Aims: To identify the therapeutic effects and mechanism of CycloZ on idiopathic pulmonary fibrosis using bleomycin (BLM)-induced pulmonary fibrosis in mice.

Methods: Two different methods were used. First, ICR mice were injected intravenously with BLM (75 mg/kg) and then orally administered CycloZ (15 mg/kg/day) or pirfenidone (300 mg/kg/day) for 28 days. Second, C57BL6/J mice were intratracheally injected with BLM (0.03 IU/head) and were then orally administered CycloZ (15 mg/kg/day) or nintedanib (60 mg/kg/day) for 14 days, starting 7 days after the intratracheal instillation of BLM. Lung functions and micro-CT imaging analyses were performed before sacrifice, and molecular features of pulmonary fibrosis in the lung tissues were analyzed.

Results: In both experimental schemes, CycloZ improved lung compliance, elastance, and increased the aeration area of the lung. It also reduced molecular fibrotic features such as excessive inflammatory cytokines, extracellular matrix, and mesenchymal markers. These beneficial effects of CycloZ were also observed in aged mice, and were comparable to the effects of currently used drugs pirfenidone and nintedanib.

Conclusions: Our data supports the beneficial effects of CycloZ in reversing the expression of multiple genes affected by the fibrotic agent BLM, indicating its potential as a new drug for the treatment of IPF.