Effect of honokiol on the induction of drug-metabolizing enzymes in human hepatocytes

Abstract

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.

Interleukin-2 induces the in vitro maturation of human pluripotent stem cell-derived intestinal organoids

“…Because the mature hSI plays a major role in drug absorption and metabolism and expresses a diverse array of transporters and drug-metabolizing enzymes 18 , we compared the expression patterns of various transporters and metabolizing enzymes between in vitro-matured hIOs and hSI. The main intestinal cytochrome p450 enzymes, conjugation enzymes and transporters of the solute carrier (SLC) family (uptake), and ATP-binding cassette (ABC) family (efflux) were highly expressed in hSI, as expected (Fig.…”

Identification of rifampin-regulated functional modules and related microRNAs in human hepatocytes based on the protein interaction network

“…These results also signify that rifampin can influence the anti-angiogenesis and anti-tumour effects of drugs by regulating BIRC3, CAV1, CAV2, FN1, ITGA1 and THBS1 . Previous reports support these findings, stating that UGT1A4 CYP1A1, CYP2C19, CYP2C9 and CYP2E1 are drug-metabolizing enzymes [34, 35], and ADH6 modulates the risk for drug dependence [35]. BIRC3 contains anti-apoptotic genes, which can be suppressed to counteract cancerous activity [36].…”