title: Anti-fibrotic effect of Cordyceps sinensis polysaccharide: Inhibiting HSC activation, TGF-β1/Smad signalling, MMPs and TIMPs.
abstract: Cordyceps sinensis has been used to treat liver disease in traditional Chinese medicine for thousands of years. Polysaccharide extracted from cultured Cordyceps sinensis mycelia (CS-PS) is the major active components of cordyceps sinensis with anti-liver injury effects. In the present study, the effects of CS-PS on hepatic stellate cell (HSC) activation, transforming growth factor-β1 (TGF-β1)/Smad pathway, as well as matrix metalloproteinase (MMP) 2, MMP9 and tissue inhibitor of metalloproteinase (TIMP) 1, TIMP2, were investigated in liver fibrosis in rats induced by carbon tetrachloride (CCl4). Colchicine was used as a positive control. The effect of CS-PS inhibition liver injury and fibrosis was confirmed by decreasing serum alanine aminotransferase, aspartate aminotransferase, total bilirubin, hepatic hydroxyproline and increasing serum albumin, as well as alleviation of histological changes, which was comparable to that of colchicine. With CS-PS treatment, hepatic α-smooth muscle actin, TGF-β1, TGF-β1 receptor (TβR)-I, TβR-II, p-Smad2, p-Smad3 and TIMP2 proteins expression were down-regulated comparing to that in CCl4 group. The activities of MMP2 and MMP9 in liver tissue were also inhibited in CS-PS-treated group. It is indicated that the effects of CS-PS anti-liver fibrosis are probably associated with the inhibition on HSC activation, TGF-β1/Smads signalling pathway, as well as MMP2, MMP9 activity and TIMP2 expression.
authors.affiliation: Institute of Liver diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Peng
authors.forename: Xuemei
authors.initials: X
authors.lastname: Li
authors.forename: Qin
authors.initials: Q
authors.lastname: Feng
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.forename: Lili
authors.initials: L
authors.lastname: Xu
authors.forename: Yiyang
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000378:metabolism; D032661:Cordyceps / Q000737:chemistry*; D015536:Down-Regulation / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008516:Medicine, Chinese Traditional; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D011480:Protease Inhibitors; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D019716:Tissue Inhibitor of Metalloproteinase-2; D002251:Carbon Tetrachloride; D020782:Matrix Metalloproteinases
keywords: Cordyceps sinensis polysaccharide; hepatic stellate cell (HSC); liver fibrosis; matrix metalloproteinase (MMP); tissue inhibitor of metalloproteinase (TIMP); transforming growth factor-β1 (TGF-β1)