Comparison of the anti-inflammatory and antilipidemic activity of diosmin and saroglitazar in a model of nonalcoholic fatty liver induced by a high-fat diet in Wistar rats.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is the most common liver-related metabolic disorder in the world, with a global prevalence of 25%. Compounds with anti-inflammatory, lipid-lowering, and insulin-sensitizing properties can be used for the prevention or treatment of NAFLD. Therefore, this study was conducted to investigate the effect of saroglitazar (a dual PPARα/γ agonist) and diosmin (a flavonoid) on non-alcoholic fatty liver induced by a high-fat diet (HFD) in Wistar rats.

MATERIALS AND METHODS: Forty male Wistar rats (6-8 weeks old) were fed an HFD to induce NAFLD. After 7 weeks, rats were divided into four groups: group1 was fed HFD, and the other groups received HFD+saroglitazar, HFD+diosmin, and HFD+ saroglitazar+diosmin. We examined body and liver weight, histopathology, serum levels of liver enzymes (ALT and AST), and lipid profiles (LDL-C and HDL-C) using the standard protocols. qRT-PCR was also used to examine the expression of PPARα, PPARγ, SREBP1c, FAS, ACC, CPT1α, and pro-inflammatory genes (IL6, TNFα, and TGFβ).

RESULTS: Rats fed the HFD showed characteristics of NAFLD (pathologically and biochemically). Administration of saroglitazar and diosmin alone caused a significant decrease in the levels of PPARγ, SREBP1c, FAS, ACC, ALT, AST, LDL-C, and pro-inflammatory genes and a significant increase in PPARα, CPT1a, and HDL-C in comparison with the HF group (P<0.05). Their combined effect was more evident.

CONCLUSION: Our results showed that diosmin, like saroglitazar, significantly ameliorated inflammatory and lipid profiles in HFD-induced NAFLD, suggesting that diosmin, as a natural compound, could be a suitable alternative to saroglitazar.