title: [Inhibitory and inductive effects of (-)- and (+)-tetrahydropalmatine on CYP450 in mice].
abstract: To investigate the inhibitive and inductive effect of (-)-tetrahydropalmatine (THP) and (+)-THP on main CYP450 isoforms in mouse liver microsomes.
  
  
  
  The 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.
  
  
  
  The 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).
  
  
  
  There 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.
authors.affiliation: Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Science, Zhejiang University, Hangzhou 310058, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Li-ping
authors.initials: LP
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Shen
authors.forename: Hui-di
authors.initials: HD
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001600:Berberine Alkaloids / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*
chemical_list: D001600:Berberine Alkaloids; C014215:tetrahydropalmatine; D003577:Cytochrome P-450 Enzyme System