In vitro inhibitory effect of lysionotin on the activity of cytochrome P450 enzymes.

Context Lysionotin, a major extraction ofLysionotus pauciflorusMaxim (Gesneriaceae), has a variety of pharmacological properties commonly used in the treatment of lung disease. A study of lysionotin on the activity of human liver cytochrome P450 (CYP) enzymes can provide guidance on the clinical application of lysionotin. Objective This study investigated the interaction between lysionotin and CYPs. Material and method The effects of 100 mu M lysionotin on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigatedin vitrousing human liver microsomes (HLMs) with specific inhibitor as positive control and untreated HLMs as control. Meanwhile, the enzyme kinetic parameters were calculated. A time-dependent study was performed with a time interval of 5 min in 30 min. Results Lysionotin was found to inhibit the activity of CYP3A4, 2C19, and 2C8, with IC(50)values of 13.85, 24.95, and 30.05 mu M, respectively. The inhibition of CYP3A4 was performed in a non-competitive manner with theKivalue of 6.83 mu M, while the inhibition of CYP2C19 and 2C8 was performed in a competitive manner withKivalues of 12.41 and 14.51 mu M. Moreover, it was found that the inhibition of CYP3A4 was time-dependent withK(I)/K(inact)value of 6.618/0.048 min/mu M. Discussion and conclusions:Thein vitroinhibitory effect of lysionotin on the activity of CYP3A4, 2C19, and 2C8 indicated potential drug interactions between lysionotin and drugs metabolised by CYP3A4, 2C19, and 2C8. Furtherin vivoexperiments are needed to assess the potential interactions.