Modulation of activities and mRNA expression of cytochrome P450 isoenzymes in rat liver by Sophora flaveacens and coadministration with Veratrum nigrum

Objective: To study the modulatory effect of Sophora flaveacens and co-administration with Veratrum nigrum on the activity and mRNA expression of cytochrome P450 isoenzymes in rat liver. Method: Rat liver microsomal cytochrome P450, b5, aminopyrine N-demethylase (APND), p-nitrophenol-hydroxylase (pNPH) activities were quantitated by UV chromatography. The mRNA expression level of five CYP isoenzymes CYP1A1, CYP2B1/2, CYP2C11, CYP2E1 and CYP3A1 were detected by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Result: S. flaveacen and its combination with V. nigrum can dramatically reduce P450 and b5 protein content. Both single and combined use inhibited the activities of aminopyrine N-demethylase. At the mRNA level, the expression of CYP2C11 markedly induced exposure to V. nigrum, while decreased after combination with S. flaveacens. S. flaveacens can induce CYP2B1/2 gene expression, while the Sophora- Veratrum group showed weak inhibition. Both single and co-administrated group have some inhibitory effect on CYP3A1 gene expression, while CYP1A gene expression almost has no change in each group. Conclusion: These results indicated that compatibility of Sophora and Veratrum in a prescription also have herb-herb interactions based on P450. The possible mechanisms of its incompatible effects need to be further analysised via integrating with metabolic studies.