Dihydroquercetin Alleviates Alcoholic Fatty Liver And Inflammation Via Inhibition Of NLRP3 Inflammasome

OBJECTIVE Dihydroquercetin is a flavonoid compound.According to preliminary studies found that dihydroquercetin has a strong antioxidant effect,with high potential.In this study,we investigated whether dihydroquercetin could inhibit the accumulation of fat in alcoholic liver injury mice by using binge drinking alcoholic liver injury model and acute alcoholic liver injury model.METHODS 1.Binge drinking Alcoholic Liver Injury in Mice Model:Administration of low,medium and high dose groups were given different concentrations of dihydroquercetin(1mg/kg?5mg/kg?25mg/kg)daily for 5 days.The fifth day of intragastric administration every half an hour for a total of 3 doses.All mice were sacrificed 4 h after the last dosing.The liver histomorphological changes were observed by HE staining and Oil Red O staining.2.Acute alcoholic liver injury in Mice Model:Mice were intragastrically treated with ethanol(5 g/kg,body weight)every 12 hours for a total of 3 doses.Normal mice received an isocalorical maltose solution,and dihydroquercetin was gavaged simultaneously with ethanol to the mice in ethanol plus dihydroquercetin groups.All mice were sacrificed 4 h after the last dosing.The liver protective effect of TAX was observed by HE staining and immunohistochemistry.The expression of factors related with lipid synthesis and oxidation such as SREBP-1,ACC,AMPK and LKB1 and the factors related with fibrosis observed by Western blot and immunohistochemistry.3.Acute alcoholic liver injury in vitro:HepG2 cells were treated with different concentrations of dihydroquercetin.The expression of AMPKa,ACC and IL-10 was detected by immunohistochemistry after 24 hours.RESULTS 1.Binge drinking Alcoholic Liver Injury in Mice Model:In the model of alcoholic liver injury,the content of TG in serum and liver tissue decreased and the contents of ALT and AST in serum decreased by dihydroquercetin group.HE staining and immunohistochemistry showed that dihydroquercetin can significantly reduce alcohol-induced liver steatosis.2.Acute alcoholic liver injury in mice model,dihydroquercetin group can significantly reduce the serum TG and liver tissue TG content,reduce serum ALT,AST content;HE staining and immunohistochemical results show that dihydro quercetin can significantly reduce alcohol-induced liver fat degeneration;dihydroquercetin significantly reduced P2x7R,Caspase-1 and NLRP3 inflammatory body positive expression,reduce the macrophages and neutrophils inflammatory recruitment.At the same time,dihydroquercetin can activate AMPKa,SIRT-1,inhibit the expression of ACC and SREBP-1.3.In vitro,dihydroquercetin also inhibited the expression of ACC and IL-1? in alcohol-induced hepatocytes,and activated AMPKa and LKB1CONCLUSION This study shows that dihydroquercetin has a protective effect on liver fat accumulation occurred in binge drinking alcoholic liver injury and acute alcoholic liver injury in mice,meanwhile also have a certain inhibitory effect on the liver associated with inflammation...