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  • Title: Timosaponin BII inhibits TGF-β mediated epithelial-mesenchymal transition through Smad-dependent pathway during pulmonary fibrosis.
    Author: Ding D, Shen X, Yu L, Zheng Y, Liu Y, Wang W, Liu L, Zhao Z, Nian S, Liu L.
    Journal: Phytother Res; 2023 Jul; 37(7):2787-2799. PubMed ID: 36807664.
    Abstract:
    Pulmonary 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.
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