Baicalin Improves Paracetamol-induced Liver Injury And Regulates CYP2E1 Expression

Cytochrome P450 2E1(CYP2E1),a member of the CYP450 family and is responsible for the metabolism of endogenous and exogenous compounds in organisms.In addition,CYP2E1 is also involved in the occurrence and development of alcoholic liver disease,drug-induced liver injury,diabetes and other diseases.Baicalin is a kind of flavonoid compound extracted from scutellaria baicalensis,which has anti-inflammatory,antioxidant and liver protection pharmacological effects.CYP2E1 is closely related to liver diseases,and baicalin has a good protective effect on the liver.Therefore,the study on the effect of baicalin on CYP2E1 not only provides reference for the clinical use of baicalin,but also provides theoretical basis for CYP2E1 as a target for the treatment of liver diseases.Liver damage caused by paracetamol is very common,and paracetamol is an inducer of CYP2E1.Therefore,in this study,Kunming mice were used as experimental animals,and by replicating paracetamol-induced liver injury model,the increase of enzyme activity and enzyme content of CYP2E1 was induced.On this basis,baicalin was treated to investigate the protective effect of baicalin on paracetamol-induced liver injury and the influence of baicalin on the expression of CYP2E1,and its regulatory mechanism was preliminarily explored.Firstly,paracetamol was used to replicate mouse liver injury model,ALT and AST levels in serum were measured,and pathological changes of liver were observed by HE staining.CYP2E1 enzyme activity and enzyme content were determined,so as to screen the appropriate dose of paracetamol.On the basis of paracetamol induced liver injury,the serum ALT and AST levels,oxidative stress index GSH,Gsh-px,SOD,CAT and MDA levels in the liver of mice in each group were detected by the kit.The pathological changes of the liver were observed by H and E staining,and the protein expressions of Bax and Bcl-2 were determined by Western Blot.The mRNA levels of Bax and Bcl-2 were determined by q RT-PCR to confirm the protective effect of Baicalin on liver injury.The activity and content of CYP2E1 enzyme in mouse liver were determined by ELISA,the protein expressions of ERK1/2,P-ERK1/2,SP1,P-SP1 and CYP2E1 were determined by Western Blot,and the mRNA levels of SP1 and CYP2E1 were determined by q RT-PCR.To explore the mechanism of baicalin regulating the expression of CYP2E1.The experimental results showed that 300 mg/kg paracetamol could cause liver injury in mice,the serum ALT and AST levels were significantly increased(P<0.01),liver tissue showed necrosis,inflammatory cell infiltration,steatosis and other pathological changes,CYP2E1 enzyme activity and enzyme content increased(P<0.01).After baicalin treatment,the levels of ALT and AST in serum were significantly decreased(P<0.05),the levels of GSH,Gsh-Px,SOD and CAT in liver were significantly increased(P<0.05 or P<0.01),and the levels of MDA were significantly decreased(P<0.01).The protein expression ratio of Bax and Bcl-2 was significantly decreased(P<0.05 or P<0.01),the mRNA level of Bax was significantly decreased(P<0.05 or P<0.01),and the mRNA level of Bcl-2 was significantly increased(P<0.05 or P<0.01).The protective effect of baicalin on hepatic injury induced by paracetamol was determined.Then,the regulation of CYP2E1 expression by baicalin was verified.After baicalin treatment in mice with liver injury,The activity of CYP2E1 enzyme,the content of CYP2E1 enzyme,the protein expression ratio of P-ERk1/2 to ERK1/2,the protein expression of SP1,P-SP1,the protein expression of CYP2E1,the mRNA level of SP1 and CYP2E1 were significantly decreased in liver(P<0.05 or P<0.01).In conclusion,the protective effect of baicalin on liver injury induced by paracetamol is related to enhancing the antioxidant stress ability of mice and affecting the apoptosis process of liver cells.In addition,baicalin can regulate the expression of CYP2E1 through the ERK/SP1 signaling pathway,and then inhibit the activity and content of CYP2E1 enzyme.