Ellagic acid protects against non-alcoholic fatty liver disease in streptozotocin-diabetic 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, control + EA, control + EA + CC an AMPK inhibitor), T1DM, T1DM + EA, and T1DM + EA + CC. 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-alpha (62%), and IL-6 (57.2%) and the nuclear activity of NF-kappa B 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 PPAR alpha (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.

Automated summary

Ellagic acid (EA) has anti-steatotic effects in streptozotocin-induced type 1 diabetes mellitus in rats, potentially mediated through the AMPK signaling pathway. It reduces blood glucose levels, increases insulin levels, prevents hepatic lipid accumulation, and decreases levels of triglycerides, cholesterol, and free fatty acids. It also reduces oxidative stress and inflammation in the liver.