Protective Effects Of Polysaccharides From Yu-ping-feng Powder On Liver Fibrosis In Rats And Its Partly Mechanisms Of Action

Hepatic fibrosis, a dynamic process caused by various chronic liver injuries, is predominantly characterized by excessive accumulation of extracellular matrix (ECM) caused by both an increased synthesis and decreased or unbalanced degradation of extracellular matrix.In recent years,with the pathogenesis of hepatic fibrosis have been making condsiderable progress, liver fibrosis is considered reversible. TGF-β1 is multifunctional peptide growth factor with a wide range of potential effects on growth,differentiation,extracellular matrix deposition and immune response.It changes extracellular matrix synthesis of the normal balance between decomposition and synthesis.Increasing the matrix synthesis and corresponding reducing the total proteolytic activity of ECM result in the formation of reticular fibers.Under normal circumstances, TGF-β1 has hardly expressed in liver,which is marked increased in its expression,now TGF-β1 is considered the formation of liver fibrosis are key factors.Recently, Chinese herbal medicine has become of interest in hepatic fibrosis therapy from laboratory discovery to clinical evaluation,it has a broad prospect of development.Yupingfengsan (YPF, Yu-Ping-FengPowder) is an officially approved herb formula in China consisting of root of Astragalus membranaceus, rhizome of Atractylodes macrocephaia and root of Raidix Saposhnikoviae, recorded originally from the book Danxi's Experiential Therapy. YPF is commonly used to treat biomedically defined disorders such as upper respiratory tract infection, bronchial asthma, glomerulonephritis, chronic urticaria and allergic rhinitis, et al. However, to our knowledge, little information is known about effects of its active components on hepatic fibrosis.We have previously separated several polysaccharide fractions from YPF and confirmed YPF-P was the most active fraction with immunomodulating effects in cyclophosphamide-treated mice. Furthermore, YPF-P presented hepato-protective effect on acute liver injury induced by carbon tetrachloride (CCl4), D-galactosamine or Bacillus Calmette Guerin-lipopolysaccharide by inhibition effect of lipid peroxidation, as we reported. In present study, we aimed to investigate the prevention effects of YPF-P on rat liver fibrosis induced by CCl4 as well as its possible mechanisms.The main contents are divided into three sections,as follows:1. Protective Effects of YPF-P on CCl4-induced hepatic fibrosis in rats.The test result had displayed that, Compared with model group, YPF-P treatment significantly reduced the CCl4-induced elevated liver index,serum ALT,AST, liver MDA,Hyp content and increased SOD in liver tissue. The histopathological analysis suggested that YPF-P reduced the degree of liver fibrosis and improved alterations in the liver structurein rats.These results suggest YPF-P had obvious protective effects on CCl4-induced hepatic fibrosis in rats.2. The mechanisms of YPF-P protect CCl4-induced hepatic fibrosis in rats.Compared with model group, YPF-P treatment effectively reduced the protein expression of NF-κB p65 and TGF-β1 as well as TGF-β1 mRNA. The test result had displayed that YPF-P could inhibit expression of TGF-β1 and NF-κB,which was probably one of the anti-hepatic fibrosis mechanisms of YPF-P.3. Effect of YPF-P on HSC-T6 proliferation and apoptosis in vitroUsing MTT method base exogenous TGF-β1-stimulating factor to stimulate HSC-T6 model group.Observing effect of YPF-P on proliferation of HSC-T6 stimulated with TGF-β1. FCM showed the cell apoptisis ratio of YPF-P(10,20,40,80mg·L -1)is significantly higher compared with the control group.These results suggest YPF-P could significantly inhibit the proliferation and induce the apoptosis of HSC-T6.