OBJECTIVETo investigate the inhibitive and inductive effect of (-)-tetrahydropalmatine (THP) and (+)-THP on main CYP450 isoforms in mouse liver microsomes.

METHODSThe in vitro inhibitory effect was evaluated by incubating (-)-THP or(+)-THP with the probe substrates of main phase I metabolic enzymes in mouse liver microsomes, and the remaining substrates were determined by HPLC or LC-MS/MS method. Mice were administered with (-)-THP or(+)-THP at dosage of 240 mg/kg or 60 mg/kg by gastric lavage for successive 7 days, then the cocktail-LC-MS method was applied to assess the activities of main CYP450 isoforms in mouse liver microsomes.

RESULTThe IC(50) values of both (-)-THP and (+)-THP on isoforms studied were higher than 100 μmol/L except that IC(50) value of (+)-THP on CYP2C was 43.89 μmol/L, indicating weak inhibition of (-)-THP and (+)-THP on CYP1A2, CYP2D22, CYP2E1 and CYP3A11 in vitro. Compared with the vehicle group, the activities of CYP2D22, CYP2E1 and CYP3A11 were not increased significantly in (-)-THP and (+)-THP treatment groups, while the activities of CYP1A2 in 60 mg/kg and 240 mg/kg (-)-THP groups were 68.7% and 73.0% higher, than that of the vehicle group (P < 0.05, P < 0.01, respectively), the activity of CYP2C37 in 240 mg/kg (-)-THP treatment group was 80.4%, higher than that of the vehicle group (P < 0.05).

CONCLUSIONThere is negligible or weak inhibition on main CYP450 in mouse liver microsomes by (-)-THP and (+)-THP in vitro. (+)-THP does not induce main CYP450 in mouse liver microsomes while (-)-THP weakly induces CYP1A2 and CYP2C37.