Abstract:

This study aims to investigate the effect of gypenosides (GPs) on nonalcoholic fatty liver disease (NAFLD) by improving liver lipid deposition,and to explore its potential mechanism.Twelve ApoE-/- mice were randomly divided into model group (Mod) and gypenosides group(GPs),and six C57BL/6J mice were used as blank control (Con) group.Con group was fed with normal diet,and the other groups were fed with high-fat diet for 12 weeks.GPs group was given 2.97 g/(kg·d) by gavage,and Con group and the Mod group were given the same volume of normal saline by gavage for 4 weeks.The levels of triglyceride (TG),total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),high-density lipoprotein cholesterol (HDL-C) level in mice serum were detected by fully automated biochemical analyzer,hematoxylin-eosin (HE) staining to observe the mice liver pathological morphology,oil red O staining to observe the mice liver lipid deposition,the contents of TG and free fatty acid (FFA) in liver were detected by ELISA.The mRNA and protein expression squalene cyclooxygenase (SQLE),carbonic anhydrase Ⅲ (CA3),sterol regulatory factor binding protein-1c (SREBP1c),acetyl-coa carboxylase (ACC),fatty acid synthase (FASN),stearoyl-CoA desaturase 1 (SCD1) in liver were detected by real-time PCR and Western blot.The results showed that compared with Con,the levels of TC,TG and LDL-C in Mod group were significantly increased,and the level of HDL-C was significantly decreased (P<0.01).There were a large number of fat vacuoles in hepatocytes,and the liver lipid deposition was obvious;the contents of TG and FFA increased (P<0.01).SQLE,CA3,SREBP1c,ACC,FASN,SCD1 protein and mRNA expression increased (P < 0.05 or P < 0.01).Compared with Mod,TG,TC,LDL-C were significantly reduced and HDL-C were significantly increased in GPs group (P<0.01);the morphology of hepatocytes tended to be normal and lipid droplets decreased,liver lipid deposition loss;TG and FFA content decreased significantly (P<0.01);SQLE,CA3,SREBP1c,ACC,FASN and SCD1 proteins and mRNA expression decreased (P < 0.05 or P<0.01).In conclusion,gypenosides can inhibit fatty acid synthesis and reduce lipid accumulation through SQLE/CA3/SREBP1C pathway,thereby improving NAFLD.

Key words: gypenosides, SQLE-CA3 axis, fatty acid synthesis, lipid deposition in liver, nonalcoholic fatty liver disease