Alpinetin ameliorates bleomycin-induced pulmonary fibrosis by repressing fibroblast differentiation and proliferation

作者：Huilong Chen, Changyu Liu, Yuan Zhan, Yi Wang, Qiongjie Hu, Zhilin Zeng · 发表于：Biomedicine & Pharmacotherapy · 年份：2024 · DOI：10.1016/j.biopha.2023.116101 · 被引用次数：12 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Lung Cancer Treatments and Mutations、Cystic Fibrosis Research Advances

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible interstitial lung disease with a poor prognosis. Alpinetin (ALP), derived from Alpinia katsumadai Hayata, has shown potential as a therapeutic measure of various diseases. However, the utilization of ALP in managing pulmonary fibrosis and its underlying mechanisms are still not fully understood. METHODS: A well-established mouse model of pulmonary fibrosis induced by bleomycin (BLM) was used in this study. The antifibrotic effects of ALP on histopathologic manifestations and expression levels of fibrotic markers were examined. Subsequently, the impact of ALP on fibroblast differentiation, proliferation, apoptosis, and associated signaling pathways was investigated to elucidate the underlying mechanisms. RESULTS: In the present study, we observed that ALP effectively mitigated BLM-induced pulmonary fibrosis in mice, as evidenced by histopathological manifestations and the expression levels of fibrotic markers. Furthermore, the in vitro experiments demonstrated that ALP treatment attenuated the ability of fibroblasts to differentiate into myofibroblasts. Mechanically, our findings provided evidence that ALP suppressed fibroblast-to-myofibroblast differentiation by repressing TGF-β/ALK5/Smad signaling pathway. ALP was found to possess the capability of inhibiting fibroblast proliferation and promoting apoptosis of fibroblasts induced by TGF-β. CONCLUSION: In general, ALP may exert therapeutic effect...