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

Abstract

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.

Mingjing granule inhibits the subretinal fibrovascular membrane of two-stage laser-induced neovascular age-related macular degeneration in rats

“… Yang et al (2019) reported that wedelolactone reversed the increase of bleomycin-induced fibrosis markers collagen-1 and α-SMA, and the decrease of anti-fibrosis markers E-cadherin, and it significantly prevented the phosphorylation of TGF-β1 and Smad2/3. Karunarathne et al (2023) found that rutin attenuated the gene expression of fibronectin, elastin, collagen-1, and TGF-β, as well as myoblast differentiation from MRC-5 lung fibroblast cells accompanied by the downregulation of α-SMA.…”

Modified Qing-Zao-Jiu-Fei decoction attenuated pulmonary fibrosis induced by bleomycin in rats via modulating Nrf2/NF-κB and MAPKs pathways

“…Sesamin, isolated from Sesami Nigrum Semen , protected against the airway fibrosis induced by ovalbumin via reducing the activation of myofibroblast and the accumulation of collagen via modulating the TGF-β1/Smad3 pathway [ 51 ]. Rutin, another major compound of QZJFD and MQZJFD ameliorated the lung fibrosis induced by BLM in mice through suppressing the TGF-β1/α-SMA/Col I and III pathway [ 52 , 53 ]. Glycyrrhizic acid was also reported to alleviate BLM-induced pulmonary fibrosis in mice and rats [ 54 , 55 ].…”