Neohesperidin inhibits TGF-β1/Smad3 signaling and alleviates bleomycin-induced pulmonary fibrosis in mice.

Idiopathic pulmonary fibrosis (IPF) is a fatal growing problem, with limited therapeutic options. Transforming growth factor beta 1 (TGF-β1) plays a critical role in many pathological processes that characterize pulmonary fibrosis. Effective and well-tolerated antifibrotic agents that interfere with TGF-β1 signaling would be an ideal treatment but no such treatments are available. In this study, we identified that the natural compound, neohesperidin, antagonizes TGF-β1/Smad3 signaling. We found that neohesperidin not only inhibited the TGF-β1-induced injury to alveolar epithelial cells but also decreased the TGF-β1-induced myofibroblast differentiation, extracellular matrix production, and fibroblast migration. Furthermore, we obtained in vivo evidence that neohesperidin treatment inhibited bleomycin-induced lung injuries and even attenuated established pulmonary fibrosis in mice. Our data suggest that neohesperidin can target the critical signaling pathway and profibrogenic responses in progressive pulmonary fibrosis and may have a potential use in treatment.