Barbaloin attenuates pulmonary fibrosis through TGF-β1/Smads/p38 pathway.

Abstract

Barbaloin is one of the main bioactive ingredients extracted from Aloe vera, which has the property of protecting the lung from LPS-induced acute injury; however, the anti-pulmonary fibrosis effect of barbaloin is still unknown. Herein, we present novel data showing the anti-pulmonary fibrosis effect of barbaloin and revealing the possible molecular mechanism. In vivo experiment, oral administration of barbaloin was investigated through paraquat-induced pulmonary fibrosis in mice. In vitro experiment, epithelial-mesenchymal transition (EMT) process and TGF-β1 pathway were investigated in A549 cells for exploring the anti-fibrosis molecular mechanism of barbaloin. Results showed that barbaloin could improve pulmonary fibrosis through improving physiological routine indexes and histopathological lesions of mice in a dose-dependent manner. Hydroxyproline, collagen I, N-cadherin and α-SMA levels were significantly suppressed. Besides, pro-inflammatory cytokines were also improved. In vitro experiment, barbaloin could inhibit the process of EMT through repressing α-SMA, collagen I and N-cadherin and increasing E-cadherin. In addition, barbaloin could repress the expression of p-Smad2/3 and then suppress the process of EMT through intervening TGF-β1-induced canonical pathway. Moreover, MMP-2 and MMP-9 were also inhibited by barbaloin via repressing phosphorylation of p38 through TGF-β1-induced non-canonical axis. Our findings reveal the anti-pulmonary fibrosis effect of barbaloin in vivo and in vitro for the first time. These results indicate that barbaloin may be a promising clinical candidate drug against pulmonary fibrosis.