Preventive effects of a fractioned polysaccharide from a traditional Chinese herbal medical formula (Yu Ping Feng San) on carbon tetrachloride-induced hepatic fibrosis.

Objectives: The study was to investigate the prevention effects and possible mechanism of Yu Ping Feng San fractioned polysaccharide (YPF-P) on CCl(4)-induced liver fibrosis in rats.

Methods: YPF-P was prepared from root of Astragalus membranaceus, rhizome of Atractylodes macrocephaia and root of Raidix saposhnikoviae, and compared with polysaccharide from root of Astragalus membranaceus (AP). Hepatic fibrosis was induced by subcutaneous injection with carbon tetrachloride twice weekly for 12 weeks in Sprague-Dawley rats. YPF-P, AP and colchicine were administered intragastrically daily to carbon tetrachloride-treated rats. Histopathological changes of the liver and hepatic stellate cells were evaluated by Masson staining and transmission electron microscopy, respectively. Markers of fibrosis were determined by radioimmunoassay, biochemistry assay and ELISA. The mRNA expressions of tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-13 (MMP-13), procollagen I and collagen III were detected by RT-PCR.

Key Findings: YPF-P dose-dependently alleviated the degree of liver fibrosis and inhibited hepatic stellate cell transformation into myofibroblast-like cells, markedly reduced the elevated levels of hyaluronic acid, laminin, type IV collagen, type III procollagen, hydroxyproline and transforming growth factor beta-1, suppressed procollagen I, collagen III and TIMP-1 expression, and improved the TIMP-1/MMP-13 ratio. MMP-13 expression was only promoted moderately by YPF-P. Compared with AP, YPF-P showed more potency on most markers except laminin, type IV collagen and MMP-13 mRNA.

Conclusions: YPF-P prevented the progress of rat liver fibrosis induced by carbon tetrachloride and had a more potent preventative effect. The preventative effect may be associated with the ability of YPF-P to inhibit the synthesis of matrix collagen and balance the TIMP/MMP system.