Inhibition of ginsenoside Re on pulmonary fibrosis induced by bleomycin in mice: Involved in modulating the CX3CL1/CX3CR1 axis

Pulmonary fibrosis (PF) is a common pathological feature of a variety of diffuse, progressive and irreversible pulmonary interstitial diseases, and effective therapeutic agents are currently lacking. Our previous study found that the total ginsenosides can improve pulmonary fibrosis induced by bleomycin in mice. Ginsenosides Re (G-Re) is one of the most abundant active ingredients in total ginsenosides and has a variety of pharmacological activities. This study investigated the inhibitory effect and mechanism of Re on pulmonary fibrosis in mice induced by bleomycin. The effects of G-Re on pulmonary fibrosis were evaluated using lung function measurement, pathological analysis, and detection of deposition of extracellular matrix (ECM). To investigate the mechanisms underlying the anti-pulmonary fibrosis effects of G-Re, chemokine CX3C ligand 1 (CX3CL1) and receptor 1 (CX3CR1), transforming growth factor beta 1 (TGF-β1), mitogen-activated protein kinase 1/2 (MEK1/2), extracellular signal-regulated kinase1/2 (ERK1/2), matrix metalloproteinase 2 (MMP2), and tissue inhibitor of metalloproteinases-1 (TIMP-1) in lung tissues were detected by molecular biology techniques, immunofluorescence and immunohistochemistry. Treatment with G-Re ameliorated pulmonary fibrosis in mice induced by bleomycin. In addition, it downregulated the levels of CX3CL1, CX3CR1, TGF-β1, MEK1/2, and MMP2. It upregulated the level of TIMP-1. These findings indicate that G-Re exerts protective effects against pulmonary fibrosis, likely through suppression of the CX3CL1/CX3CR1 axis and coordinated regulation of the ERK 1/2 signaling pathway and matrix metalloproteinases (MMPs), leading to reduced alveolar basement membrane injury and diminished extracellular matrix (ECM) accumulation in murine lung tissue. • Ginsenoside Re ameliorates the quality of life in mice with pulmonary fibrosis. • Ginsenosides Re can effectively mitigate collagen fiber deposition in the lung tissue of mice with pulmonary fibrosis. • Ginsenoside Re ameliorates pulmonary fibrosis, potentially through the inhibition of the CX3CL1/CX3CR1 axis.