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Liver fibrosis is result from the majority of chronic liver,which is characterized by acute liver injury,activating of HSC,increasing and deposition of extracellular matrix in the liver.It is mostly induced by viral hepatitis,alcoholism,iron overload,or drug toxicity. So it is very important clinical significant to control the development and process of liver injury in time.In summary,accumulating evidence suggests that liver fibrosis is reversible and that recovery from cirrhosis may be possible.However,it is still difficult to achieve satisfied therapeutic effect.Bidens bipinnata L.,a species of the genus Bidens（Compositae）,is widely distributed in majority province in China.Bidens bipinnata L.had been traditionally used for many years.It is bitter in taste,neutral in nature and innocuity,and has the effect of heat-clearing, detoxicating and eliminating stasis to subdue swelling.It was largely used to treat hepatitis, inflammation,malaria,hypertension,diabetes,pepticulcer,snake bite,smallpox.Previous report show it has anti-inflammatory,removal of oxygen free radicals and the regulation of the immune.It contains many chemical compositions,such as flavonoid glycoside,saponin,alkaloid, aetherolea.Our previous study show its mainly active composition is total flavones of Bipinnata L （TFB）,which is extracted from the leaves of Bidens pilosa L.TFB has been preliminarily assessed to be of protection against acute liver injury and experimental liver fibrosis by CCl4.To further explore the effect of total flavones of Bidens Bipinnata L（TFB） on immunological liver fibrosis,the immunological model was induced by pig serum in Sprague-Dawley rats.The mechanisms of action of TFB on liver fibrosis by using the methods in vivo and molecular levels were studied.The main contents were divided into some sections as follows:1.Therapeutic effects of TFB on pig serum-induced liver fibrosisThe pig serum was injected into abdominal cavity（0.5 ml,twice a week） for 12 weeks so as to induce hepatic fibrosis,and then the rats were treated with TFB daily for 10 weeks and killed at the 22nd week.Compared with model group,TFB increased weight and inhibited the elevation of index of liver and spleen.Furthermore,TFB treatment significantly reduced ALT,AST,HA,LN,PCⅢ,CⅣcontent in serum and Hyp in liver tissue.Liver histopathological examination showed TFB could also ameliorate fibrogenesis and pseudolobule formation by hematoxylin-eosin（HE） staining and masson staining. These results suggest that TFB has positively preventive effects and treatment effects on immunological liver fibrosis by pig serum.2.The mechanisms of Therapeutic effects of TFB on immunological liver fibrosisFurther study showed that TFB treatment markedly reduced MDA in liver tissue, increased SOD,GSH-Px activity.TFB treatment decreased the expression of protein TGF-β1,α-SMA mRNA in liver by Immunohistochemistry.And then TFB treatment could significantly down-regulated TGF-β1 and Smads2 mRNA expression and up-regulated Smads7 mRNA expression in liver by RT-PCR analysis.In addition TFB treatment decreased the number of activated HSC and increased the quantity of apoptosis HSC by TUNEL andα-SMA staining. Conclusion:TFB significantly had therapeutical effect on immunological liver fibrosis in rats probably by its free-radical scavenging ability,inhibition of HSC TGF-β1/Smads pathway,suppressive effects on HSC proliferation and collagen production,stimulation of activated HSC apoptosis.
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