Silymarin-loaded chitosan nanoparticles alleviate dyslipidemia, oxidative stress, metabolic disturbance and histopathological injury associated with high fat diet-induced non-alcoholic fatty liver disease in rats

With an increasing incidence of obesity and metabolic syndrome epidemic, nonalcoholic fatty liver disease (NAFLD) continues to be one of the most prevalent liver illnesses worldwide. One of recommended treatment in NAFLD is silymarin. Howerver, the problem is that silymarin has weak water solubility and limited bioavilability. Therefore, prepration of silymarin in nano-formulation would enhance silymarin's therapeutic effects and bioavailability. This study was designed to evaluate the biochemical and molecular effects of silymarin-loaded chitosan nanoparticles (SILCSNPs) in NAFLD treatment in rats. Fifty rats were divided into five groups include: Group 1: Control group, group 2: HFD-induced NAFLD, group 3: HFD-induced NAFLD that orally received nano-chitosan, group 4: HFD-induced NAFLD that orally received nano-silymarin and group 5: HFD-induced NAFLD that orally received silymarin-loaded chitosan nanoparticles (SILCSNPs). The dose of each treatment was 40 mg/kg/day for 60 days. Lipid parameters (triglycerides, total cholesterol), ALT, AST, hepatic (catalase, SOD and MDA) and mRNA expression of lipogenesis-related genes including ACC (acetyl-CoA carboxylase) and FASN (fatty acid synthase) as well as fatty acids catabolism-related genes including CPT-1 (carnitine palmitoyl-transferase I), PPAR-α (peroxisome proliferator-activated receptor alpha) were measured. Histopathological examination of liver was also conducted. A significant elevation in HDL, catalase, SOD, CPT-1, PPAR-α levels as well as substantial reduction in triglycerides, cholesterol, ALT, AST, MDA, ACC and FASN levels were detected in treated groups in compared to the HFD-induced NAFLD group. Histopathological examination of the liver showed histological amelioration in hepatic tissue in treated groups in compared to the HFD-induced NAFLD group. SILCSNPs revealed a significant potential effect against NAFLD metabolic disturbance and considered an advanced trend in NAFLD treatment.