Oleanolic acid acetate ameliorates bleomycin-induced pulmonary fibrosis through inhibition of epithelial-mesenchymal transition

Abstract

Background: Oleanolic acid acetate (OAA) is a triterpenoid compound derived from Vigna angularis and is known to have various effects such as tumor suppression, kidney protection, and anti-inflammatory effect. However, research on the inhibition mechanisms of OAA in fibrosis is limited. In this study, we investigated the effects of OAA on bleomycin-induced pulmonary fibrosis in mice and its underlying mechanism in vivo and in vitro. Methods: The in vivo effect of OAA was evaluated by measuring histological changes, mRNA, BALF, collagen content and protein expression in bleomycin-indcued pulmonary fibrosis mice. The in vitro effect of OAA was evaluated proliferation, mRNA and protein expression of A549 and NIH3T3 cells were analyzed by CCK-8, real-time PCR and Western blot respectively. Mice were treated with bleomycin and OAA was orally administered for 14 days after bleomycin injection, and A549 and NIH3T3 cells were induced by TGF-b1 for 48 hours. Results: OAA treatment reduced inflammatory cell count, cytokine level and soluble protein accumulation in bronchoalveolar lavage fluid, and ameliorated weight loss and lung weight, lung histopathological abnormality and pulmonary collagen deposition. OAA also inhibited the expression of EMT and fibrotic markers in vivo and in vitro. Moreover, levels of TGF-β1, p-Smad2, and p-Smad3 in vivo and in vitro decreased after OAA treatment. Conclusion: OAA inhibits bleomycin-induced pulmonary fibrosis by inhibiting EMT and may be a novel therapeutic drug for the treatment of idiopathic pulmonary fibrosis.