Taxifolin Alleviates Non-alcoholic Fatty Liver With Acute Alcohol Stimulation Via Regulating NLRP3 Inflammasome

OBJECTIVE Taxifolin(TAX)is a dihydroflavanols compound with high content in artichoke,larch and fir.In this study,the intervention mechanism of taxanthophyllin on liver fat accumulation and inflammation was investigated by establishing a high-fat model of in vivo high-fat feed feeding combined with acute alcohol gavage and in vitro cell-stimulated lipid accumulation.METHODS 1.In vivo experiments of non-alcoholic fatty liver mice with acute alcohol stimulation:normal group and single drug administration group were fed normal solid diet;The high-fat group was fed with high-fat diet.The single dose group was given taxocyanin at a dose of 25mg/kg body weight.The alcohol group was given 31.25%alcohol;The low,medium and high dose groups were given taxocyanin and 31.25%alcohol at 1mg/kg,5mg/kg and 25mg/kg body weight,respectively.The control group was given metformin at dose 300mg/kg and 31.25%alcohol.In the first 8 weeks,the mice were fed normal diet,high-fat diet,free drinking water,weighed and fed daily.From the 9th week,in addition to group feeding,each group was given corresponding concentrations of drugs(TAX,metformin)by intragastric administration every day according to the group,and the weight and food intake of mice were recorded every day.The night before the death of the mice were free to drink water but fasting.At the end of the morning of the day of the execution,the drug was administered orally with alcohol.The contents of ALT,AST,TG,TC,HDL-C and LDL-C were detected with the corresponding kit.HE staining and immunohistochemical staining were used to observe the effects of TAX on the changes of liver histomorphology in mice.2.In vitro experiment of non-alcoholic fatty liver:HepG2 cells were selected for stimulation modeling:after HepG2 cells were given different concentrations of TAX(25,50,100,200 μM),oleic acid(OA,2mM)stimulation for 18h and palmitic acid(PA,500 μM)stimulation for 12h,a series of changes were induced in liver cells.After successful modeling,proteins were extracted for western blot test to detect the expressions of srebp-1 and P2x7R,and the expressions of srebp-1 and caspase-1 were observed by immunofluorescence staining and the morphological changes of liver cells were observed by oil red staining.RESULTS:Combined high fat diets with alcohol binge in mice liver injury model,taxifolin in serum ALT,AST,TC,TG,LDL-C,HDL-C and significant inhibiting effect on the level of TG in the liver than the positive control group statistically significant and obvious effect,HE,oil liver tissue pathology,such as red,immunohistochemical staining showed that taxifolin have a certain degree of relief to nonalcoholic fatty liver disease have a certain degree of relief.2.In vitro experimental results showed that TAX significantly inhibited the expression of srebp-1,P2X7R and caspase-1 in liver cells induced by OA and PA.CONCLUSION In this study,it was proved that high fat diet could form fat accumulation,and the fat accumulation caused by high fat diet combined with alcohol acute gavage was more obvious.The results showed that taxifolin could improve and reverse the fat accumulation caused by high-fat diet,and it could inhibit the inflammation associated with fatty liver and protect the liver to some extent.