polysaccharides ameliorated carbon tetrachloride-induced liver fibrosis through modulating inflammation and apoptosis

Liver fibrosis is a serious global public health problem, owing to a lack of effective treatment. Coprinus comatus polysaccharides (CP), isolated from C. comatus , possess multiple biological activities. In our work, water-soluble polysaccharides (CPa) from CP were obtained by column chromatography. We attempted to investigate the anti-liver fibrosis ability of CPa and the underlying mechanisms of its activity against liver fibrosis in vivo and in vitro , as well as its structure. In vivo results showed that CPa reduced the release of inflammatory factors and apoptosis by modulating the TLR4/MyD88/NF-κB, Bcl-2/Bax and caspase family signaling pathways, thereby attenuating serum enzymes, ROS, α-SMA, collagen III, TGFβ1, p-Smad3, and collagen volume fraction, and increasing the defense capacity of the antioxidant defense system in tetrachloride (CCl 4 )-induced liver fibrosis mice. The in vitro result was used to verify that, in vivo , CPa regulated the TLR4/MyD88/NF-κB, Bcl-2/Bax and caspase family signaling pathways to prevent the activation of HSCs and accelerate HSCs apoptosis in activated LX-2 cells. Thus, CPa could attenuate liver fibrosis by mediating inflammation and apoptosis. Meantime, the structural analysis showed that CPa is a polysaccharide with α- and β-configurations including Fuc, Man, Gal and Glc with a M w of 524 kDa. These findings indicate that CPa could be developed into functional foods and drugs against liver fibrosis. Liver fibrosis is a serious global public health problem, owing to a lack of effective treatment.