الفهرس 
Literature ReviewOnly 14 pages are availabe for public view
 |  | from | 131 |  |  |
| | | from | 131 | | |
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a pervasive pandemic with sequential complications including Non-alcoholic steatohepatitis (NASH) that could lead to cirrhosis and hepatocellular carcinoma (HCC). The disease comorbidities include DMII, hypertension, dyslipidemia, and gut dysbiosis. Up till now there is no FDA approved drug for treatment of NAFLD. Flavonoids such as Rhamnetin (Rhm) have been proven to be effective anti-inflammatory and anti-oxidative agent. Thus, Rhm as a potent flavonoid could target several pathological cascades causing NAFLD to prevent its progression into HCC. NAFLD is a multifactorial disease, and its pathophysiology is complex and is currently challenged by the ’Multiple-hit hypothesis’ that includes wider range of comorbidities rather than previously established theory of ’Two-hit hypothesis’. Herein, we aimed at establishing reliable in vitro NASH models using different mixtures of variable ratios and concentrations of oleic acid (OA) and palmitic acid (PA) combinations using HepG2 cell lines. Moreover, we compared those models in the context of oil red staining, triglyceride levels and their altered downstream molecular signatures for genes involved in de novo lipogenesis, inflammation, oxidative stress and apoptotic machineries as well. Lastly, the effect of Rhm on NASH and HCC models was deeply investigated. Over the 10 NASH models tested, PA 500 µM concentration was the best model to mimic the molecular map of steatosis induced NAFLD. Rhm successfully ameliorated the dysregulated molecular events caused by the PA-induced NASH. Additionally, Rhm regulated inflammatory and oxidative machinery in the HepG2 cancerous cell lines. In conclusion, PA 500 µM concentration is considered an effective in vitro model to mimic NASH. Rhm could be used as a promising therapeutic modality against both NASH and HCC pathogenesis.