The Protective And Therapeutic Effects Of Total Flavonoids Of Litsea Coreana Level On Alcoholic Fatty Liver And Its Mechanisms

Alcoholic fatty liver,is frequent in alcoholic liver diease,which is caused by alcohol abusing and characterized by hepatocyte steatosis,hepatocyte damage as well as inflammatory cell infiltration.The fatalness of liver steatosis caused by alcohol that occur liver-failure or liver cirrhosis is higher than that of simple bullous liver steatosis. Pure alcoholic fatty liver may be completely recovered if it could be detected in early stage and be treated in time.On the contrary,it could develop into alcoholic hepatitis, alcoholic hepatic fibrosis and even cirrhosis,where it is difficult to recover the pathological changes.Thus,it is important to study on the pathogenesis and efficiency medicine of AFL.Thus far,no therapy for AFL has clearly been proven effective.Baopizhang(also called Laoying tea) is the leaf of Litsea Coreana level which distributes in Sichuan,Guizhou and south of Anhui province in China.Boapizhang had been traditionally used in China as a health protective tea for many years. Previously report demonstrated that Baopizhang had antioxidant properties.Our previous study showed its mainly active composition is total flavonoids and had anti-inflammatory effects.Furthermore,TFLC had preventive effects on nonalcoholic steatohepatitis.The aim of the present study is to produce a practical and repeatable experimental rat model for steatohepatitis and use this model to explore the preventive effects of total flavonoids of Litsea CoreanaLevel(TFLC) on AFL and its mechanisms of action.The main contents are divided into some sections follows:1.The establishment rat model of AFL.In this study,the rat model of AFL can be developed by intragastric alcohol of increasing concentration gradually and fat emulsion twice a day for 6 weeks.The results showed that serum levels of ALT,AST,ALP,γ-GT,TG,TC and hepatic levels of TG,TC of the model groups markedly increased.Morphological evaluation also revealed that inflammation and necrosis were reproduced in this model.In conclusion, a new rat model of alcoholic fatty liver was established by feeding rats with alcohol and fat emulsion via gavage.This model provides new opportunities to study the pathogenesis and treatment of metabolic syndrome associated with steatohepatitis.2.Preventive Effects of TFLC on alcoholic fatty liverThe preventive effects of TFLC were evaluated in AFL model in rats for 6 weeks. TFLC(100,200,400 mg/kg) was administrated via gavage daily at the beginning of the experiment.Serum levels of ALT,AST,ALP,γ-GT decreased significantly in administration of TFLC(200,400mg·kg^-1),both serum and hepatic levels of TG,TC,FFA markedly reduced.The histopathological analysis suggested that TFLC could significantly ameliorate fatty degeneration of hepatocytes.These results suggest that TFLC has positively preventive effects and treatment effects on alcoholic fatty liver.3.The mechanisms of TFLC prevent alcoholic fatty liver in ratsThe elevation of serum NO,iNOS and both of the serum and hepatic TNF-α,IL-1β,MDA were significantly reduced and the reduction of SOD and GSH-PX contents were increased after TFLC treatment.Meanwhile,TFLC can inhibit the hepatocyte cytochrome P450 IIE1 expression.Electronic microscope examination suggested mitochondria in the model rats showed degenerative changes with rarefied matrix and loss of cristae.These changes were prominent in most of the mitochondria in the model rats,while the ultrastructural mitochondrial lesions were significantly lightened in the rats treated with TFLC.These results suggested the preventive effects of TFLC on alcoholic fatty liver might be associated with its antioxidant effects,the ability to reduce NO,iNOS and TNF-αproduction,suppress the elevated expression of CYP2E1 and protect ultrastructural mitochondrial lesions.To sum up,a new rat model of alcoholic fatty liver was established by feeding rats with alcohol and fat emulsion via gavage.This model is more likely to reproduce the key features of AFL in humans.TFLC has the obviously preventive effects on experimental AFL model.The results suggested that its pharmacological mechanism might be related with associated with adapting blood lipid component and its antioxidative activity,ability to regulate liquid metabolism,reduce NO,iNOS and TNF-αproduction,down-regulate CYP2E1 expression and protect ultrastructural mitochondrial lesions.