Abstract
Honokiol (2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol) and magnolol (4-Allyl-2-(5-allyl-2-hydroxy-phenyl)phenol) are the major active polyphenol constituents of Magnolia officinalis (Magnoliaceae) bark, which has been widely used in traditional Chinese medicine (Houpu Tang) for the treatment of various diseases, including anxiety, stress, gastrointestinal disorders, infection, and asthma. The aim of this study was to investigate the direct effects of honokiol and magnolol on hepatic CYP1A and 2C-mediated metabolism in vitro using rat liver microsomes and in vivo using the Sprague-Dawley rat model. Honokiol and magnolol inhibited in vitro CYP1A activity (probe substrate: phenacetin) more potently than CYP2C activity (probe substrate: diclofenac): The mean IC50 values of honokiol for the metabolism of phenacetin and diclofenac were 8.59 μM and 44.7 μM, while those of magnolol were 19.0 μM and 47.3 μM, respectively. Notably, the systemic exposure (AUC and Cmax) of phenacetin, but not of diclofenac, was markedly enhanced by the concurrent administration of intravenous honokiol or magnolol. The differential effects of the two phytochemicals on phenacetin and diclofenac in vivo pharmacokinetics could at least be partly attributed to their lower IC50 values for the inhibition of phenacetin metabolism than for diclofenac metabolism. In addition, the systemic exposure, CL, and Vss of honokiol and magnolol tended to be similar between the rat groups receiving phenacetin and diclofenac. These findings improve our understanding of CYP-mediated drug interactions with M. officinalis and its active constituents.
Highlights
The past two decades have seen a significant increase in the utilization of herbal extract formulations to complement prescription drugs administered for the prevention and treatment of disease [1]
The present study provides novel data on the pharmacokinetic interactions of honokiol and magnolol with the CYP1A and 2C substrate drugs, phenacetin and diclofenac, in the SD rat model
The present study demonstrates that honokiol and magnolol inhibit CYP1A activity more potently than CYP2C activity in vitro
Summary
The past two decades have seen a significant increase in the utilization of herbal extract formulations to complement prescription drugs administered for the prevention and treatment of disease [1]. Safer, than prescription drugs [4].drugs. /or misconceptionthat thatherbs herbs safer, than prescription [4]. Herbal extract products contain various active phytochemicals, some of which are cleared by the herbal extract products contain various active phytochemicals, some of which are cleared cytochrome P450 (CYP). Isozymes responsible for the metabolism of most prescription drugs [5]. By the cytochrome P450 (CYP) isozymes responsible for the metabolism of most prescription drugs. CYP-based herb-drugherb-drug interactions are inevitable, yet the CYP-modulating potential and the associated Patients mainly tendto toconsume consumeherbal herbalmedicine medicineowing owingtotodissatisfaction dissatisfactionwith withthe theefficacy efficacyofofprescription prescriptiondrugs, drugs, tend and/orthe the misconception areare ‘natural’
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
