Effects And Mechanisms Of Acremoniumterricola Milleretal Mycelium On Chemical Liver Injury And Chemical Hepatic Fibrosis Induced By Carbon Tetrachloride In Rats

Liver fibrosis is now recognized as a common type of liver disease with significant morbidity. Liver fibrosis is a middle stage between chronic liver disease and cirrhosis. It can be defined as a wound healing response to a diversity of chronic stimuli, and it is characterized by an excessive deposition of extracellular matrix (ECM) which mainly consists of type I collagen protein. Current research indicates that hepatic fibrosis is a complicated pathological process which involve in various cytokines and multiple cell signaling pathways. Transforming growth factor (TGF)-β1 is well known as the crucial fibrogenic cytokine promoting liver fibrosis and it can activate hepatic stellate cells (HSCs) which is the principal cellular source of the excess ECM during hepatic fibrosis though TGF-β/Smad signaling pathway . It is also certified that fibrosis is dynamic and can be bidirectional. However, no effective therapies or medicine are available yet. So, finding method to prevent and cure liver fibrosis is extremely urgent.Traditional Chinese medicine has excellent effect on chronic disease and some traditional Chinese herbs are proved having effect in preventing fibrogenesis. Acremoniumterricola Milleretal Mycelium (AMM), a traditional Chinese herb, consist of cordyceps polysaccharide, palmitic acid, unsaturated fatty acid and other beneficial elements to the body , has been used to anti-inflammatory, anti-oxidant, regulate immune system and restore body's function. To further investigate the anti-fibrotic activity of AMM, the present study was designed to detect the effects and mechanisms of AMM on acute liver injury and chemical hepatic fibrosis by carbon tetrachloride in rats.1. Effects of AMM on acute liver injury induced by carbon tetrachloride in mice AMM (500,1000mg/kg) markedly decreased the activities of ALT and AST; The same dose of AMM also significantly reduced the expression of MDA and liver index but enhanced the levels of SOD and GSH-PX in liver homogenates but make no difference to spleen index and thymus index. The results of HE staining showed that AMM could markedly reduce the damage of liver pathology. The results suggest that AMM might exert anti-acute hepatic injury induced by CCl4 in mice and its mechanisms might be associated with its ability to scavenge free radicals.2. Effects of AMM on liver fibrosis induced by carbon tetrachloride in rats According to the examination, treatment with AMM (350 and 700mg/kg) decreased CCl4-induced elevation of serum transaminase activities, hyaluronic acid, laminin and procollagen type III levels, and contents of hydroxyproline in liver tissues. It also restored the decreased SOD and GSH-Px activities and inhibited the formation of lipid peroxidative products during CCl4treatment. Moreover, AMM (350and 700mg/kg) decreased the elevation of TGF-β1 by 19.6% and 34.3%, respectively. In the pathological study, liver injury and the formation of liver fibrosis in rates treated by AMM were improved significantly.3. Effects of AMM on TGF-β/Smad signaling pathway. Immunoblot analysis showed that AMM (350 and 700mg/kg) inhibited Smad 2/3 phosphorylation, and elevated inhibitor Smad7 expression. In conclusion, these results suggested that AMM could protect liver damage and inhibited the progression of hepatic fibrosis induced by CCl4, and its mechanisms might be associated with its ability to scavenge free radicals, decrease the level of TGF-β1 and block TGF-β/Smad signaling pathway.