Research Article Details

Article ID: A01095
PMID: 34870551
Source: Pharm Biol
Title: Ellagic acid protects against non-alcoholic fatty liver disease in streptozotocin-diabetic rats by activating AMPK.
Abstract: 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-α (62%), and IL-6 (57.2%) and the nuclear activity of NF-κB 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 PPARα (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.
DOI: 10.1080/13880209.2021.1990969

Strategy ID Therapy Strategy Synonyms Therapy Targets Therapy Drugs
S02 Enhance lipid metabolism triglyceride-lowering; lipid tolerance; lipid metabolism 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; Details
S04 Anti-oxidative stress oxidative stress α-tocopherol: antioxidant Vitamin E Details

Target ID Target Name GENE Action Class UniProtKB ID Entry Name
T08 Tumor necrosis factor TNF inhibitor Cytokine P01375 TNFA_HUMAN Details
T01 5'-AMP-activated protein kinase subunit beta-1 PRKAB1 activator Kinase Q9Y478 AAKB1_HUMAN Details
T18 Acetyl-CoA carboxylase 1 ACACA inhibitor Enzyme Q13085 ACACA_HUMAN Details
T20 Fatty acid synthase FASN inhibitor Enzyme P49327 FAS_HUMAN Details

Diseases ID DO ID Disease Name Definition Class
I05 9352 Type 2 diabetes mellitus A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus Details

Drug ID Drug Name Type DrugBank ID Targets Category Latest Progress
D328 Serine Chemical drug DB00133 SRR Improve insulin resistance Under clinical trials Details
D182 Insulin Biological drug DB00030 INSR agonist; CPE modulator&product of -- Under clinical trials Details
D158 Glutathione Chemical drug DB00143 MGST3; HPGDS; GSTM2; GSTM5; GPX7 cofactor; MGST2; GSS; GSTM1; GSTK1; GSTM3; GSTM4; GPX1 cofactor; GPX2 cofactor; GPX3 cofactor -- Under clinical trials Details