Capparis Spinosa Improves Non-Alcoholic Steatohepatitis Through Down-Regulating SREBP-1c and a PPARα-Independent Pathway in High-Fat Diet-Fed Rats
Abstract Background: Non-alcoholic steatohepatitis (NASH) has become a global medical problem. Currently, there is no approved pharmacologic treatment for this condition. This study aimed to evaluate the ameliorative effects of Capparis spinosa (CS) on NASH in comparison to fenofibrate.Methods: An animal model of NASH was developed using a high-fat (HF) emulsion. Fatty liver rats were treated with aqueous extract of CS fruit or fenofibrate in parallel to the HF for six weeks. Animals were examined for weight gain, serum biochemistry, insulin sensitivity, hepatic triglyceride (TG) content, histopathological changes as well as gene expression of sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), peroxisome proliferator-activated receptor α (PPARα) and Carnitine palmitoyltransferase I (CPT1) in liver.Results: Fasting blood sugar, insulin level, body and liver weight, activities of liver enzymes, hepatic triglyceride (TG) content as well as serum lipids were decreased following six weeks CS and fenofibrate treatments compared to the HF administration alone. Histopathological examinations also showed that liver steatosis, inflammation and hepatic fibrosis were markedly attenuated in response to CS and fenofibrate interventions. At the molecular level, CS treatment down-regulated SREBP1c, ACC and up-regulated CPT1 expression, but did not show a significant effect on PPARα. In contrast, fenofibrate treatment induced the expression of all studied genes in fatty liver rats.Conclusions: These findings indicated the favorable therapeutic effects of CS fruit extract on liver damages associated with NASH. The beneficial effects of CS on lipid accumulation and steatosis were comparable to those of fenofibrate.