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In vitro metabolism of magnolol and honokiol in rat liver microsomes and their interactions with seven cytochrome P substrates.

RATIONALE
Magnolol and honokiol are the main active components of Magnolia officinalis Rehd. et Wils. The study of their interactions with liver microsomes is very important for the clinical safety of M. officinalis Rehd. et Wils.


METHODS
The main metabolites of magnolol and honokiol in rat liver microsomes were investigated using ultrahigh-performance liquid chromatography/mass spectrometry and their possible structures were identified. In addition, cytochrome P450 (CYP450) isoenzymes of the major rat metabolites of magnolol and honokiol were identified using a specific inhibitor.


RESULTS
This study suggests that the CYP2E1 subtype is responsible for the oxidation of magnolol and honokiol terminal double bonds to epoxy metabolites. CYP3A4 appears to be the major subtype responsible for further hydrolytic metabolism, while CYP1A2 may promote decarboxylation of the metabolites. CYP2A6 may be the main subtype responsible for the hydrogenation of magnolol (p < 0.05).


CONCLUSIONS
This study demonstrated that different CYP450 enzyme isoforms showed different activities in the in vitro metabolism of magnolol and honokiol in rat liver microsomes. It has certain practical applications in that we should pay attention to drug-drug interactions in clinical medications and also to drug-enzyme interactions.