Feng Siwen, Xu Gonghao, Ding Qi, Shi Yuanyuan
Shenzhen Hospital, Beijing University of Chinese Medicine, Shenzhen, 518172, China.
School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, China.
J Ethnopharmacol. 2025 Mar 13;343:119445. doi: 10.1016/j.jep.2025.119445. Epub 2025 Feb 10.
Pulmonary fibrosis is an irreversible lung disease with a high mortality rate. Zhebeimu (ZBM, Fritillaria thunbergii Miq.) is a Chinese medicine commonly used for the treatment of pulmonary fibrosis in China.
In this study, the protective effect and mechanism of ZBM extract in the treatment of pulmonary fibrosis were investigated in vivo and in vitro.
The protective effect of ZBM extract was assessed using an in vivo model of bleomycin (BLM) tracheal drip and transforming growth factor-β(TGF-β1)-induced fibroblasts to simulate pulmonary fibrosis, and lung function, lung histopathological status and hydroxyproline were tested. Relevant pathways were detected using protein blotting, immunofluorescence and immunohistochemistry.
ZBM extract effectively improved lung function, inflammatory changes and fibrotic deposition in the lungs, and reduced the expression of fibroblast markers in mice. In addition, ZBM extract significantly inhibited TGF-β1-induced hyperphosphorylation of FOXO3, and simultaneously improved the low expression level of FOXO3 prototype protein and significantly reduced the phosphorylation level of PI3K-p85 and AKT1, suggesting that ZBM extract improves lung fibrosis by inhibiting the over-activation of PI3K/AKT/FOXO signalling pathway.
The PI3K/AKT/FOXO signalling pathway is critical for ZBM extract to improve pulmonary fibrosis.
肺纤维化是一种不可逆的肺部疾病，死亡率很高。浙贝母是中国常用于治疗肺纤维化的一种中药。
本研究在体内和体外研究了浙贝母提取物治疗肺纤维化的保护作用及机制。
采用博来霉素气管滴注体内模型和转化生长因子-β1（TGF-β1）诱导的成纤维细胞模拟肺纤维化，评估浙贝母提取物的保护作用，并检测肺功能、肺组织病理学状态和羟脯氨酸。使用蛋白质印迹、免疫荧光和免疫组织化学检测相关通路。
浙贝母提取物有效改善了小鼠的肺功能、肺部炎症变化和纤维化沉积，并降低了成纤维细胞标志物的表达。此外，浙贝母提取物显著抑制TGF-β1诱导的FOXO3过度磷酸化，同时改善FOXO3原型蛋白的低表达水平，并显著降低PI3K-p85和AKT1的磷酸化水平，表明浙贝母提取物通过抑制PI3K/AKT/FOXO信号通路的过度激活来改善肺纤维化。
PI3K/AKT/FOXO信号通路对浙贝母提取物改善肺纤维化至关重要。
