Evaluation of Honokiol, a Major Component of Magnolia officinalis, as an Inhibitor on Human Cytochrome P450 Enzymes in vitro

Abstract

Magnolia bark has been the focus of attention in the research community owing to its worldwide usage for various clinical disorders, such as gastrointestinal disorder, anxiety and allergies. Despite its extensive use, only a few studies regarding the possible interactions of the magnolia plant s components with medicines have been reported. In this study, an incubation experiment with pooled human liver microsome (HLM) was performed to elucidate the mechanism underlying the effects of honokiol, a major ingredient of Magnolia officinalis, on human cytochrome P450 (CYP) isoenzymes. CYP isoenzyme specific substrates were incubated with multiple concentrations of honokiol, HLM and NADPH regenerating systems. For the estimation of the inhibition constant (K i ) and mode of inhibition, incubation studies with various concentrations of each CYP isoenzyme specific probe were performed. Honokiol demonstrated potent inhibitory effects on CYP1A2, CYP2C9, CYP2C19 and CYP2D6 with IC 50 values of 3.73, 4.91, 3.71 and 20.27μM, respectively. Honokiol inhibited CYP1A2, CYP2C9 and CYP2C19 with a competitive mode, exhibiting K i values of 1.62, 4.73 and 2.19 μM, respectively. In contrast, the inhibition of CYP2D6 by honokiol was explained by an uncompetitive inhibition mode with a K i value of 14.34 μM. These findings suggest that honokiol could have inhibitory effects on the metabolic activity mediated by CYP1A2, CYP2C9, CYP2C19 and CYP2D6 in humans.