crocin and Non-alcoholic-Fatty-Liver-Disease

The role of hepatocyte apoptosis and inflammation has been implicated in the progression of nonalcoholic steatohepatitis (NASH). Overproduction of reactive oxygen species (ROS) appears to accelerate these pathways through the activation of Fas receptor signaling. Therefore, we explored the hepatoprotective effects of crocin as a strong free radical scavenger against oxidative damages leading to NASH development.. Thirty-two male mice were randomly divided into control, NASH, NASH + crocin, and crocin groups. They received an intraperi- toneal injection of crocin twice a week, for 3 weeks. For NASH model induction, the animals were fed with a Western diet and exposed to cigarette smoke for 8 weeks. At the end of the experiment, liver histology, biochemical, and biomolecular analyses were done to evaluate the antioxidant, anti-inflammatory, and anti-apoptotic activities of crocin in the NASH model.. Evaluation of the features of the NASH model revealed steatosis, inflammatory infiltrate, and ballooning degeneration. Metabolic dysfunction was associated with elevated serum levels of the lipid profile and decreased hepatic liver enzymes. The increased content of malondialdehyde (MDA) and reduced antioxidant activities confirmed hepatotoxicity induction. There was a significant increase in expression level of Fas, caspase 3, and NF-κB genes that was also associated with elevation in hepatic TNF-α content. Moreover, expression the of Fas receptor protein was significantly detected on the hepatocyte membrane. Treatment with crocin effectively improved NASH-related parameters, and the histopathological findings were also parallel with the resulting changes.. Crocin can be introduced as a candidate hepatoprotective agent against NASH by virtue of its anti-inflammatory, antioxi- dant, and anti-apoptotic properties, possibly through regulation of the Fas death receptor pathway.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Carotenoids; fas Receptor; Male; Mice; Non-alcoholic Fatty Liver Disease; Signal Transduction

Non-alcoholic fatty liver disease (NAFLD) is closely linked to obesity, type 2 diabetes and other metabolic disorders worldwide. Crocin is a carotenoid compound possessing various pharmacological activities. In the present study, we aimed to investigate the effect on fatty liver under diabetic and obese condition and to examine the possible role of AMP-activated protein kinase (AMPK) signaling.. db/db mice were administrated with crocin and injected with LV-shAMPK or its negative control lentivirus. Metabolic dysfunction, lipogenesis and fatty acid-oxidation in liver were evaluated.. In db/db mice, we found that oral administration of crocin significantly upregulated the phosphorylation of AMPK and downregulated the phosphorylation of mTOR in liver. Crocin reduced liver weight, serum levels of alanine aminotransferase, alanine aminotransferase, and liver triglyceride content, and attenuated morphological injury of liver in db/db mice. Crocin inhibited the mRNA expression of lipogenesis-associated genes, including sterol regulatory element binding protein-1c, peroxisome proliferator-activated receptor γ, fatty acid synthase, stearoyl-CoA desaturase 1, and diacylglycerol acyltransferase 1, and increased the mRNA expression of genes involved in the regulation of β-oxidation of fatty acids, including PPARα, acyl-CoA oxidase 1, carnitine palmitoyltransferase 1, and 3-hydroxy-3-methylglutaryl-CoA synthase 2. Moreover, treatment of crocin resulted in a amelioration of general metabolic disorder, as evidenced by decreased fasting blood glucose, reduced serum levels of insulin, triglyceride, total cholesterol, and non-esterified fatty acid, and improved glucose intolerance. Crocin-induced protective effects against fatty liver and metabolic disorder were significantly blocked by lentivirus-mediated downregulation of AMPK.. The results suggest that crocin can inhibit lipogenesis and promote β-oxidation of fatty acids through activation of AMPK, leading to improvement of fatty liver and metabolic dysfunction. Therefore, crocin may be a potential promising option for the clinical treatment for NAFLD and associated metabolic diseases.

Topics: Acyl-CoA Oxidase; Alanine Transaminase; AMP-Activated Protein Kinases; Animals; Anti-Obesity Agents; Aspartate Aminotransferases; Carnitine O-Palmitoyltransferase; Carotenoids; Diabetes Mellitus, Type 2; Diacylglycerol O-Acyltransferase; Disease Models, Animal; Fatty Acid Synthases; Gene Expression Regulation; Hydroxymethylglutaryl-CoA Synthase; Hypoglycemic Agents; Lipogenesis; Liver; Male; Mice; Mice, Transgenic; Non-alcoholic Fatty Liver Disease; PPAR alpha; PPAR gamma; Signal Transduction; Stearoyl-CoA Desaturase; Sterol Regulatory Element Binding Protein 1; Treatment Outcome; Triglycerides