Effect of ginsenoside Rg1 against non-alcoholic fatty liver disease in mice and its mechanism

Abstract:

Objective：To investigate the effect of ginsenoside Rg1 on non-alcoholic fatty liver disease（NAFLD） in mice induced by high fat diet and its possible mechanism. Methods：A total of 42 healthy female adult C57/BL mice were randomly divided into the control group，model group，Rg1 low dose group，Rg1 high dose group，and metformin group，with 9 mice in each of the previous two groups and 8 in each of the latter. The control group was fed with the normal diet，while the others were fed with the high fat diet，and the feeding was continued for 16 weeks. Then the mice were treated with gastric perfusion，among them，the control group and the model group were treated with normal saline 20 mL（kg·d），Rg1 low dose group with Rg1 20 mg/（kg·d），Rg1 high dose group with Rg1 40 mg/（kg·d），and metformin group with Rg1 150 mg/（kg·d）. After 4 weeks of treatment，the serum and liver tissues of each group were collected. The pathological morphology of liver tissue was observed. The serum transaminase，lipid levels，the content of malondialdehyde（MDA），superoxide dismutase（SOD），free fatty acids（FFA） and the expression of endoplasmic reticulum stress（ERS） related proteins and inflammasome were measured. Results：In Rg1 low dose group and high dose group，the levels of serum alanine aminotransferase（ALT） were （41.87±10.64） and（43.46±13.84） U/L，the levels of aspartate aminotransferase（AST） were （159.56±21.29） and （159.56±25.01） U/L，and the levels of triglycerides（TG） were （0.69±0.15） and （0.75±0.12） U/L respectively，all of which were significantly lower than those in the model group（P=0.001，P=0.010，P=0.000）. And the fatty degeneration degree of liver tissue in the two groups was also significantly smaller than that in the model group（P=0.000）. Rg1 could reduce the contents of FFA and MDA，increase the vitality of SOD（all P=0.000），and down-regulate the expressions of GRP78，CHOP，Caspase12，NLRP3 and IL-1β（P=0.000，P=0.003）. Rg1 can also reduce the expres－sion of endoplasmic reticulum stress related proteins and in－flammasome activation（P=0.000，P=0.003）. Conclusion：Rg1 may improve NAFLD by improving the activity of antioxidant en－zymes and inhibiting the endoplasmic reticulum stress and in－flammasome activation.