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-beta (TGF-beta)-induced ECM regulation and EMT through the inhibition of the TGF-beta type I receptor (T beta RI)-mediated suppressor of mothers against decapentaplegic (SMAD) signaling pathway. We found that non-toxic concentrations of rutin attenuated TGF-beta-induced ECM-related genes, including fibronectin, elastin, collagen 1 type 1, and TGF-beta, as well as myoblast differentiation from MRC-5 lung fibroblast cells accompanied by the downregulation of alpha-smooth muscle actin. Rutin also inhibited TGF-beta-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 T beta RI 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-beta-induced fibrotic and cancer-related diseases; however, further studies are required to validate its safety and effectiveness in other experimental models.

Automated summary

In this study, the potential of rutin in attenuating ECM regulation and EMT caused by TGF-beta and its underlying mechanisms were investigated. Rutin was found to inhibit TGF-beta-induced ECM-related genes and EMT processes. Furthermore, rutin attenuated lung fibrosis in a mouse model. Molecular docking analyses suggest that rutin inhibits SMAD-mediated fibrotic signaling pathways. These findings highlight the potential of rutin as a therapeutic option for fibrotic and cancer-related diseases induced by TGF-beta.