CYP1A2 is the major isoform responsible for paeonol O-demethylation in human liver microsomes.
1. Paeonol, the primary active component of a traditional Chinese medicine Moutan Cortex, has a wide range of pharmacological activities. In the present study, the metabolism of paeonol by cytochrome P450s (CYPs) was investigated in human liver microsomes. 2. One O-demethylated metabolite was detected in reaction catalysed by human liver microsomes, and was identified as resacetophenone by comparing the tandem mass spectra and the chromatographic retention time with that of the standard compound. 3. The study with a chemical selective inhibitor, cDNA-expressed human CYPs, a correlation assay, and a kinetics study demonstrated that CYP1A2 was the major isoform responsible for the paeonol O-demethylation in human liver microsomes.
Liu
H-X
HX
Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
Hu
Y
Y
Liu
Y
Y
He
Y-Q
YQ
Li
W
W
Yang
L
L
D000098:Acetophenones / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D019388:Cytochrome P-450 CYP1A2 / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D020033:Protein Isoforms / Q000378:metabolism; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism*; D012118:Resorcinols / Q000737:chemistry / Q000378:metabolism*
D000098:Acetophenones; D004791:Enzyme Inhibitors; D020033:Protein Isoforms; D011994:Recombinant Proteins; D012118:Resorcinols; C013638:paeonol; D019388:Cytochrome P-450 CYP1A2; C412963:resacetophenone