TY - JOUR
T1 - Selective inhibition of the cytochrome P450 isoform by hyperoside and its potent inhibition of CYP2D6
AU - Song, Min
AU - Hong, Miri
AU - Lee, Min Young
AU - Jee, Jun Goo
AU - Lee, You Mie
AU - Bae, Jong Sup
AU - Jeong, Tae Cheon
AU - Lee, Sangkyu
PY - 2013/9
Y1 - 2013/9
N2 - Hyperoside, quercetin-3-O-galactoside, is a flavonoid isolated from Oenanthe javanica. In the present study, we investigated potential herb-drug inhibitory effects of hyperoside on nine cytochrome P450 (CYP) isoforms in pooled human liver microsomes (HLMs) and human recombinant cDNA expressed CYP using a cocktail probe assay. Hyperoside strongly inhibited CYP2D6-catalyzed dextromethorphan O-demethylation, with IC50 values of 1.2 and 0.81μM after 0 and 15min of preincubation, and a Ki value of 2.01μM in HLMs, respectively. Hyperoside strongly decreased CYP2D6 activity dose-, but not time-, dependently in HLMs. In addition, the Lineweaver-Burk and Secondary plots for the inhibition of CYP2D6 in HLMs fitted a competitive inhibition mode. Furthermore, hyperoside decreased CYP2D6-catalyzed dextromethorphan O-demethylation activity of human recombinant cDNA-expressed CYP2D6, with an IC50 value of 3.87μM. However, other CYPs were not inhibited significantly by hyperoside. In conclusion, our data demonstrate that hyperoside is a potent selective CYP2D6 inhibitor in HLMs, and suggest that hyperoside might cause herb-drug interactions when co-administrated with CYP2D substrates.
AB - Hyperoside, quercetin-3-O-galactoside, is a flavonoid isolated from Oenanthe javanica. In the present study, we investigated potential herb-drug inhibitory effects of hyperoside on nine cytochrome P450 (CYP) isoforms in pooled human liver microsomes (HLMs) and human recombinant cDNA expressed CYP using a cocktail probe assay. Hyperoside strongly inhibited CYP2D6-catalyzed dextromethorphan O-demethylation, with IC50 values of 1.2 and 0.81μM after 0 and 15min of preincubation, and a Ki value of 2.01μM in HLMs, respectively. Hyperoside strongly decreased CYP2D6 activity dose-, but not time-, dependently in HLMs. In addition, the Lineweaver-Burk and Secondary plots for the inhibition of CYP2D6 in HLMs fitted a competitive inhibition mode. Furthermore, hyperoside decreased CYP2D6-catalyzed dextromethorphan O-demethylation activity of human recombinant cDNA-expressed CYP2D6, with an IC50 value of 3.87μM. However, other CYPs were not inhibited significantly by hyperoside. In conclusion, our data demonstrate that hyperoside is a potent selective CYP2D6 inhibitor in HLMs, and suggest that hyperoside might cause herb-drug interactions when co-administrated with CYP2D substrates.
KW - CYP2D6
KW - Herb-drug interaction
KW - Human liver microsomes
KW - Hyperoside
KW - Inhibitor
UR - https://www.scopus.com/pages/publications/84880971924
U2 - 10.1016/j.fct.2013.06.055
DO - 10.1016/j.fct.2013.06.055
M3 - Article
C2 - 23835282
AN - SCOPUS:84880971924
SN - 0278-6915
VL - 59
SP - 549
EP - 553
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
ER -