Investigation of the effects of selonsertib and phenolic acids in an In Vitro model of hepatic steatosis

Non-alcoholic fatty liver disease is a serious health problem that threatens approximately half of the adult population worldwide. The disease starts with liver fat accumulation and can progress to cirrhosis, a severe condition. Although its pathogenesis is not yet fully understood, the risk factors associated with the disease are quite evident. These include insulin resistance, unhealthy lifestyle, and obesity. Despite ongoing drug trials, there is no definitive medication currently available. In this thesis, an in vitro non-alcoholic fatty liver disease model was studied using the HepG-2 cell line and induced with oleic acid. To prevent liver fat accumulation, the cytotoxic effects of Selonsertib, Fenofibrate, Ferulic acid, Caffeic acid, and Vanillic acid were measured using the MTT method in the created fat accumulation model, and their IC50 values were calculated. The apoptotic effects of the drugs and phenolic acids were measured by the Annexin V-PI method at non-toxic concentrations, and intracellular and extracellular cytokine levels were also measured by flow cytometry. According to the analysis results, Ferulic acid was the most effective in reducing the apoptotic effect in the created in vitro fatty liver model. The termination of Phase III studies for Selonsertib as a drug for non-alcoholic fatty liver disease was found to be consistent with the experimental results obtained in this thesis. Caffeic acid was found to inhibit the levels of IL-6 and TNF-α in the fatty liver model. The substances that improved the IL-10 level according to the fatty liver model were Fenofibrate, Ferulic acid, Caffeic acid, Selonsertib, and Vanillic acid. The use of Ferulic acid, in particular, alongside medications in non-alcoholic fatty liver disease, could be promising in terms of the potential emergence of new combined preparations.