Effect of compound Danshen Dripping Pills on rat hepatic cytochrome P450

OBJECTIVE To observe the inductive effect of compound Danshen Dripping Pills(CDDP) on main subtypes of rat hepatic cytochrome P450(CYP).METHODS Male SD rats were ig given CDDP 0.3258 g·kg-1,Radix Salviae Miltiorrhizae(RSM) 0.27 g·kg-1,Radix Notoginseng 0.0528 g·kg-1 and Borneolum Syntheticum(BS) 0.003 g·kg-1,once daily,for 28 d.Then the rat liver microsomes were cultured with probe drugs for CYP.Activities of CYP1A2,CYP2B6,CYP2C12,CYP2C13,CYP2D2 and CYP3A1 were determined by high-performance liquid chromatography-mass spectrometry(HPLC/MS/MS).The expression of cyp1a2,cyp2b1/2,cyp2c11,cyp2e1 and cyp3a1 mRNA was determined by RT-PCR.RESULTS Compared with normal control group,phenobarbitone(positive control) had inhibitory effect on the enzyme activity of CYP2D2 and CYP3A1,while the activities of CYP1A1,CYP2B6,CYP2C12 and CYP2C13 were induced(P0.05).CDDP inhibited the activity of CYP1A2 and CYP2B6,but induced CYP2D2(P0.05).RSM inhibited the activities of CYP1A2 and CYP2B6(P0.05) while Radix Notoginseng inhibited CYP1A2,CYP2B6,CYP2C13 and CYP2D2(P0.05).BS had inhibitory effect on CYP1A2,CYP2B6,CYP2C12,CYP2C13 and CYP2D2(P0.01).On the mRNA level,compared with normal control group,phenobarbitone had inductive effect on cyp1a2 and cyp2b1/2 mRNA(P0.05);CDDP,RSM and Radix Notoginseng had no significant effects on the mRNA level of cyp1a2,cyp2b1/2,cyp2c11,cyp2e1 and cyp3a1.BS significantly inhibited the mRNA level of cyp1a2,cyp2b1/2 and cyp2c11(P0.05,P0.01).CONCLUSION A single drug has more significant effect on enzymes than CDDP.BS has the most significant inhibitory effect on drug metabolic enzymes.