In vitro metabolism of magnolol and honokiol in rat liver microsomes and their interactions withs seven CYP 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 RLMs (rat liver microsomes) were investigated by UHPLC-Q Exactive and their possible structures were identified. In addition, 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).

CONCLUSION: This study demonstrated that different cytochrome P450 (CYP450) enzyme isoforms showed different activities in the in vitro metabolism of magnolol and honokiol and rat liver microsomes. It have a certain practical applications that we should pay attention to drugs in clinical medications - drug, drug-enzyme interactions.