Ganoderic Acid A Inhibits Bleomycin-Induced Lung Fibrosis in Mice.

ABSTRACT

BACKGROUND: To study the protective effects of ganoderic acid A (GAA) on bleomycin (BLM)-induced pulmonary fibrosis. METHODS: ICR mice were intratracheally instilled with BLM to induce pulmonary fibrosis on day 0. Then the mice were orally given GAA (25, 50 mg/kg) or dexamethasone (2 mg/kg). After treatment for 21 days, the mice were sacrificed. Wet dry weight (W/D) ratio of lung was used to detect pulmonary edema. Myeloperoxidase (MPO), interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), and superoxide dismutase (SOD) were detected by enzyme-linked immunosorbent assay. Hematoxylin and eosin staining was used to evaluate the pathological changes. The levels of transforming growth factor ß (TGF-ß), phosphorylated-smad3 (p-smad3), p-IκB, and p-nuclear factor-kappa B (NF-κB) in lung tissue were detected by western blot. RESULTS: GAA treatment significantly improved MPO activity, W/D ratio, and lung histopathology. The protective effect of GAA may be related to downregulation of TNF-α, IL-1ß, IL-6, MDA and upregulation of SOD. In addition, GAA significantly decreased the levels of TGF-ß, p-smad3, p-IκB, and p-NF-κB, compared with those in BLM group. CONCLUSION: GAA has protective effect on BLM-induced lung injury, and TGF-ß/Smad-3/NF-κB signaling pathway may play an important role in the pathogenesis of BLM-induced lung injury.