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. 2010 Sep 16;15(9):6466-75.
doi: 10.3390/molecules15096466.

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

Hye Young Ji  1 , Sung Yeon Kim, Dong Kyun Kim, Ji Hyun Jeong, Hye Suk Lee
Affiliations

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

Hye Young Ji et al. Molecules. .

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 (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.

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Figures

Figure 1
Figure 1
Representative Dixon plots for inhibitory effects of eupatilin on (a) CYP1A2-catalyzed phenacetin O-deethylation, (b) CYP2C8-catalyzed amodiaquine N-deethylation, (c) CYP2C9-catalyzed diclofenac 4-hydroxylation, (d) CYP2C19-catalyzed [S]-mephenytoin 4'-hydroxylation, and (e) CYP2D6-catalyzed bufuralol 1'-hydroxylation in pooled human liver microsomes. Each symbol represents the substrate concentration. (a) phenacetin: 10 μM (▽), 20 μM (○), 40 μM (△), and 80 μM (□); (b) amodiaquine:0.5 μM (▽), 1.0 μM (○), 2.0 μM (△), and 5.0 μM (□); (c) diclofenac: 1 μM (▽), 5 μM (○),10 μM (△), and 50 μM (□); (d) [S]-mephenytoin: 10 μM (▽), 20 μM (○), 50 μM (△), and 100 μM (□); (e) bufuralol: 0.5 μM (▽), 1.0 μM (○), 2.0 μM (△), and 5.0 μM (□). Each data point represents the mean of triplicate experiments.
Figure 2
Figure 2
Representative Dixon plots for inhibitory effects of jaceosidin on (a) CYP1A2-catalyzed phenacetin O-deethylation, (b) CYP2C8-catalyzed amodiaquine N-deethylation, (c) CYP2C9-catalyzed diclofenac 4-hydroxylation, (d) CYP2C19-catalyzed [S]-mephenytoin 4'-hydroxylation, and (e) CYP2D6-catalyzed bufuralol 1'-hydroxylation in pooled human liver microsomes. Each symbol represents the substrate concentration. (a) phenacetin: 10 μM (▽), 20 μM (○), 40 μM (△), and 80 μM (□); (b) amodiaquine:0.5 μM (▽), 1.0 μM (○), 2.0 μM (△), and 5.0 μM (□); (c) diclofenac: 1 μM (▽), 5 μM (○),10 μM (△), and 50 μM (□); (d) [S]-mephenytoin: 10 μM (▽), 20 μM (○), 50 μM (△), and 100 μM (□); (e) bufuralol: 0.5 μM (▽), 1.0 μM (○), 2.0 μM (△), and 5.0 μM (□). Each data point represents the mean of triplicate experiments.
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References

    1. Kim A.R., Zou Y.N., Park T.H., Shim K.H., Kim M.S., Kim N.D., Kim J.D., Bae S.J., Choi J.S., Chung H.Y. Active components from Artemisia iwayomogi displaying ONOO(-) scavenging activity. Phytother. Res. 2004;18:1–7. - PubMed
    1. Moscatelli V., Hnatyszyn O., Acevedo C., Megias J., Alcaraz M.J., Ferraro G. Flavonoids from Artemisia copa with anti-inflammatory activity. Planta Med. 2006;72:72–74. - PubMed
    1. Clavin M., Gorzalczany S., Macho A., Munoz E., Ferraro G., Acevedo C., Martino V. Anti-inflammatory activity of flavonoids from Eupatorium arnottianum. J. Ethnopharmacol. 2007;112:585–589. doi: 10.1016/j.jep.2007.04.007. - DOI - PubMed
    1. Choi E.J., Oh H.M., Na B.R., Ramesh T.P., Lee H.J., Choi C.S., Choi S.C., Kim K.H., Oh T.Y., Choi S.J., Chae J.R., Kim S.W., Jun C.D. Eupatilin protects gastric epithelial cells from oxidative damage and down-regulates genes responsible for the cellular oxidative stress. Pharm. Res. 2008;25:1355–1364. doi: 10.1007/s11095-008-9531-5. - DOI - PubMed
    1. Kim M.J., Han J.M., Jin Y.Y., Baek N.I., Bang M.H., Chung H.G., Choi M.S., Lee K.T., Sok D.E., Jeong T.S. In vitro antioxidant and anti-inflammatory activities of jaceosidin from Artemisia princeps Pampanini cv. Sajabal. Arch. Pharm. Res. 2008;31:429–437. doi: 10.1007/s12272-001-1175-8. - DOI - PubMed

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