanwhile, the level of epithelial marker, E-cadherin, was restored by MFD, while the levels of mesenchymal markers such as Snail and vimentin were down-regulated by MFD. Besides, MFD inhibited the expression of fibronectin and α-smooth muscle actin in TGF-β treated normal human lung fibroblasts. Thus, our findings suggested that MFD could ameliorate lung fibrosis, cell apoptosis and EMT potentially via suppression of TGF-β/Smad2 and MAPK pathways.
Insights
Mefunidone (MFD) effectively reduces lung fibrosis and inflammation in mice by inhibiting key fibrotic pathways. This new drug candidate shows promise in treating idiopathic pulmonary fibrosis (IPF) and related conditions.
Area of Science:
- Pulmonology
- Pharmacology
- Cell Biology
Background:
- Idiopathic pulmonary fibrosis (IPF) is a severe interstitial lung disease with limited treatment options.
- Developing novel therapeutic agents for IPF is a critical unmet medical need.
Purpose of the Study:
- To investigate the anti-fibrotic effects of mefunidone (MFD), a novel drug synthesized by the research team.
- To elucidate the underlying molecular mechanisms of MFD in ameliorating lung fibrosis.
Main Methods:
- Bleomycin (BLM)-induced lung fibrosis mouse model and TGF-β-treated human lung fibroblasts were used.
- Histological scoring (Ashcroft, alveolitis), bronchoalveolar lavage fluid analysis, and Western blotting were performed.
- Mitochondrial function, apoptosis markers, and epithelial-mesenchymal transition (EMT) markers were assessed.
Main Results:
- MFD significantly attenuated BLM-induced lung fibrosis and inflammation.
- MFD reduced protein and cell counts in bronchoalveolar lavage fluid.
- MFD inhibited TGF-β/Smad2 and MAPK signaling pathways, reduced mitochondrial damage and apoptosis, and reversed EMT.
- MFD decreased fibronectin and α-smooth muscle actin expression in fibroblasts.
Conclusions:
- Mefunidone demonstrates significant potential in ameliorating lung fibrosis, cell apoptosis, and EMT.
- MFD exerts its therapeutic effects possibly through the suppression of TGF-β/Smad2 and MAPK pathways.
- MFD represents a promising therapeutic candidate for idiopathic pulmonary fibrosis.
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