title: Inhibition of cytochrome P450 3A4 by extracts and kavalactones of Piper methysticum (Kava-Kava).
abstract: Inhibitors of cytochrome P450 3A4 (CYP3A4) were identified in crude extracts from the rhizomes of Piper methysticum G. Forst. (Kava-Kava) using bioassay-guided fractionation. After preliminary purification of an ethyl acetate extract with solid phase extraction, the eluate was further fractionated by means of HPLC and fractions were tested for inhibitory potency using cDNA expressed CYP3A4. Positive fractions were analysed with LC/MS using electrospray ionisation and kavapyrones could be identified as the main CYP3A4 inhibitory components of Piper methysticum.
authors.affiliation: Institute of Pharmacy and Food Chemistry, Julius-Maximilians-University, Würzburg, Germany. m.unger@pharmazie.uni-wuerzburg.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Unger
authors.forename: Ulrike
authors.initials: U
authors.lastname: Holzgrabe
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Jacobsen
authors.forename: Carolyn
authors.initials: C
authors.lastname: Cummins
authors.forename: Leslie Z
authors.initials: LZ
authors.lastname: Benet
mesh_terms: D000840:Anisoles / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D020901:Kava; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D013058:Mass Spectrometry; D015394:Molecular Structure; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D011714:Pyrans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D011753:Pyrones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D027343:Rhizome / Q000737:chemistry
chemical_list: C107882:7,8-dihydromethysticin; D000840:Anisoles; D065607:Cytochrome P-450 Enzyme Inhibitors; D007783:Lactones; D010936:Plant Extracts; D011714:Pyrans; D011753:Pyrones; C472145:dihydroyangonin; C113859:dihydrokavain; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C076881:methysticin; C011889:kavain