Pharmacodynamic study of Ke Huang capsule in mice with nonalcoholic steatohepatitis
Objective:To explore the therapeutic effect of Ke Huang capsule on non-alcoholic steatohepatitis(NASH)mouse model induced by high-fat and high-sugar diet.Methods:A total of sixty C57/BL6 mice were randomly divided into normal group(Ctrl group),model group(HFHS group),low,medium and high dose of Ke Huang capsule groups(KL,KM and KH groups)and obeticholic acid group(OCA group).The NAFLD model was induced by high fat diet and high sugar drinking water for 12 weeks.The morphology,body weight and food intake of mice were observed.The liver weight/body weight ratio index,liver triglyceride(TG)content,HE staining and oil red O staining of liver tissue and non-alcoholic fatty liver activity score(NAS)were performed.The serum alanine aminotransferase(ALT),aspartate aminotransferase(AST)and γ-glutamyl transpeptidase(GGT)activities,serum triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)and serum free fatty acid(FFA),fasting blood glucose(FBG),fasting insulin(FINS)and insulin resistance index(HOMA-IR)were measured.Results:Compared with the Ctrl group,the mice in the HFHS group were obese,the liver was larger,the liver weight was significantly increased,the liver TG content,serum ALT and AST activities,serum TC,LDL-C,HDL-C,FINS,FBG contents and HOMA-IR were significantly increased(P<0.01),serum FFA level decreased significantly(P<0.05).The HE staining of liver tissue showed obvious hepatocyte steatosis,inflammatory cell infiltration,balloon-like changes in some hepatocytes,and a significant increase in liver tissue NAS score(P<0.01),and oil red O staining showed obvious red lipid droplets.Compared with HFHS group,TG content in liver tissue of KL,KM and KH groups decreased significantly(P<0.05);The steatosis,lobular inflammation and ballooning of liver tissue in KM,KL and KH groups were significantly reduced,and the NAS score of liver tissue was significantly decreased(P<0.05),oil red O-stained lipid droplets decreased.The serum ALT and AST activities and serum TC and HDL-C contents in KL group were significantly decreased(P<0.05),serum TG and FFA levels increased significantly(P<0.05).The levels of serum HDL-C and FBG in KM group were significantly decreased(P<0.05).KH group mice serum ALT activity,serum TC,HDL-C,LDL-C and FBG levels were significantly decreased(P<0.05).Conclusion:The low,medium and high dose groups(0.5 g/kg,1 g/kg,2 g/kg,respectively,equivalent to 6.17,12.33,24.66 times of the clinical dose)of Ke Huang capsule had different degrees of therapeutic effects on mice with non-alcoholic steatohepatitis induced by high-fat diet and high-sugar drinking water.The improvement of liver TG content has a dose-dependent trend,but the serum triglyceride and free fatty acid have an increasing effect on the capsule.