Ellagic acid protects against non-alcoholic fatty liver disease in streptozotocindiabetic rats by activating AMPK.

Context: Ellagic acid (EA) is used in traditional medicine to treated hyperlipidaemia. Objective: This study examined if AMPK mediates the anti-steatotic effect of ellagic acid (EA) in streptozotocin (STZ)-induced type 1 diabetes mellitus in rats. Materials and methods: Adult male Wistar rats (130 ± 10 g) were divided into 6 groups (n=8 rats/group) as control, controlþEA, controlþEAþCC an AMPK inhibitor), T1DM, T1DMþEA, and T1DMþEAþCC. The treatments with EA (50 mg/kg/orally) and CC (200 ng/rat/i.p.) were given the desired groups for 12 weeks, daily. Results: In T1DM-rats, EA reduced fasting glucose levels (44.8%), increased fasting insulin levels (92.8%), prevented hepatic lipid accumulation, and decreased hepatic and serum levels of total triglycerides (54% & 61%), cholesterol (57% & 48%), and free fatty acids (40% & 37%). It also reduced hepatic levels of ROS (62%), MDA (52%), TNF-a (62%), and IL-6 (57.2%) and the nuclear activity of NF-jB p65 (54%) but increased the nuclear activity of Nrf-2 (4-fold) and levels of GSH (107%) and SOD (87%). Besides, EA reduced downregulated SREBP1 (35%), SREBP2 (34%), ACC-1 (36%), FAS (38%), and HMG-CoAR (49%) but stimulated mRNA levels of PPARa (1.7-fold) and CPT1a (1.8-fold), CPT1b (2.9-fold), and p-AMPK (4-fold). All these events were prevented by the co-administration of CC. Discussion and conclusions: These findings encourage the use of EA to treat hepatic disorders, and non-alcoholic fatty liver disease (NAFLD). Further in vivo and in vitro studies are needed to validate its potential in clinical medicine. [ABSTRACT FROM AUTHOR]