TY - JOUR
T1 - In vitro inhibition of human cytochrome P450 by cudratricusxanthone A
AU - Sim, Juhee
AU - Choi, Eunhwa
AU - Lee, You Mie
AU - Jeong, Gil Saeng
AU - Lee, Sangkyu
N1 - Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - Cudratricusxanthone A (CTXA) isolated from the roots of Cudrania tricuspidata Bureau (Moraceae) has several biological activities, including hepatoprotective, neuroprotective, anti-inflammatory, monoamine oxidase inhibitory, and antithrombotic activities. In this study, we investigated the potential herb-drug interaction of CTXA and nine cytochrome P450 (CYP) isoforms in pooled human liver microsomes (HLMs) using a cocktail probe assay. CTXA reversibly inhibited the CYP1A2-catalyzed phenacetin O-deethylation, CYP2C8-catalyzed paclitaxel 6-hydroxylation, and CYP2C9-catalyzed diclofenac 4'-hydroxylation with half-maximal inhibitory concentration (IC50) values of 3.9, 4.7, and 2.9 μM, respectively. The IC50 values did not change under different preincubation conditions. CTXA showed marked dose-dependent, but not time-dependent, inhibition of CYP1A2 and 2C9 activities in HLMs. Dixon plots showed typical competitive inhibition of CYP1A2 and CYP2C9 with Ki values of 1.3 and 1.5 μM, respectively. Further, CTXA inhibited CYP2C8 in a non-competitive manner with a Ki value of 2.2 μM. Our results showed that CTXA reversibly inhibits CYP1A2, 2C8, and 2C9.
AB - Cudratricusxanthone A (CTXA) isolated from the roots of Cudrania tricuspidata Bureau (Moraceae) has several biological activities, including hepatoprotective, neuroprotective, anti-inflammatory, monoamine oxidase inhibitory, and antithrombotic activities. In this study, we investigated the potential herb-drug interaction of CTXA and nine cytochrome P450 (CYP) isoforms in pooled human liver microsomes (HLMs) using a cocktail probe assay. CTXA reversibly inhibited the CYP1A2-catalyzed phenacetin O-deethylation, CYP2C8-catalyzed paclitaxel 6-hydroxylation, and CYP2C9-catalyzed diclofenac 4'-hydroxylation with half-maximal inhibitory concentration (IC50) values of 3.9, 4.7, and 2.9 μM, respectively. The IC50 values did not change under different preincubation conditions. CTXA showed marked dose-dependent, but not time-dependent, inhibition of CYP1A2 and 2C9 activities in HLMs. Dixon plots showed typical competitive inhibition of CYP1A2 and CYP2C9 with Ki values of 1.3 and 1.5 μM, respectively. Further, CTXA inhibited CYP2C8 in a non-competitive manner with a Ki value of 2.2 μM. Our results showed that CTXA reversibly inhibits CYP1A2, 2C8, and 2C9.
KW - Cudratricusxanthone A
KW - Cytochrome P450
KW - Human liver microsomes
KW - Inhibition
KW - Interaction
UR - http://www.scopus.com/inward/record.url?scp=84929146622&partnerID=8YFLogxK
U2 - 10.1016/j.fct.2015.04.024
DO - 10.1016/j.fct.2015.04.024
M3 - Article
C2 - 25936586
AN - SCOPUS:84929146622
SN - 0278-6915
VL - 81
SP - 171
EP - 175
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
ER -