Abstract: This study was aimed to explore the protective effect and potential mechanism of Forsythiae suspensa extract (FSE) preventive intervention on acetaminophen (APAP)-induced liver injury in mice. The semi-bionic enzyme method was used to extract the active components of Forsythia suspense, and the mouse liver injury model was constructed by APAP in this experiment. 60 female Kunming mice were randomly divided into 6 groups:normal control(NC) group, APAP liver injury model (LD) group, Forsythia suspense extract (FSE) group, high-dose Forsythia suspense extract (HFSE+LD) group, medium-dose Forsythia suspense extract (MFSE+LD) group and low-dose Forsythia suspense extract (LFSE+LD) group. 10 mice for each group. The HFSE+LD group, the MFSE+LD group, and the LFSE+LD group were intragastrically administrated with Forsythia suspense extract 200, 100, and 50 μg/g, respectively, twice a day, for 6 consecutive days. The NC group and the LD group were given the same amount of normal saline. After preventive administration with FSE for 3 days, APAP was injected intraperitoneally once a day. Blood samples were collected from the eyeball, and the liver was quickly taken out 12 h after the last administration. Serum aminotransferase (ALT) and aspartate aminotransferase (AST) were detected to evaluate the degree of liver injury. The homogenates of liver glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA) and hydrogen peroxide (H₂O₂) were detected to evaluate the degree of liver oxidative stress of liver. Liver samples were visualized by hematoxylin and eosin staining. Furthermore, liver mitochondrial cytochrome P4502E1 (CYP2E1) activity were measured by probe drug method. The expression level of liver mitochondrial CYP2E1 mRNA was detected by Real-time quantitative PCR and the liver CYP2E1 protein expression was detected by Western blotting. The results showed that:Compared with NC group, the ALT and AST activities in serum were increased significantly (P<0.05), the SOD activity and GSH content in liver were significantly reduced (P<0.05), the MDA and H₂O₂ contents, and the expression of CYP2E1 mRNA and protein in liver were significantly increased (P<0.05) in LD group. The mouse liver injury model was successfully established. 200, 100, and 50 μg/g FSE treatment significantly reduced the serum ALT and AST activities in mice with liver injury (P<0.05), and significantly increased the liver SOD avtivity (P<0.05). 200 and 100 μg/g FSE significantly increased the GSH level in liver (P<0.05), and significantly reduced the level of MDA, H₂O₂ and the expression of CYP2E1 mRNA and CYP2E1 protein in liver (P<0.05). The results showed that FSE reduced APAP-induced mice liver injury in a manner of dose-dependent, and its potential mechanism was related to the antioxidant effect and the inhibition of CYP2E1 enzyme activity and expression of the active substances.

Key words: Forsythiae suspensa extract; acetaminophen; cytochrome P4502E1 (CYP2E1); liver injury