Demethyleneberberine ameliorates pulmonary fibrosis by inhibiting the NLRP3 inflammasome and the epithelial-mesenchymal transition.

BACKGROUND AND AIMS

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by inflammation and fibrosis. Demethyleneberberine (DMB), a natural compound derived from traditional Chinese medicine, possesses both anti-inflammatory and antifibrotic properties. This study investigated the therapeutic potential of DMB in pulmonary fibrosis and elucidated its underlying mechanisms of action.

MATERIALS AND METHODS

Pulmonary fibrosis was induced in male C57BL/6 mice via intratracheal administration of bleomycin (BLM, 1.5 mg/kg). The mice were randomly assigned to four groups (n = 10 per group): control, BLM, BLM + DMB (5 mg/kg), and BLM + DMB (10 mg/kg). An in vitro model of pulmonary fibrosis was established by stimulating MLE-12 cells with transforming growth factor-β1 (TGF-β1, 5 ng/mL). Lung structural and functional changes were assessed using hematoxylin and eosin staining, lung-function testing, and micro-computed tomography. The relationship between NLRP3 and EMT during the process of DMB alleviating pulmonary fibrosis was further explored by inducing NLRP3 overexpression in vitro.

RESULTS

DMB treatment significantly alleviated histopathological alterations and reduced collagen deposition in lung tissues. It also inhibited activation of both the canonical and non-canonical NLRP3 inflammasomes. DMB reversed EMT-related marker expression in both in vivo and in vitro models. Notably, overexpression of NLRP3 in vitro partially abrogated the suppressive effect of DMB on the EMT.

CONCLUSION

DMB ameliorates pulmonary fibrosis by inhibiting NLRP3 inflammasome activation and suppressing the EMT. Inhibition of NLRP3 appears to play a critical role in mediating the antifibrotic effects of DMB. These findings imply that DMB may represent a promising therapeutic candidate for clinical management of IPF.