Astaxanthin Alleviates Bleomycin‐Induced Pulmonary Fibrosis in Mice by Suppressing the Fibroblast‐to‐Myofibroblast Transition and Collagen Deposition

Idiopathic pulmonary fibrosis (IPF) is a progressive and fibrotic lung disease characterized by epithelial injury, inflammatory cell infiltration, fibroblast activation and extracellular matrix deposition. Currently, the treatments for IPF have significant adverse effects. Astaxanthin (AST) is a natural xanthophyll carotenoid with unique antioxidant and anti-inflammatory properties. This study investigated the therapeutic potential of AST against pulmonary fibrosis using both in vivo (bleomycin-induced mouse model) and in vitro (TGF-β1-induced HFL1 fibroblasts) approaches. Results showed that AST significantly improved lung function and attenuated fibrosis in mice, as evidenced by improved respiratory function, reduced histological damage, and decreased expression of fibrosis markers (Col1, Col3, α-SMA, FN). Consistent with in vivo findings, AST suppressed the TGF-β1-induced differentiation of fibroblasts into myofibroblasts in HFL1 cells as determined by western blot, immunofluorescence, and quantitative RT-PCR. Furthermore, transcriptome analysis revealed multiple key genes (e.g., LUM and INHBB) and potential pathways (including TGF-β signaling pathway, extracellular matrix (ECM) remodeling pathway) involved in the regulatory effects of AST on pulmonary fibrosis. These findings demonstrate that AST alleviates BLM-induced pulmonary fibrosis by inhibiting the fibroblast-to-myofibroblast transition. This study supports the development of AST as a functional food for IPF management, providing a new strategy for alleviating pulmonary fibrosis.