Hesperidin, a novel candidate for the successful treatment of high fat diet plus ethanol-induced fatty liver disease in mice.

Abstract

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.