HESPERIDIN, A NOVEL CANDIDATE FOR THE SUCCESSFUL TREATMENT OF HIGH FAT DIET PLUS ETHANOL-INDUCED FATTY LIVER DISEASE IN MICE.

Flavonoids have demonstrated beneficial effects in fatty liver disease (FLD). Consumption of flavonoids is associated with several health benefits via their antioxidant and anti-inflammatory activities. The current study aimed to investigate hesperidin and myricetin as new candidates for FLD therapy. Five-week-old female ICR mice were provided a high fat diet (HFD) 60 kcal % fat of total food and daily intragastrically administered ethanol (0.5 g/kg/day) in combination with fenofibrate (40 mg/kg/day) or flavonoids, hesperidin or myricetin (50 and 200 mg/kg/day), for 60 consecutive days. Hepatic histomorphology was observed with oil red O (ORO) staining along with hepatic triglyceride (TG) level, activity of antioxidative enzymes, and mRNA expression of metabolic, antioxidative, and inflammatory genes, including peroxisome proliferator activated receptor-alpha and -gamma 2 (Ppara and Pparg2), sterol regulatory element binding protein-1c (Srebp-1c), acetyl-CoA carboxylase (Acaca), fatty acid synthase (Fasn), CD36 molecules (Cd36), catalase (Cat), superoxide dismutase 1 and 2 (Sod1 and Sod2), glutathione peroxidase 1 (Gpx1), nuclear factor of kappa light polypeptide gene enhancer in B cells 1 (Nfkb1), tumor necrosis factor-alpha (Tnf-α), chemokine (C-C motif) ligand 2 (Ccl2). Fenofibrate, hesperidin, and myricetin improved hepatic histomorphology, restored expression of metabolic genes, improved antioxidative system, and suppressed inflammatory pathways. Interestingly, hesperidin attenuated TG level and down-regulated Ccl2 expression at low dose and reinstated Cat expression better than myricetin. These findings confirm that hesperidin is a promising candidate for FLD therapy. [ABSTRACT FROM AUTHOR]