ABSTRACT
OBJECTIVE: To investigate the effect of spearmint oil given at different period of time on pathological changes and the expression of tumor necrosis factor-α(TNF-α), transforming growth factor-β1 (TGF-β1), matrix metalloproteinases-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and α-smooth muscle actin(α-SMA) in mice with bleomycin-induced pulmonary fibrosis. METHODS: Pulmonary fibrosis was induced by intratracheal instillation of bleomycin in ICR mice, then the animals were randomly divided into spearmint oil therapeutic and preventive groups. One day after intratracheal instillation of bleomycin, the mice in preventive group were treated with spearmint oil for 4 weeks; while those in therapeutic groups were given spearmint oil 8 days after administering of bleomycin for 3 weeks. The body weight and mortality were recorded every week; the pathologic changes of lung tissue were observed by HE and Masson staining; the hydroxyproline content was determined; the levels of TNF-α, TGF-β1, MMP-9 and TIMP-1 were measured by ELISA; the expression of α-SMA was observed by immunochemistry. RESULTS: In the preventive groups, spearmint oil of 14, 42 and 140 mg · kg-1 significantly decreased the fibrosis area and reduced collagen deposition while preserving some alveolar structure; spearmint oil of 14 and 140 mg · kg-1 significantly decreased hydroxyproline, TGF-β1 and MMP-9 content; spearmint oil of 14, 42, 140 mg · kg -1 significantly attenuated the expression of α-SMA. In the therapeutic groups, spearmint oil had no significant effect except that the 14 mg · kg-1 group obviously attenuated the expression of α-SMA. CONCLUSION: Spearmint oil given at early period attenuates bleomycin-induced pulmonary fibrosis in mice, the mechanism may include decreasing basemembrane disruption, inhibiting fibroblast, proliferation and transformation, reducing the expression of α-SMA as well as the formation and accumulation of ECM through decreasing the contents of MMP-9 and TGF-β1 in lung tissue. Copyright 2012 by the Chinese Pharmaceutical Association.