Archives of Pharmacal Research 2015-01-01

Selective induction of hepatic cytochrome P450 2B activity by leelamine in vivo, as a potent novel inducer.

JuHee Sim, Woongsik Nam, Doohyun Lee, Suyoun Lee, Hungchan O, Jeongmin Joo, Kwang-Hyeon Liu, Jae Yun Han, Sung Hwan Ki, Tae Cheon Jeong, Taeho Lee, Sangkyu Lee

Index: Arch. Pharm. Res. 38 , 725-33, (2015)

Full Text: HTML

Abstract

Cytochrome P450 (CYP) is an important enzyme that can act on xenobiotic substances such as toxic chemicals or drugs. Phenobarbital (PB) has been widely used to induce CYP2B activity to investigate the drug-drug interaction of CYP2B substrate drugs. Leelamine is a diterpene compound, and is the current focus of efforts to develop a treatment for diabetes. In this study, we identified the selective and potent inductive effect of leelamine on CYP2B at doses of 5, 10, or 20 mg/kg in male ICR mice for 1 or 3 days. In liver, the activity of CYP2B significantly increased 3.6-fold after treatment with leelamine, compared to vehicle-treated group. Activities of benzyloxyresorufin O-dealkylase and pentoxyresorufin O-dealkylase significantly increased 6.3- and 5.3-fold, respectively, with a single treatment of 20 mg/kg leelamine for 1 day. Furthermore, immunoblot analysis showed that significantly and dose-dependently increased CYP2B10 protein levels in liver. However, PCR results showed that there were no significant changes in the CAR and CYP2B mRNA levels after leelamine treatment. Accordingly, we suggest that leelamine is a novel substitute of PB for the selective induction of CYP2B activity in vivo.