Oleuropein Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Mice by Targeting TGF-β1 Signaling Pathway

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by the accumulation of fibrotic tissue in the lungs, leading to impaired gas exchange and respiratory failure, with a poor prognosis and limited treatment options. Oleuropein, a compound extracted from olive leaves, demonstrates a range of pharmacological activities, including benefits for non-alcoholic fatty liver disease and cardiac fibrosis. This study investigates the therapeutic potential of oleuropein for IPF and its underlying mechanisms. We first established a bleomycin-induced mouse model of pulmonary fibrosis and evaluated the in vivo efficacy of oleuropein. Our findings demonstrated that oleuropein significantly alleviated lung fibrosis and improved pulmonary function. Through in vitro experiments, we found that oleuropein inhibited TGF-β1-induced fibroblast migration, activation, autophagy, and apoptotic resistance, and mechanistically, oleuropein could regulate the TGF-β1/Smad and TGF-β1/mTOR signaling pathways in fibroblasts. Additionally, molecular docking analysis indicated that FAP-α is a potential target of oleuropein, displaying strong binding affinity. The effects of oleuropein on fibroblasts were markedly disrupted in FAP-α knockout cells. In conclusion, oleuropein exerts its beneficial effects by targeting FAP-α and inhibiting TGF-β1-related signaling pathways, improving the pathological characteristics of pulmonary fibrosis in mouse models, and demonstrating promising application prospects for the treatment of IPF.