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Modulation of Rat Hepatic CYP1A and 2C Activity by Honokiol and Magnolol: Differential Effects on Phenacetin and Diclofenac Pharmacokinetics In Vivo

Authors :
In-Soo Yoon
Sangbum Kim
Heon-Min Ryu
Dae-Duk Kim
Kyu-Sang Kim
Jin Woo Park
Seong-Ho Hong
Bo-Kyoung Kim
Source :
Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry, Molecules, Vol 23, Iss 6, p 1470 (2018), Molecules, Volume 23, Issue 6
Publication Year :
2018

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 &mu<br />M and 44.7 &mu<br />M, while those of magnolol were 19.0 &mu<br />M and 47.3 &mu<br />M, 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.

Details

ISSN :
14203049
Volume :
23
Issue :
6
Database :
OpenAIRE
Journal :
Molecules (Basel, Switzerland)
Accession number :
edsair.doi.dedup.....264f69d4a981016b4801d1b53fb80471