الفهرس 
Aim of the WorkOnly 14 pages are availabe for public view
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Abstract
As the global incidence of obesity has increased, nonalcoholic fatty liver disease (NAFLD) has become a worldwide health concern. NAFLD occurs in children and adults of all ethnicities and includes isolated fatty liver and nonalcoholic steatohepatitis (NASH). Patients with NASH are at risk for developing cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC) and have increased all-cause mortality.
Many pathways have been assumed to be involved in NAFLD progression. Insulin resistance and oxidative stress have been documented as risk factors closely related to the pathogenesis of steatosis and cellular injury. Insulin resistance is reported to be responsible for the accumulation of hepatic fat by increasing lipolysis of peripheral adipose tissue with the resultant increased fat influx into the liver in the form of non-esterified fatty acids (NEFA). Moreover, insulin resistance surprisingly was found to be associated with the enhancement in the rate of de novo triglycerides (TG) synthesis within the liver and inhibition of fatty acid oxidation thereby promoting TG accumulation.
adenosine monophosphate-activated protein kinase (AMPK) (AMPK) plays a key role as a master regulator of cellular energy homeostasis. AMPK is a sensor of low adenosine triphosphate (ATP), activated by adenosine monophosphate (AMP) which makes it more attractive for phosphorylation to the active form. AMPK-P induces the catabolic pathways like lipolysis, mitochondrial biogenesis, glycolysis and fatty acid oxidation. On the other hand, it halts many ATP consuming processes like lipogenesis, gluconeogenesis and protein synthesis. Therefore, AMPK is a target of choice for therapeutic approaches of NAFLD. nicotinamide adenine dinucleotide (NAD+)-dependent type III deacetylase (sirtuin) are a class of proteins that possess either mono-ADP-ribosyltransferase or NAD+-dependent protein deacetylation activity and are implicated in a wide range of cellular processes.
Zingiber officinale rhizomes are reviewed to be one of the widely used traditional therapy medicinal plants. Its rhizomes were studied for its possible activity to treat different diseases like cancer, neurological disorders, inflammation, infection, gastric disorder and DM. Chemical analysis showed that it contains 6-gingerol as a major active compound.
Here, the study investigated the molecular mechanism by which ginger ethanolic extract containing 6-gingerol could beneficially modify the progression of NAFLD compared to pharmaceutical grade Omega-3 fatty acids.
Sixty male rats were divided into six equal groups (N=10) according to the following experimental design:
group 1: Normal control rats (NC)
group 2: Normal rats treated with Omega-3 fatty acids (NO)
group 3: Normal rats treated with the ginger extract (NG)
group 4: NAFLD rats
group 5: NAFLD rats treated with Omega-3 fatty acids (NAFLD-O)
group 6: NAFLD rats treated with the ginger extract (NAFLD-G)
The rats were kept on normal chow or high-fat diet for the whole length of the study (12 weeks). The rats were treated daily by oral gavage through the last 4 weeks of the study (from W8 to W12). The treatment was either with 200 mg ginger extract/kg of rat body weight, with 800 mg omega-3 fatty acids/Kg rat body weight or with a vehicle.
By the end of the experiment, rats were weighed and euthanized. Blood and liver samples were taken for different experiments. Fasting plasma glucose (FPG), plasma total cholesterol (TC), plasma TG, non-esterified fatty acids (NEFA) levels were determined. Plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were assayed. Histological analysis of liver tissues was performed using Sudan 3 or Hematoxylin and Eosin. Hepatic tissue total RNA was extracted and quantitative real-time PCR was performed with Applied Biosystem StepOne PCR for sirtuin 1 (SIRT1), sirtuin 3 (SIRT3) Sirtuin 4 (SIRT4), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), peroxisome proliferator-activated receptor alpha (PPARα), carnitine palmitoyl transferase I (CPT1), sterol regulatory element-binding transcription factor 1 (SREBP-1c), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), tumor necrosis factor alpha (TNF-α), CCAAT/enhancer-binding protein homologous protein (CHOP), inducible nitric oxide synthase (iNOS), transforming growth factor beta 1 (TGFβ1), forkhead box protein O1 (FOXO1), X-box binding protein 1 (XBP-1s), binding immunoglobulin protein (BiP) also known as (GRP78) and carbohydrate-responsive element-binding protein (ChREBP). Western blotting was performed to assay AMPK protein phosphorylation in hepatic tissues.
NAFLD group showed a significant elevation in FPG, TC, TG, NEFA, AST and ALT besides rat body weight gain (BWG) compared to normal healthy rats. The liver histology section showed lipid accumulation in hepatocytes. These pathological changes were significantly corrected by the administration of ginger extract or omega-3 polyunsaturated fatty acid (PUFA). Rats fed with high fat diet (HFD) had significant repression in SIRT1, SIRT-3, SIRT-4, FOXO1, PGC1α, PPARα and CPT1 hepatic genes expressions compared to the normal rats. While it showed significant induction of SREBP-1c, chrEBP, HMGCR, TNF-α, iNOS, CHOP, GRP78, XBP-1 and TGFβ1. Both drugs used in the study caused a significant improvement of the genes’ deregulation to a level comparable to the normal group.