The effect of Nitrochalcone on biochemical indicators and PPAR-α gene expression in nonalcoholic male NMRI mice steatosis model

Introduction: Non-alcoholic fatty liver disease (NAFLD) is associated with oxidative stress, inflammation, and decrease in peroxisome proliferator-activated receptor alpha (PPAR-α) expression. Nitrochalcone is effective ingredient of chalcones with anti-inflammatory, anti-cancer and anti-hyperglycemic properties. This study examined the effect of intraperitoneal (IP) administration of nitrochalcone in a mouse model with non-alcoholic steatosis. Materials and Methods: In this study, 94 male NMRI mice were assigned to control and experimental groups. The Normal control group (NC) was given normal rodent diet The experimental group was subjected to high fat diet for 4 weeks, which induced NAFLD, then the experimental group was divided in to 5 in vivo subgroups (n=12 in each), High fat (HF) Sham (receiving grapes seed oil), Positive control groups (C+: receiving silymarin (80mg/kg) by intra peritoneal injection (IP)) and Experimental Nitrochalcone groups (EN1, EN2, EN3) receiving nitro chalcone (5, 10 and 20 mg/kg) by IP during 4 weeks. Protective groups received high-fat diet and Nitrochalcone 20 mg/kg simultaneously for 4 weeks. At the end of the treatments, biochemical parameters, liver enzymes, antioxidant enzymes and expression of PPAR-α were determined. Results: The serum levels of some biochemical parameters such as cholesterol glucose, liver enzymes, and insulin significantly increased in the HF group in comparison with the control group (P < 0.001). Nitrochalcone (20 mg/ kg) decreased liver enzymes levels as compared with the HF and Sham group (P < 0.001). The highest percentage of increase in PPARα gene expression was observed in EN3 group, as compared with the controls. Conclusion: HF diet caused steatohepatitis through insulin resistance, impaired lipid profile, increased glucose and liver enzyme levels. Furthermore, the diet decreased antioxidants, adiponectin, leptin and PPARα levels, and made fibrosis in the liver. Nitrochalcone improved this condition in a dose-dependent manner, and resulted in elevated PPARα expression.