Effect Of Xiaoyao San On Non-alcoholic Fatty Liver Disease Induced By Corticosteroids

Purposes:(1)Establishing a model of nonalcoholic fatty liver disease(nonalcoholic fatty liver disease,NAFLD)induced by Corticosteroids disorder,and evaluating XYS to reduce hepatic steatosis and lipid accumulation;(2)To explore the mechanism of Xiaoyao San in NAFLD model and the effect of saikosaponin D(Saikoside D,SSD),which provides experimental basis for Xiaoyao San to improve NAFLD.Methods:The numbers were randomly divided into C57BL/6J mice randomly divided into blank control group(ND),high fat diet group(HFD),Corticosteroids group(CORT),Xiaoyao San low dose group(XYS_L),Xiaoyao San high dose group(XYS_H),mifepristone group(RU486)and a total of 6 groups,6 in each group.The blank control group(ND)was fed with basic diet for 14 weeks,the high-fat diet group(HFD)was fed with high-fat diet for 14 weeks,and the disease model group was fed with high-fat diet for 7 weeks after loading glucocorticoid corticosterone(CORT).7 weeks of simulated emotional stress induced NAFLD model,in the process of modeling,given high and low dose of Xiaoyao San and mifepristone as a positive control for 7 weeks.The body weight and daily food intake of the mice counted;plasma triglyceride(TG),total cholesterol(T-c H),free fatty acid(FFA),liver triglyceride(TG),total cholesterol(T-c H)and long Chain acyl-Co A dehydrogenase(LCAD)activity were measured.liver histological morphology,Perili-pin family genes filter,Western blotting was used to detect the expression of ADFP,GR and FKBP51 in liver tissue.Detection of ADFP recruitment by extraction and Separation of Lipid droplets from liver tissue.The mechanism of SSD on NAFLD was verified by cell experiment in vitro.Results:After 7 weeks of XYS group intervention,the levels of TC,TG,FFA in plasma and TG in liver tissue decreased significantly,which reversed the activity of LCAD.The results of HE staining and oil red O staining showed that the morphology of hepatocytes was near normal,a few vesicular lipid droplets were found,and lipid accumulation was decreased.Further studies on the mechanism showed that the expression of GR protein and the inhibition of translocation into nuclei decreased the expression of ADFP gene and protein,and decreased the protective effect of ADFP on lipid droplets.At the same time,it promoted the maintenance of energy balance activity of AMPK and inhibited the phosphorylation of AMPK to promote the phosphorylation of ADFP and the decomposition of lipid droplets by lipase.In vitro,the main effective components of the effective active ingredient,saikosaponin D,are consistent with the improvement of the pharmacological action of the NAFLD in the in vivo experiment.Conclusion:(1)XYS has intervention effect on NAFLD animal model induced by corticosteroids with disorder.(2)XYS inhibited the expression of GR and nuclear translocation activity,reduced the expression and recruitment of ADFP,and inhibited the growth of lipid droplets.At the same time,XYS enhanced the activity of AMPK to inhibit the phosphorylation of AMPK,increase the activity of LCAD,promote the decomposition of lipids and improve the growth of NAFLD.(3)The main component of XYS in NAFLD may be saikosaponin D(SSD).