Investigating rutin as a potential transforming growth factor‐β type I receptor antagonist for the inhibition of bleomycin‐induced lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung condition characterized by the abnormal regulation of extracellular matrix (ECM) and epithelial‐mesenchymal transition (EMT). In this study, we investigated the potential of rutin, a natural flavonoid, in attenuating transforming growth factor‐β (TGF‐β)‐induced ECM regulation and EMT through the inhibition of the TGF‐β type I receptor (TβRI)‐mediated suppressor of mothers against decapentaplegic (SMAD) signaling pathway. We found that non‐toxic concentrations of rutin attenuated TGF‐β‐induced ECM‐related genes, including fibronectin, elastin, collagen 1 type 1, and TGF‐β, as well as myoblast differentiation from MRC‐5 lung fibroblast cells accompanied by the downregulation of α‐smooth muscle actin. Rutin also inhibited TGF‐β‐induced EMT processes, such as wound healing, migration, and invasion by regulating EMT‐related gene expression. Additionally, rutin attenuated bleomycin‐induced lung fibrosis in mice, thus providing a potential therapeutic option for IPF. The molecular docking analyses in this study predict that rutin occludes the active site of TβRI and inhibits SMAD‐mediated fibrotic signaling pathways in lung fibrosis. These findings highlight the potential of rutin as a promising anti‐fibrotic prodrug for lung fibrosis and other TGF‐β‐induced fibrotic and cancer‐related diseases; however, further studies are required to validate its safety and effectiveness in other experimental models. [ABSTRACT FROM AUTHOR]