Amelioration of bleomycin induced pulmonary fibrosis by administration of Salvianolic acid B in mice

Abstract

Pulmonary fibrosis is the end‑stage manifestation of wide range of respiratory diseases and during pulmonary fibrosis, pulmonary inflammation and epithelial‑mesenchymal transition (EMT) play important roles. Salvianolic acid B (SAB) from the herb Salviae miltiorrhiza has been reported to possess an excellent anti‑inflammatory, antifibrotic and antioxidant activity. The present study aimed to investigate the ameliorative effect of SAB on bleomycin induced pulmonary fibrosis in mice. Adult albino mice were divided as SHAM/control group (saline alone), BLM group (bleomycin @ 1mg/kg intratracheally once) and SAB groups (BLM challenged once and SAB administration in three dosages @ 5, 10 and 15 mg/kg intraperitoneally daily for 30 days). Lungs wet/dry ratio and protein concentration in bronchoalveolar lavage fluid, MPO activity, oxidative stress markers, hydroxyproline assay, levels of inflammatory cytokines (TNF‑α, IL‑6 and TGF‑β1), NF‑κB activity, histopathology, immunostaining (E‑cadherin, vimentin and alpha ‑smooth muscle actin) and ultrastructural changes were studied. SAB showed anti‑inflammatory and anti‑fibrotic effects through inhibition of inflammatory cell infiltration, alveolar structure disruption, and collagen deposition and the expression of several fibrogenic cytokines. SAB also up‑regulate E‑cadherin and down‑regulated vimentin and alpha‑smooth muscle actin expression. In conclusion, Salvianolic acid B is effective in alleviating the BLM induced lung fibrosis through suppression of oxidative stress, inflammation, histological, ultrastructural changes and EMT.

Keywords

• Bleomycin
• Epithelial‑mesenchymal transition
• Mice model
• Pulmonary fibrosis
• Salvianolic acid B.