title: Selective inhibitory effects of mollugin on CYP1A2 in human liver microsomes.
abstract: Mollugin originally isolated from Rubia cordifolia is a pharmacological compound for its anti-inflammation, anti-cancer, and anti-viral activity. In the present study, a cocktail probe assay was performed for determination of the selective inhibitory effect of mollugin on cytochrome P450 (CYP) enzymes in human liver microsomes (HLM). Incubation of isoform-specific substrate probes CYPs with mollugin (0-25μM) in HLM resulted in strong inhibition of CYP1A2-catalyzed phenacetin O-deethylation, showing IC(50) values of 1.03 and 3.55μM without and with pre-incubation, respectively. Mollugin-caused inhibition of phenacetin O-deethylation was concentration-dependent in HLMs, but not time-dependent. In addition, the Lineweaver-Burk plot indicated a typical competitive inhibition. Inhibitory effects of mollugin on human recombinant cDNA-expressed CYP1A1 and 1A2 were comparable. Taken together, the results suggested that mollugin might cause herb-drug interaction through selective inhibition of CYP1A2 in humans receiving herbal medications, including R. cordifolia.
authors.affiliation: College of Pharmacy, Kyungpook National University, Daegu 702-701, South Korea.
authors.forename: Heeyeon
authors.initials: H
authors.lastname: Kim
authors.forename: Hyun Kyu
authors.initials: HK
authors.lastname: Choi
authors.forename: Tae Cheon
authors.initials: TC
authors.lastname: Jeong
authors.forename: Yurngdong
authors.initials: Y
authors.lastname: Jahng
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Seung-Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Sangkyu
authors.initials: S
authors.lastname: Lee
mesh_terms: D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D041743:Herb-Drug Interactions; D006801:Humans; D020128:Inhibitory Concentration 50; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology*; D011714:Pyrans / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D065609:Cytochrome P-450 CYP1A2 Inhibitors; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D011714:Pyrans; D011994:Recombinant Proteins; C046245:rubimaillin; C569463:CYP1A1 protein, human; C504573:CYP1A2 protein, human; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2