Work

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

Year: 2025

Type: article

Abstract: 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.

Source: International Immunopharmacology

DOI: 10.1016/j.intimp.2025.115003