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

Title
Selective induction of hepatic cytochrome P450 2B activity by leelamine in vivo, as a potent novel inducer
Author(s)
정태천심주희[심주희]남웅식[남웅식]이두현[이두현]이수연[이수연]오흥찬[오흥찬]주정민[주정민]류광현[류광현]한재윤[한재윤]기성환[기성환]이태호[이태호]이상규[이상규]
Keywords
UDP-GLUCURONOSYLTRANSFERASES; SUBSTRATE-SPECIFICITY; RECEPTOR CAR; CYP2B GENE; METABOLISM; LIVER; GLUCURONIDATION; INHIBITORS; ACID; RAT
Issue Date
201505
Publisher
PHARMACEUTICAL SOC KOREA
Citation
ARCHIVES OF PHARMACAL RESEARCH, v.38, no.5, pp.725 - 733
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.
URI
http://hdl.handle.net/YU.REPOSITORY/32280http://dx.doi.org/10.1007/s12272-014-0443-0
ISSN
0253-6269
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약학대학 > 약학부 > Articles
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