Mechanism of Geniposide on Non-alcoholic Steatohepatitis Rats Based on Protein Ubiquitination
Objective To observe the effect of Geniposide on non-alcoholic steatohepatitis(NASH)rats,and to explore its mechanism based on protein ubiquitination.Methods NASH rat model was established by high-fat diet for 16 weeks.Thirty two rats were randomly divided into normal group,model group,Geniposid group and Pioglitazone hydrochloride group,with 8 rats in each group.The drug was administered at the 9th week,rats in normal group and model group were given 10 mL·kg-1·d-1 double distilled water by gavage,while those in Geniposide group and Pioglitazone hydrochloride group were respectively given 60 mg·kg-1·d-1 geniposide solution and 10 mg·kg-1·d-1 Pioglitazone hydrochloride solution,for a total of 8 weeks of intervention.The level of triglyceride(TG)in liver tissue and the contents of total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)in serum were detected by biochemical method.HE staining was used to observe the pathological changes of liver tissue.The activities of Ubquitin-specific protease 18(USP18),transforming growth factor-β activated kinase-1(TAK1)and TGF-beta-activated kinase 1 and MAP3 K7-binding protein 1(TAB1)were detected by ELISA.Results Compared with the normal group,typical histological characteristics of NASH was showed in the model group.After intervention,the steatosis and inflammatory infiltration of hepatocytes were reduced compared with the model group.Compared with the normal group,the weight,fat weight,liver wet weight,liver index,and TG content in the model group increased(P<0.05),while the protein expression of USP18,TAK1 and TAB1 in liver tissue decreased(P<0.05).Compared with the model group,the fat weight,liver wet weight,liver index,TG content in liver tissue,serum TC and LDL-C content decreased,while the protein expression of USP18,TAK1 and TAB1 in liver tissue significantly increased in Geniposide group(P<0.05).The fat weight,liver index,TG content in liver tissue,serum TC and LDL-C content decreased in Pioglitazone hydrochloride group(P<0.05).Conclusion Geniposide could improve the steatosis and inflammation of rat liver tissue,and increase the levels of USP18,TAK1 and TAB1 in rat liver tissue,and its mechanism might be related to the regulation of protein ubiquitination.
Geniposidenon-alcoholic steatohepatitisprotein ubiquitinationChinese medicine monomers