Reza Afarin - Hyperlipidemia Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Negar Dinarvand - Hyperlipidemia Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Bahar Jaberian Asl - Hyperlipidemia Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Ghazal Orak - Hyperlipidemia Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Elham Shakerian - Hyperlipidemia Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Fatemeh Bineshfar - Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Akram Ahangarpour - Diabetes Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Objective(s): Non-alcoholic fatty liver disease (NAFLD) is the most common liver-related metabolic disorder in the world, with a global prevalence of ۲۵%. 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 (۶–۸ weeks old) were fed an HFD to induce NAFLD. After ۷ weeks, rats were divided into four groups: group۱ 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, SREBP۱c, FAS, ACC, CPT۱α, and pro-inflammatory genes (IL۶, 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, SREBP۱c, FAS, ACC, ALT, AST, LDL-C, and pro-inflammatory genes and a significant increase in PPARα, CPT۱a, and HDL-C in comparison with the HF group (P<۰.۰۵). 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.

Diosmin, Non-alcoholic fatty liver disease, Non-alcoholic steatohepatitis, Saroglitazar, TGFβ