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Abstract Non alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease which affects 20-30% of population around the world. NAFLD is characterised by the accumulation of fat in the liver more than 5 % by weight. The term NAFLD describes a wide range of liver diseases extending from steatosis (defined by accumulation of fats in hepatocytes) to its more severe form of nonalcoholic steatohepatitis (NASH) and in the end stages to the hepatic cirrhosis and hepatocellular carcinoma. The widely accepted theory is the ―multiple hit theory‖ which explain the pathogenesis of NAFLD. Insulin resistance, obesity, and type 2 diabetes mellitus are linked with NAFLD. The main feautres in the pathogenesis of NAFLD are lipid accumulation, lipotoxicity, and inflammation. Multiple treatments are available for NAFLD. The first step of treatment is usually weight loss through acombination of healthy diet and exercise. Several studies is focusing on several alternative treatments targeting the main pathogenic factors such as insulin-resistance, dyslipidemia and oxidative stress. Several studies highlighted the potential use of microRNAs involved in the NAFLD pathogenesis as therapeutic tools in the management of NAFLD. Natural polyphenols have been found to possess many pharmacological effects on oxidative stress, lipid metabolism, insulin resistance, and inflammation, which are the most important pathological events in the liver diseases. Curcumin, a natural yellow polyphenol compound that is the main active component in turmeric. Curcumin performs many important and therapeutic functions, such as antioxidant, anti-inflammatory, antimicrobial, and anti- cancer. Curcumin play akey role in controlling lipid and glucose metabolism, thus helping to treat many diseases, such as hepatic diseases, diabetes and obesity. The aim of the present work is the study the change in hepatic expression of miRNA- 33a, SREBP-2, Sirt-6 and NF-κB during the treatment of NAFLD in experimental rats by curcumin. The study was conducted on 40 Wistar male rats. Animals will be divided equally into four groups: group І (Control group): will receive standard rat chew diet, group ІI (Fatty liver group): Animals will receive high fat diet (HFD) at the eighth week fatty liver disease will be confirmed by histolopathological examination of the liver through scarification of some rats, group III (DMSO treated group): After NAFLD is established as in group II, rats will be injected intraperitoneally with 1 ml/kg body weight dimethyl sulfoxide (DMSO) day after day for 4 weeks, group ІV (Curcumin treated group): After NAFLD is established as in group II, animals in this group will be injected intraperitoneally day after day for 4 weeks with 100 mg/kg of curcumin dissolved in DMSO. At the end of the experimental period, all the animals will be sacrificed. Blood samples and liver of the rats will be collected for biochemical analysis and hepatic lipid content determination. Liver tissues will be used for determining the gene expression of miRNA-33a, SREBP-2, Sirt- 6 and NF-κB. The present study results showed significant increase in fasting blood glucose, fasting insulin levels, HOMA-IR, cholesterol, triglyceride, LDL cholesterol, ALT, AST activities, hepatic cholesterol and triglyceride content in untreated group compared to control group and this was reversed by curcumin treatment. Also, the results showed upregulation in gene expression of NF-κB, SREBP-2 and miR-33a in untreated group compared to control group. On the other hand, curcumin treatment downregulated the gene expression of NF-κB, SREBP-2 and miR-33a compared to untreated group. The gene expression of Sirt-6 was downregulated in untreated group compared to control group, but using curcumin treatment showed upregulation of gene expression of sirt-6 compared to untreated group. |