Fritillaria thunbergii Miq. Extract ameliorated experimental pulmonary fibrosis partly through the PI3K/AKT/FOXO signalling pathway

Abstract

Ethnopharmacological relevance

Pulmonary fibrosis is an irreversible lung disease with a high mortality rate. Zhebeimu (ZBM, Fritillaria thunbergii Miq.) is a Chinese medicine commonly used for the treatment of pulmonary fibrosis in China.

Aim of the study

In this study, the protective effect and mechanism of ZBM extract in the treatment of pulmonary fibrosis were investigated in vivo and in vitro.

Materials and methods

The protective effect of ZBM extract was assessed using an in vivo model of bleomycin (BLM) tracheal drip and transforming growth factor-β(TGF-β1)-induced fibroblasts to simulate pulmonary fibrosis, and lung function, lung histopathological status and hydroxyproline were tested. Relevant pathways were detected using protein blotting, immunofluorescence and immunohistochemistry.

Results

ZBM extract effectively improved lung function, inflammatory changes and fibrotic deposition in the lungs, and reduced the expression of fibroblast markers in mice. In addition, ZBM extract significantly inhibited TGF-β1-induced hyperphosphorylation of FOXO3, and simultaneously improved the low expression level of FOXO3 prototype protein and significantly reduced the phosphorylation level of PI3K-p85 and AKT1, suggesting that ZBM extract improves lung fibrosis by inhibiting the over-activation of PI3K/AKT/FOXO signalling pathway.

Conclusion

The PI3K/AKT/FOXO signalling pathway is critical for ZBM extract to improve pulmonary fibrosis.