Hirsutella sinensis mycelium polysaccharides attenuate the TGF-β1-induced epithelial-mesenchymal transition in human intrahepatic bile duct epithelial cells

Abstract

Hirsutella sinensis is the anamorph of Ophiocordyceps sinensis, and its mycelia has been used to effectively treat a variety of hepatobiliary diseases in clinical practice. In the present study, we performed a systematic study on the composition and structure of its polysaccharides, and then employed a TGF-β1-induced human intrahepatic bile duct epithelial cell-epithelial-mesenchymal transition (HIBEC-EMT) model to investigate their effects on treating primary biliary cholangitis (PBC) based on hepatic bile duct fibrosis. Four polysaccharide fractions were obtained from H. sinensis mycelia by hot-water extraction, DEAE-cellulose column and gradient ethanol precipitation separation. HSWP-1a was an α-(1,4)-D-glucan; HSWP-1b and HSWP-1d mainly consisted of mannoglucans with a backbone composed of 1,4-linked α-D-Glcp and 1,4,6-linked α-D-Manp residues branched at O-6 of the 1,4-linked α-D-Glcp with a 1-linked α-D-Glcp as a side chain; and HSWP-1c mainly contained galactomannoglucans. These polysaccharide fractions protected HIBECs from a TGF-β1-induced EMT, according to HIBEC morphological changes, cell viability, decreased E-cadherin and ZO-1 expression, and increased vimentin and collagen I expression. Furthermore, the effects of the polysaccharides might be mediated by inhibiting the activation of the TGF-β/Smad signaling pathway, which attenuated hepatic bile duct fibrosis and potential PBC effects.