Timosaponin BII inhibits TGF‐β mediated epithelial‐mesenchymal transition through Smad‐dependent pathway during pulmonary fibrosis

Abstract

AbstractPulmonary fibrosis (PF) is a progressive and fatal interstitial lung disease with limited therapeutic options at present, and epithelial–mesenchymal transition (EMT) is recognized as a major cause of lung fibrosis. Our previous work has confirmed that total extract of Anemarrhena asphodeloides Bunge [Asparagaceae] exerted the effect of anti‐PF. As a main constituent of Anemarrhena asphodeloides Bunge [Asparagaceae], the effect of timosaponin BII (TS BII) on drug‐induced EMT process in PF animals and alveolar epithelial cells remains unknown. In this study, we evaluated the effect of TS BII on bleomycin (BLM)‐induced PF. The results showed that TS BII could restore the structure of lung architecture and MMP‐9/TIMP‐1 balance in fibrotic rat lung and inhibit collagen deposition. Moreover, we found that TS BII could reverse the abnormal expression of TGF‐β1 and EMT‐related marker proteins including E‐cadherin, vimentin, and α‐SMA. Besides, aberrant TGF‐β1 expression and phosphorylation of Smad2 and Smad3 in BLM‐induced animal model and TGF‐β1‐induced cell model were downregulated by TS BII treatment, indicating that EMT in fibrosis was suppressed by inhibition of TGF‐β/Smad pathway both in vivo and in vitro. In summary, our study suggested that TS BII could be a promising candidate for PF treatment.