Molecules 2010, 15(9), 6466-6475; doi:10.3390/molecules15096466
Article

Effects of Eupatilin and Jaceosidin on Cytochrome P450 Enzyme Activities in Human Liver Microsomes

Drug Metabolism & Bioanalysis Laboratory, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea # These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 7 September 2010; in revised form: 10 September 2010 / Accepted: 14 September 2010 / Published: 16 September 2010
(This article belongs to the collection Bioactive Compounds)
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Abstract: 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 (IC50) values of 9.4 mM and 5.3 mM, respectively, and CYP2C9-catalyzed diclofenac 4-hydroxylation with IC50 values of 4.1 mM and 10.2 mM, 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 Ki value of 2.3 mM and a mixed-type inhibitor of CYP2C9 with a Ki value of 1.6 mM. Jaceosidin was shown to be a competitive inhibitor of CYP1A2 with a Ki value of 3.8 mM and a mixed-type inhibitor of CYP2C9 with Ki value of 6.4 mM 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.
Keywords: eupatilin; jaceosidin; cytochrome P450 inhibition; human liver microsomes; drug-drug interaction

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MDPI and ACS Style

Ji, H.Y.; Kim, S.Y.; Kim, D.K.; Jeong, J.H.; Lee, H.S. Effects of Eupatilin and Jaceosidin on Cytochrome P450 Enzyme Activities in Human Liver Microsomes. Molecules 2010, 15, 6466-6475.

AMA Style

Ji HY, Kim SY, Kim DK, Jeong JH, Lee HS. Effects of Eupatilin and Jaceosidin on Cytochrome P450 Enzyme Activities in Human Liver Microsomes. Molecules. 2010; 15(9):6466-6475.

Chicago/Turabian Style

Ji, Hye Young; Kim, Sung Yeon; Kim, Dong Kyun; Jeong, Ji Hyun; Lee, Hye Suk. 2010. "Effects of Eupatilin and Jaceosidin on Cytochrome P450 Enzyme Activities in Human Liver Microsomes." Molecules 15, no. 9: 6466-6475.

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