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.

特发性肺纤维化（IPF）是一种致命的进行性肺疾病，治疗方法有限，而转化生长因子-β1（TGF-β1）在IPF的发病机理中起着核心作用。在这里，我们旨在研究旋覆花（Inula japonica Thunb）的化学成分和生物学活性。通过TGF-β1/ Smad3信号通路确定抗肺纤维化药物的主要化合物。旋覆花提取物图恩 用硅胶柱色谱，ODS中压液相色谱和HPLC分离。通过NMR，MS和圆二色性确定纯度和结构。这些提取物对成纤维细胞的细胞毒性和增殖抑制作用通过MTT法测定。用TGF-β1/ Smad3-荧光素酶报告基因稳定转化的肺成纤维细胞用于筛选对TGF-β1/ Smad3信号通路具有抑制作用的活性成分。实时PCR测定法用于检测所选化合物是否可以干扰成纤维细胞的活化。在从Inula japonica Thunb。提取的19种化合物中，15和17已经显示出TGF-β1/ Smad3途径在成纤维细胞中具有显着的抑制活性。另外，TGF-β1刺激后，成纤维细胞中α-SMA和胶原1的mRNA水平被抑制15和17。总之，Inula japonica Thunb提取物的化学成分。可能是治疗IPF的潜在药物。