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

CONTEXT

Lysionotin, a major extraction of Maxim (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 μM lysionotin on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated using 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 values of 13.85, 24.95, and 30.05 μM, respectively. The inhibition of CYP3A4 was performed in a non-competitive manner with the value of 6.83 μM, while the inhibition of CYP2C19 and 2C8 was performed in a competitive manner with values of 12.41 and 14.51 μM. Moreover, it was found that the inhibition of CYP3A4 was time-dependent with / value of 6.618/0.048 min/μM. The inhibitory 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. Further experiments are needed to assess the potential interactions.