Luteoloside alleviates bleomycin-induced pulmonary fibrosis in mice via SIRT1-mediated protective effect against alveolar epithelial cell senescence

Abstract The senescence of alveolar epithelial cells plays a central role in the pathogenesis of idiopathic pulmonary fibrosis, a disease currently lacking specific therapeutic approaches. Luteoloside, a flavonoid glycoside compound found in plants such as those from the Asteraceae and Fabaceae families, has various biological activities. This study aimed to explore the anti-senescence and anti-fibrotic effects of luteoloside in experimental pulmonary fibrosis and investigate its underlying molecular mechanisms. Our results indicated that luteoloside attenuated bleomycin-induced pulmonary fibrosis, oxidative stress, and lung senescence in mice. Immunofluorescence analysis revealed that luteoloside reduced AEC senescence, as indicated by decreased P21 expression in SPC⁺ epithelial cells. In vitro, luteoloside removed bleomycin- and oxidative stress-induced AEC senescence and mitochondrial dysfunction. Mechanistically, we proved through the inhibition effect of EX527 that luteoloside’s protective effects were mediated through SIRT1. This study provides new insights into the mechanisms through which luteoloside modulates cellular senescence and pulmonary fibrosis, offering potential pathways for the development of novel therapeutic strategies.