Inhibition of cytochrome P450 3A4 by extracts and kavalactones of Piper methysticum (Kava-Kava).
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.
Unger
Matthias
M
Institute of Pharmacy and Food Chemistry, Julius-Maximilians-University, Würzburg, Germany. m.unger@pharmazie.uni-wuerzburg.de
Holzgrabe
Ulrike
U
Jacobsen
Wolfgang
W
Cummins
Carolyn
C
Benet
Leslie Z
LZ
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
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