Effect of total saikosaponins on the intestinal first-pass effect and liver Cyp3a, Cyp2e1

Abstract

Abstract: AIM: To investigate the effect of total saikosaponins on intestinal first-pass effect (Cyp3a, P-glycoprotein) and Cytochrome P450 (Cyp3a, Cyp2e1).METHODS: The mice of each group were treated with water or investigated samples at two times a day for three days. The concentration of acetaminophen was determined by spectrophotometer. Liver/intestinal microsomes were separated by ultracentrifugation. The activity of Cyp3a and Cyp2e1 was detected by spectrophotometry. The expression of Cyp3a11/Cyp2e1 mRNA in liver was estimated by real-time PCR.RESULTS: Blood APAP concentration and P-glycoprotein coupled ATPase activities were no significant differences between all saikosaponin groups and control group (P>0.05); Cyp3a activities of high-dosage group (150 mg/kg) both in liver and intestinal microsomes, erythromycin and aminopyrine as the substrate, was significantly higher than that of control group (P<0.05) in both intestine and liver, Cyp2e1 activity of liver microsomes in high-dosage group (150 mg/kg) was significantly lower than that of control group (P<0.05); RT-PCR results indicate that only high doses of saikosaponins (150 mg/kg) can induce the expression of Cyp3a11 in the liver.CONCLUSION: Total saikosaponins can induce CYP3A4 activity in mouse liver and intestine, while inhibit Cyp2e1 activity in mouse liver and have no influence on P-glycoprotein efflux activity when large dosage was administrated.

Key words: Saikosaponins, Cyp3a11, Cyp2e1, P-glycoprotein, mRNA expression

CLC Number:

R965.2

WANG Yong-hui, QI Jin-feng, LIN Mei. Effect of total saikosaponins on the intestinal first-pass effect and liver Cyp3a, Cyp2e1[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(7): 740-748.

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