This study aimed to explore the protective effects of
madecassoside (Mad), a
triterpenoid saponin isolated from Centella asiatica herbs, on experimental
pulmonary fibrosis (PF) and underlying mechanisms. PF model was established in mice by endotracheal instillation with
bleomycin (5 mg/kg). Mice were orally administered with Mad (10, 20, 40 mg/kg) and
prednisone (5 mg/kg) for 7 or 21 days. Mad (20, 40 mg/kg) significantly improved lung pathological changes and reduced
collagen deposition. In the aspect of
collagen synthesis, Mad (20, 40 mg/kg) reduced the expressions of α-smooth muscle actin and transforming growth factor-β1 (TGF-β1), and inhibited the phosphorylations of Smad2 and Smad3 in the lung tissues. However, in vitro, Mad showed little effect on TGF-β1-induced phosphorylation of either Smad2 or Smad3 in primary mouse lung fibroblasts. Moreover, Mad (20, 40 mg/kg) attenuated oxidative damage and
inflammation presented at the early stage of PF, evidenced by reduced total leukocytes in the bronchoalveolar lavage fluid, decreased
myeloperoxidase activity and
malondialdehyde level, and increased super-
oxide dismutase activity and
glutathione level in lung tissues. On the other hand, Mad (40 mg/kg) elevated the
matrix metalloproteinase 1/
tissue inhibitor of metalloproteinase 1 ratio in lung tissues of PF mice mainly by downregulating
tissue inhibitor of metalloproteinase 1 expression. The present study demonstrated that Mad can ameliorate PF by preventing the deposition of extracellular matrix, which might be achieved mainly through attenuating
inflammation and oxidative stress and consequent TGF-β1 overexpression.