Coumarin Compounds Against Nonalcoholic Fatty Liver Activity In Vitro Screening

Due to lifestyle changes and dietary changes,the Nonalcoholic fatty liver disease(NAFLD)is a growing metabolic syndrome in China.Patients with no history of excessive drinking,pathological features of liver cell steatosis,oxidative damage and sugar intake decreased.NAFLD early manifested as simple fatty liver,non-alcoholic steatohepaitis(NASH),late may develop into fatty liver fibrosis and cirrhosis,and even liver cancer.NAFLD is a manifestation of liver metabolic problems,and its current research has been focused on the pathogenesis and prevention measures.Studies have shown that the pathogenesis of NAFLD is very complex and controlled by a variety of factors,which needed for long-term treatment.Therefore,in recent years,the prevention and treatment of NAFLD drugs mainly from the natural products to find good efficacy,side effects of small compounds.At present,there is no special drug treatment of NAFLD.As a class of important chemical composition of traditional Chinese medicine,coumarin compounds have good antioxidant activity,can regulate the liver glycolipid metabolism,reduce liver cell lipid accumulation.It is suggested that coumarin compounds may have the potential to improve the lipid accumulation,oxidative damage and hepatic fibrosis of liver tissue caused by non-alcoholic steatohepatitis.Therefore,seven simple coumarin compounds are selected from coumarin compounds as the target compound screened for non-alcoholic fatty liver drugs.HepG2 cells were induced by oleic acid as an vitro model of non-alcoholic fatty liver cells.The model cells were treated with six simple coumarin compounds to detect intracellular TG content,ROS content and uptake of fluorescent glucose.The results showed that the three compounds of daphnetin,scoparone and esculetin could improve the NAFLD model cells.It could decrease the TG content of NAFLD cells and reduce the accumulation of cell lipid.It also promoted the uptake of glucose and improvedthe insulin resistance of NAFLD model cells Cell.It also reduce the ROS content of NAFLD model cells,reducingthe oxidative damage of NAFLD model cells.The compounds were further screened for the further study of daphnetin,scoparone and esculetin.The model cells were treated with daphnetin,scoparone and esculetin respectively.The effects of the drug on the NAFLD cells were detected by selecting the dose of different medium and three different administration time points.The results showed that the improvement of the NAFLD model cells was enhanced with the increase of the administration concentration,and showed a dose-dependent effect.However,with the increase of dosing time,the effect of daphnetin,scoparone and esculetin on NAFLD cells was not obvious.In summary,in lipid-lowering,the performance of esculetin was better than daphnetin and scoparone;In the reduction of oxidative damage,the performance of daphnetin was stronger than that of scoparone and esculetin.In the aspect of promoting sugar uptake,the performance of daphnetin was stronger than that of scoparone and esculetin.In conclusion,the two coumarin compounds of daphnetin and esculetin are superior to the scoparone in improving the lipid accumulation,oxidative damage and sugar uptake of NAFLD model cells.Daphnetin and esculetin may be a potential drug for NAFLD.The molecular mechanism of their treatment needs further study.