Effects of eupatilin and jaceosidin on cytochrome p450 enzyme activities in human liver microsomes

Eupatilin and jaceosidin are bioactive flavones found in the medicinal herbs of the genus Artemisia. These bioactive flavones exhibit various antioxidant, antiinflammatory, antiallergic, and antitumor activities. The inhibitory potentials of eupatilin and jaceosidin on the activities of seven major...

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Published in:Molecules (Basel, Switzerland) Switzerland), 2010-09, Vol.15 (9), p.6466-6475
Main Authors: Ji, Hye Young, Kim, Sung Yeon, Kim, Dong Kyun, Jeong, Ji Hyun, Lee, Hye Suk
Format: Article
Language:English
Subjects:
Antioxidants
Aryl Hydrocarbon Hydroxylases - antagonists & inhibitors
Competition
Cytochrome
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 CYP2C9
Cytochrome P-450 Enzyme Inhibitors
cytochrome P450 inhibition
Drug interactions
drug-drug interaction
Drugs, Chinese Herbal
Enzymes
eupatilin
Flavonoids - pharmacology
human liver microsomes
Humans
jaceosidin
Laboratory animals
Liver
Metabolism
Microsomes, Liver - enzymology
Nonsteroidal anti-inflammatory drugs
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Summary:Eupatilin and jaceosidin are bioactive flavones found in the medicinal herbs of the genus Artemisia. These bioactive flavones exhibit various antioxidant, antiinflammatory, antiallergic, and antitumor activities. The inhibitory potentials of eupatilin and jaceosidin on the activities of seven major human cytochrome P450 enzymes in human liver microsomes were investigated using a cocktail probe assay. Eupatilin and jaceosidin potently inhibited CYP1A2-catalyzed phenacetin O-deethylation with 50% inhibitory concentration (IC(50)) values of 9.4 microM and 5.3 microM, respectively, and CYP2C9-catalyzed diclofenac 4-hydroxylation with IC(50) values of 4.1 microM and 10.2 microM, respectively. Eupatilin and jaceosidin were also found to moderately inhibit CYP2C19-catalyzed [S]-mephenytoin 4'-hydroxylation, CYP2D6-catalyzed bufuralol 1'-hydroxylation, and CYP2C8-catalyzed amodiaquine N-deethylation. Kinetic analysis of human liver microsomes showed that eupatilin is a competitive inhibitor of CYP1A2 with a K(i) value of 2.3 microM and a mixed-type inhibitor of CYP2C9 with a K(i) value of 1.6 microM. Jaceosidin was shown to be a competitive inhibitor of CYP1A2 with a K(i) value of 3.8 microM and a mixed-type inhibitor of CYP2C9 with K(i) value of 6.4 microM in human liver microsomes. These in vitro results suggest that eupatilin and jaceosidin should be further examined for potential pharmacokinetic drug interactions in vivo due to inhibition of CYP1A2 and CYP2C9.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules15096466