Natural product mogrol attenuates bleomycin-induced pulmonary fibrosis development through promoting AMPK activation

Abstract

Pulmonary fibrosis is a chronic and aggresitive interstitial lung disease. We evaluated the anti-fibrotic effect of mogrol isolated from Siratia grosvenorii against pulmonary fibrosis and the underlying mechanism. In vitro, mogrol (10 µM) show anti-fibrotic effects by suppressing TGF-β1-induced the epithelial mesenchymal transition of alveolar epithelial cells and myofibroblasts trans-differentiation. Then, mogrol was given after intratracheal instillation of bleomycin in mice. Results showed that mogrol treatments (10 mg/kg/d) improved characteristic changes in histopathology, inflammation infiltration and collagen deposition in lung tissues, and that mogrol significantly inhibited TGF-β1-Smad2/3 pathway, restored NOX4 abnormal expression but promoted AMPK phosphorylation. Further research identified that co-treatment with AMPK inhibitor, significantly blocked the anti-fibrotic properties of mogrol, suggesting that the protective effect of mogrol may be attributed to activated AMPK with consequent reduction in inflammatory, fibrosis and oxidative stress. Overall, Siratia grosvenorii effectively protects against lung fibrosis via AMPK activation and amelioration of TGF-β1 signalling pathway.