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Kurarinone Attenuates BLM-Induced Pulmonary Fibrosis via Inhibiting TGF-β Signaling Pathways.

Abstract
Idiopathic pulmonary fibrosis (IPF) is a refractory interstitial lung disease for which there is no effective treatment. Although the pathogenesis of IPF is not fully understood, TGF-β and epithelial-mesenchymal transition (EMT) have been shown to be involved in the fibrotic changes of lung tissues. Kurarinone is a prenylated flavonoid isolated from Sophora Flavescens with antioxidant and anti-inflammatory properties. In this study, we investigated the effect of kurarinone on pulmonary fibrosis. Kurarinone suppressed the TGF-β-induced EMT of lung epithelial cells. To assess the therapeutic effects of kurarinone in bleomycin (BLM)-induced pulmonary fibrosis, mice were treated with kurarinone daily for 2 weeks starting 7 days after BLM instillation. Oral administration of kurarinone attenuated the fibrotic changes of lung tissues, including accumulation of collagen and improved mechanical pulmonary functions. Mechanistically, kurarinone suppressed phosphorylation of Smad2/3 and AKT induced by TGF-β1 in lung epithelial cells, as well as in lung tissues treated with BLM. Taken together, these results suggest that kurarinone has a therapeutic effect on pulmonary fibrosis via suppressing TGF-β signaling pathways and may be a novel drug candidate for pulmonary fibrosis.
AuthorsSoo-Jin Park, Tae-Hyoun Kim, Kiram Lee, Min-Ah Kang, Hyun-Jae Jang, Hyung-Won Ryu, Sei-Ryang Oh, Hyun-Jun Lee
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 16 (Aug 04 2021) ISSN: 1422-0067 [Electronic] Switzerland
PMID34445094 (Publication Type: Journal Article)
Chemical References
  • Flavonoids
  • Transforming Growth Factor beta
  • kurarinone
  • Bleomycin
Topics
  • Animals
  • Bleomycin
  • Cell Line
  • Epithelial-Mesenchymal Transition
  • Flavonoids (pharmacology, therapeutic use)
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Pulmonary Fibrosis (chemically induced, drug therapy, metabolism, pathology)
  • Signal Transduction (drug effects)
  • Transforming Growth Factor beta (metabolism)
  • Mice

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