Inhibitory effects of the essential oil of chamomile (Matricaria recutita L.) and its major constituents on human cytochrome P450 enzymes.
Chamomile extracts and tea are widely used herbal preparations for the treatment of minor illnesses (e.g. indigestion, inflammation). In this study the inhibitory effect of chamomile essential oil and its major constituents on four selected human cytochrome P450 enzymes (CYP1A2, CYP2C9, CYP2D6 and CYP3A4) was investigated. Increasing concentrations of the test compounds were incubated with individual, recombinant CYP isoforms and their effect on the conversion of surrogate substances was measured fluorometrically in 96-well plates; enzyme inhibition was expressed as IC50 and Ki value in relation to positive controls. Crude essential oil demonstrated inhibition of each of the enzymes, with CYP1A2 being more sensitive than the other isoforms. Three constituents of the oil, namely chamazulene (IC50 = 4.41 microM), cis-spiroether (IC50 = 2.01 microM) and trans-spiroether (IC50 = 0.47 microM) showed to be potent inhibitors of this enzyme, also being active towards CYP3A4. CYP2C9 and CYP2D6 were less inhibited, only chamazulene (IC50 = 1.06 microM) and alpha-bisabolol (IC50 = 2.18 microM) revealed a significant inhibition of the latter. As indicated by these in vitro data, chamomile preparations contain constituents inhibiting the activities of major human drug metabolizing enzymes; interactions with drugs whose route of elimination is mainly via cytochromes (especially CYP1A2) are therefore possible.
Ganzera
M
M
Institute of Pharmacy, Department of Pharmacognosy, University of Innsbruck, Innrain 52, 6020 Innsbruck, Austria. Markus.Ganzera@uibk.ac.at
Schneider
P
P
Stuppner
H
H
D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors; D020843:Chamomile / Q000737:chemistry*; D002849:Chromatography, Gas; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors; D065729:Cytochrome P-450 CYP2C9; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D009822:Oils, Volatile / Q000494:pharmacology*; D010938:Plant Oils / Q000494:pharmacology*
D065690:Cytochrome P-450 CYP2D6 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D009822:Oils, Volatile; D010938:Plant Oils; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C104464:CYP3A protein, human; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human