Effects of berberine hydrochloride and coadministration with cyclosporine A on liver microsomal cytochrome P450 isoenzyme in mice

OBJECTIVE: To study the effects of berberine hydrochloride(BBH) and coadministration with cyclosporine A(CsA) on liver microsomal cytochrome P450 isoenzyme in mice. METHODS: The activity of liver microsomal erythromycin N-demethylase (ERD) and aminopyrence N-demethylase(ADM) were determined by spectrophotography before and after treatment with BBH, CsA and two drug coadministration respectively. The levels of mRNA expression of CYP3A1, CYP1A1 and CYP2E1 were assayed with RT-PCR. RESULTS BBH at 200 mg&middotkg-1 had no significant inhibitory effect on ERD, but it exhibited the inhibitory action on ADM after oral administration of BBH for 3 or 6 days in mice. CsA at 45 mg&middotkg-1 markedly inhibited the activities of ERD and ADM. ERD and ADM were both inhibited by coadministration of BBH and CsA. The mRNA expression of CYP3A1 and CYP2E1 were found to be decreased markedly following exposure to the coadministration of BBH and CsA. CONCLUSION: The combination of BBH and CsA appeared to be a powerful inhibitor on ERD(CYP3A1), ADM and CYP2E1.