Capparis spinosa improves non-alcoholic steatohepatitis through down-regulating SREBP-1c and a PPARα-independent pathway in high-fat diet-fed rats

Abstract

Objective: Non-alcoholic steatohepatitis (NASH) has become a global medical problem. Currently, there is no approved pharmacologic treatment for this condition. Previous studies have suggested that in the pathogenesis of this disease, regulatory pathways associated with de novo lipogenesis and β-oxidation pathways genes are misregulated. Capparis spinosa (CS) belongs to the family of Capparidaceae and is a traditional plant used to treat various diseases, particularly dyslipidemia. The compounds and extracts of this plant in In vivo and in vitro studies resulted in a reduction in lipid profiles and glucose. However, the mechanism of these effects remains unknown. This study aimed to evaluate the effects of (CS) fruit extract on NASH compared to fenofibrate and explored the related molecular mechanism.

Results: In the rats (n = 40) model of NASH, biochemical and histopathological examinations 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 sterol regulatory element-binding protein-1c (SREBP-1c) (p < 0.001), acetyl-CoA carboxylase (ACC) (p < 0.001), and up-regulated Carnitine palmitoyltransferase I (CPT1) expression (p < 0.001). In conclusion, CS has favorable therapeutic effects for NASH, which was associated with ameliorating steatosis and fibrosis via regulation of the DNL and β-oxidation pathway genes.

Keywords: ACC; CPT1; Capparis spinosa; Fenofibrate; NASH; PPARα; SREBP-1c.

Fig. 1

Effect of Capparis spinosa fruit extract and fenofibrate on the body weight (a), liver weight (b), liver index (c), liver TG content (d), sterol regulatory element-binding protein 1c (SREBP1c) (e), acetyl-CoA carboxylase (ACC) (f), peroxisome proliferator-activated receptor α (PPARα) (g), carnitine palmitoyltransferase 1 (CPT1) (h) mRNA expression in NASH model rats during 12 weeks of treatment. Bars represent the mean ± SD of the variables in each group (n = 8). NC, normal control; HF, high fat; CS, Capparis spinosa; FENO, fenofibrate. *p < 0.05; **p < 0.01; ***p < 0.001 and ns: nonsignificant. I Significantly different from NC at end of week 6; II Significantly different from NC after 12 weeks and III significantly different between NC, HF + FENO, and HF + CS vs. HF at end of week 12 (p < 0.001)

Fig. 2

Upper panel: Macroscopic observation of the livers of the HF group showed a grossly larger and beige in color compared with the NC group. Lower panel: Representative images of hematoxylin–eosin-stained sections of liver tissue in different groups at the end of treatments with 100X magnification. A: accumulation of RBCs; I: inflammation; S: steatosis. NC normal control, HF high fat, CS Capparis spinose, FENO fenofibrate