LAUSR

Abstract Idiopathic pulmonary fibrosis (IPF) is a fatal and progressive lung disease with limited therapies, while transforming growth factor-β1 (TGF-β1) plays a central role in the pathogenesis of IPF. Here, we aim to investigate the chemical constituents and biological activities of Inula japonica Thunb. on the TGF-β1/Smad3 signaling pathway to determine the principal compounds of anti-pulmonary fibrosis drugs. Extracts of Inula japonica Thunb. were separated by silica gel column chromatography, ODS medium pressure liquid chromatography and HPLC. The purities and structures were established by NMR, MS and circular dichroism. These extracts’ cytotoxicity and proliferation inhibition of fibroblasts were determined by MTT assay. The lung fibroblasts stably transformed with TGF-β1/Smad3-luciferase reporter gene were used to screen for active ingredients that exert an inhibitory effect on the TGF-β1/Smad3 signaling pathway. Real-time PCR assays were used to detect whether the selected compounds could interfere with the activation of fibroblasts. Among the nineteen compounds extracted from Inula japonica Thunb., 15 and 17 have shown significant inhibitory activity of the TGF-β1/Smad3 pathway in fibroblasts. Additionally, mRNA levels of α-SMA and collagen 1 in myofibroblasts after TGF-β1 stimulation were suppressed by 15 and 17. In conclusion, chemical components of the extract from Inula japonica Thunb. might be potential agents for the treatment of IPF.