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Molecules 2018, 23(6), 1470;

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

New Drug Development Center, Daegu‒Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea
Biomedicine Lab, CKD Research Institute, Gyeonggi 16995, Korea
Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 58554, Korea
Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Korea
Authors to whom correspondence should be addressed.
Received: 24 April 2018 / Revised: 6 June 2018 / Accepted: 16 June 2018 / Published: 17 June 2018
(This article belongs to the Section Natural Products Chemistry)
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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. View Full-Text
Keywords: honokiol; magnolol; Magnolia officinalis; CYP1A; CYP2C; rat; pharmacokinetics honokiol; magnolol; Magnolia officinalis; CYP1A; CYP2C; rat; pharmacokinetics

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Kim, S.-B.; Kim, K.-S.; Ryu, H.-M.; Hong, S.-H.; Kim, B.-K.; Kim, D.-D.; Park, J.W.; Yoon, I.-S. Modulation of Rat Hepatic CYP1A and 2C Activity by Honokiol and Magnolol: Differential Effects on Phenacetin and Diclofenac Pharmacokinetics In Vivo. Molecules 2018, 23, 1470.

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