Protective effects of heterophyllin B against bleomycin-induced pulmonary fibrosis in mice via AMPK activation

Wen Shi, Jiatong Hao, Yanliang Wu, Chang Liu, Kuniyoshi Shimizu, Renshi Li, Chaofeng Zhang

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14 Citations (Scopus)

Abstract

Pulmonary fibrosis (PF) is a chronic interstitial lung disease with unknown etiology. In the present study, we evaluated the anti-fibrotic effects of heterophyllin B, a natural product from Radix Pseudostellariae having anti-inflammatory and tyrosinase inhibitory activities. In bleomycin (BLM)-induced PF mouse model, heterophyllin B treatments (5 or 20 mg/kg/d) significantly attenuated BLM-induced alveolar cavity collapse, inflammatory cell infiltration, alveolar wall thickening and collagen deposition. When compared to model group, heterophyllin B treatments also increased adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation levels by 359% (P < 0.001) and reduced the expression of stimulator of interferon genes (STING) by 73% (P < 0.001). Furthermore, co-administration of heterophyllin B with AMPK inhibitor dorsomorphin (Compound C) significantly blocked the improvement effects of heterophyllin B on BLM-damaged lung tissue, and also increased the protein expression of STING which was inhibited by heterophyllin B in fibrotic lungs (P < 0.001). It is known that alveolar epithelia and lung fibroblasts exert prominent roles in the fibrosis progression. In the present study we found that, in vitro, heterophyllin B significantly inhibited alveolar epithelial mesenchymal transition (EMT) and lung fibroblast transdifferentiation. We also found that the inhibition of heterophyllin B on lung fibroblast transdifferentiation and STING expression was reversed by Compound C. To summarize, heterophyllin B exhibited protective effects on BLM-induced lung fibrosis potentially by inhibiting TGF-Smad2/3 signalings and AMPK-mediated STING signalings.

Original languageEnglish
Article number174825
JournalEuropean Journal of Pharmacology
Volume921
DOIs
Publication statusPublished - Apr 15 2022

All Science Journal Classification (ASJC) codes

  • Pharmacology

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