The Effect Of Hesperidin On Liver Lipid Metabolism And Inflammatory Reaction Of Rats With Non-alcoholic Fatty Liver And Its Partly Mechanisms Of Action

Non-alcoholic fatter liver disease(NAFLD) is a clinical syndrome with lesion of steatosis and fat storage in hepatic lobules but without alcohol abuse. The pathological features are fatty degeneration of hepatocytes, injury and inflammatory cells infiltration. The disease spectrum is mixed with 4 pathological progresses, including simple fatty liver, non-alcoholic steatohepatitis, fatty liver fibrosis and fatty cirrhosis. Epidemiological survey shows that the prevalence of NAFLD has exceeded those of virus hepatitis and alcoholic liver disease(ALD), becoming a medical and social problem with common concern. In the last twenty years, the sickness rate in China and Asia Pacific region has raised about 9 to 40﹪. Howerver, for a long time, studies have failed to clearly define the molecular theory and the optimal treatment has not been established domestic. Thus, it is very important to study on the pathogenesis and efficiency medicine of NAFLD.Hesperidin is a flavonone derivant, by the formative glycoside of Hesperetin and rhamnosidoglucose. Hesperidin is widely present in legumes,white birch,Labiatae, Papilionaceae, Rutaceae, Citrus Plants. And it is a important element of citrus pulp and peel. Domestic and international previous study found that the main pharmacological effects of Hesperidin are antioxidant property, clean oxyradical, hypolipidemic activity, anti-inflammatory and the protection of liver. The aim of the present study is to explore the therapeutical effects of HDN on NAFLD and to analyze the possible mechanisma of HDN effects in rats fed with high fat diet and sucrose. The main contents are divided into some sections as follows:1. Protective Effect of HDN on non-alcoholic fatty liverThe rats of the model group were fed with high fat diet and sucrose. The rats of HDN group(80,160,320mg/kg) and tiopronin group (60mg/kg) were administrated with related dose of medidine by the end of the 3th week and for six weeks. All rats were sacrificed by the end of the 9th week. HDN effectively reduced the serum ALT, AST. The histopathological analysis showed that HDN can significantly alleviate the symptoms in the hepatopathy rats including hepatic steatosis, lobular inflammatory cells infiltration and necrosis. These results suggested that HDN has positively protective effects on high fat emulsion induced rat fatty liver.2. The effects of HDN on lipid metabolism of non-alcoholic fatty liverHDN effectively reduced the serum TC, TG, LDL-C and FFA levels, and increased serum HDL-C level. Electronic microscope examination showed that the lipid droplets in liver cells become smaller, less, and some cells without lipid droplets in the rats treated with HDN. These results suggested the effects of HDN on non-alcoholic fatty liver might be associated with regulating lipid metabolism and reducing fat deposition.3. The effects of HDN on oxidization of non-alcoholic fatty liverCompared with the model group, the hepatic MDA and serum NO were decreased significantly in administration of HDN, meanwhile the activity of SOD was enhanced, the expression of CYP2E1 in liver tissue was lower by immunohistological staining. Electronic microscope examination suggested mitochondria in the model group showed degenerative changes,while the ultrastructural mitochondrial lesions were effectively lightened in the rats treated with HDN. These results showed the effects of HDN might be associated with its antioxidant proerty, suppress the elevated expression of CYP2E1 as well as protect ultrastructural mitochonalrial lesions.4. The effects of HDN on inflammatory reation of non-alcoholic fatty liverThe levels of TNF-α, IL-6 in serum was remarkably reduced,and the reduction of IL-10 level in serum was elevated. Meanwhile, HDN(320mg/kg) effectively depressed abnormally high expression of MCP-1 mRNA and NF-κB in hepatic tissue. These analyses suggested HDN could downregulate the cytokine and relieve inflammatory reaction to prevent the liver.5. The effects of HDN on expression of PPAR-αand CPT-1 of non-alcoholic fatty liverCompared with the normal group, the mRNA expression of PPAR-αand CPT-1 were obviously decreased in model group. RT-PCR analysis showed HDN(320mg/kg) significantly increase the mRNA expression of PPAR-αand CPT-1. These results suggested the effects of HDN on non-alcoholic fatty liver might be associated with upregulating the mRNA expression of PPAR-αand CPT-1.To sum up, HDN has positively therapeutical effects on experimental non-alcoholic fatty liver model. The results suggested that its mechanism of action might be associated with the ability to regulate lipid metabolism, decreasing lipid peroxidation, downregulating CYP2E1 expression, ameliorating inflammation in hepatocytes.