Effects of imperatorin and isoimperatorin on liver cytochrome P450s in mice / 中成药

ABSTRACT

AIM To investigate the effects of imperatorin and isoimperatorin on the expression of mouse liver cytochrome P450s and hepatic toxicity in mice.METHODS C57BL/6 mice were randomly divided into control and administration groups,which were treated with imperatorin or isoimperatorin by intragastric administration for two weeks.The effects of two compounds on mRNA expressions of major P450s isoforms were analyzed by RT-PCR.The P450 expression was determined by Western blot.The serum levels of glutamicpyruvic transaminase (GPT),glutamic-oxalacetic transaminase (GOT) and blood total bilirubin (TBIL) were detected by kits.The change of liver tissue was observed with HE staining.RESULTS The Cyp1a2 mRNA expression was significantly induced by 40 mg/kg imperatorin as compared with the control group.For isoimperatorin,the Cyp2c37 mRNA expression was significantly induced.Western blot results showed that CYP1 A2 expression was significantly induced by imperatorin.For isoimperatorin,the CYP2C and CYP2E1 expressions were significantly induced.Blood biochemical indices showed that 40 mg/kg isoimperatorin led to increased serum GOT and TBIL levels.Pathological analysis showed that both compounds (at the doses of 20 mg/kg and 40 mg/kg) could cause liver edema to a certain degree.CONCLUSION Imperatorin is the inducer of CYP1A2,while isoimperatorin is the inducer of CYP2C and CYP2E1.These two compounds (at the doses of 20 mg/kg and 40 mg/kg) can lead to damage for mouse liver.The toxicity of isoimperatorin is stronger than that of imperatorin.