Effect of honokiol on the induction of drug-metabolizing enzymes in human hepatocytes.
Honokiol, 2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol, an active component of Magnolia officinalis and Magnolia grandiflora, exerts various pharmacological activities such as antitumorigenic, antioxidative, anti-inflammatory, neurotrophic, and antithrombotic effects. To investigate whether honokiol acts as a perpetrator in drug interactions, messenger ribonucleic acid (mRNA) levels of phase I and II drug-metabolizing enzymes, including cytochrome P450 (CYP), UDP-glucuronosyltransferase (UGT), and sulfotransferase 2A1 (SULT2A1), were analyzed by real-time reverse transcription polymerase chain reaction following 48-hour honokiol exposure in three independent cryopreserved human hepatocyte cultures. Honokiol treatment at the highest concentration tested (50 μM) increased the CYP2B6 mRNA level and CYP2B6-catalyzed bupropion hydroxylase activity more than two-fold in three different hepatocyte cultures, indicating that honokiol induces CYP2B6 at higher concentrations. However, honokiol treatment (0.5-50 μM) did not significantly alter the mRNA levels of phase I enzymes (CYP1A2, CYP3A4, CYP2C8, CYP2C9, and CYP2C19) or phase II enzymes (UGT1A1, UGT1A4, UGT1A9, UGT2B7, and SULT2A1) in cryopreserved human hepatocyte cultures. CYP1A2-catalyzed phenacetin O-deethylase and CYP3A4-catalyzed midazolam 1'-hydroxylase activities were not affected by 48-hour honokiol treatment in cryopreserved human hepatocytes. These results indicate that honokiol is a weak CYP2B6 inducer and is unlikely to increase the metabolism of concomitant CYP2B6 substrates and cause pharmacokinetic-based drug interactions in humans.
College of Pharmacy, The Catholic University of Korea, Bucheon, Korea.
Yong-Yeon
YY
Cho
College of Pharmacy, The Catholic University of Korea, Bucheon, Korea.
Hyeon-Uk
HU
Jeong
Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea.
Jeong-Han
JH
Kim
College of Pharmacy, The Catholic University of Korea, Bucheon, Korea.
Hye Suk
HS
Lee
D001713:Biphenyl Compounds / Q000494:pharmacology*; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism; D000498:Allyl Compounds; D010636:Phenols
D001713:Biphenyl Compounds; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D017705:Lignans; D004364:Pharmaceutical Preparations; D012333:RNA, Messenger; D015238:Sulfotransferases; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
UDP-glucuronosyltransferases; cytochrome P450; drug interactions; honokiol; human hepatocytes