Effect of Honokiol on Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes
Abstract
:1. Introduction
2. Results and Discussion
CYP activity | CYP | IC50 (μM) of honokiol | |
---|---|---|---|
no preincubation | with preincubation * | ||
Phenacetin O-deethylation | 1A2 | 2.1 | 4.7 |
Coumarin 7-hydroxylation | 2A6 | No inhibition | No inhibition |
Bupropion hydroxylation | 2B6 | 13.8 | 20.8 |
Amodiaquine N-deethylation | 2C8 | 8.9 | 15.5 |
Diclofenac 4-hydroxylation | 2C9 | 4.1 | 3.9 |
S-Mephenytoin 4'-hydroxylation | 2C19 | 2.2 | 2.9 |
Bufuralol 1'-hydroxylation | 2D6 | 14.0 | 38.1 |
Midazolam 1'-hydroxylation | 3A4 | 97.3 | 45.8 |
Enzymes | Marker reactions | Ki (μM) | Inhibition mode |
---|---|---|---|
CYP1A2 | Phenacetin O-deethylation | 1.2 | noncompetitive |
CYP2B6 | Bupropion hydroxylation | 17.5 | competitive |
CYP2C8 | Amodiaquine N-deethylation | 4.9 | competitive |
CYP2C9 | Diclofenac 4-hydroxylation | 0.54 | competitive |
CYP2C19 | S-Mephenytoin 4'-hydroxylation | 0.57 | competitive |
CYP2D6 | Bufuralol 1'-hydroxylation | 12.0 | competitive |
UGT1A9 | Propofol glucuronidation | 0.3 | competitive |
UGT | Marker enzyme | IC50 (μM) |
---|---|---|
UGT1A1 | 17β-estradiol 3-glucuronidation | 50.5 |
UGT1A4 | trifluoperazine N-glucuronidation | 158.1 |
UGT1A9 | propofol glucuronidation | 0.96 |
UGT2B7 | azidothymidine glucuronidation | 36.4 |
3. Experimental
3.1. Materials
3.2. Inhibitory Effect of Honokiol on Eight Major CYP Activities in Human Liver Microsomes
3.3. Inhibitory Effect of Honokiol on Four UGT Activities in Human Liver Microsomes
3.4. Kinetic Analysis
3.5. Data Analysis
4. Conclusions
Acknowledgments
Conflicts of Interest
References
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Jeong, H.-U.; Kong, T.Y.; Kwon, S.S.; Hong, S.-W.; Yeon, S.H.; Choi, J.-H.; Lee, J.Y.; Cho, Y.Y.; Lee, H.S. Effect of Honokiol on Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes. Molecules 2013, 18, 10681-10693. https://doi.org/10.3390/molecules180910681
Jeong H-U, Kong TY, Kwon SS, Hong S-W, Yeon SH, Choi J-H, Lee JY, Cho YY, Lee HS. Effect of Honokiol on Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes. Molecules. 2013; 18(9):10681-10693. https://doi.org/10.3390/molecules180910681
Chicago/Turabian StyleJeong, Hyeon-Uk, Tae Yeon Kong, Soon Sang Kwon, Sung-Woon Hong, Sung Hum Yeon, Jun-Ho Choi, Jae Young Lee, Yong Yeon Cho, and Hye Suk Lee. 2013. "Effect of Honokiol on Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes" Molecules 18, no. 9: 10681-10693. https://doi.org/10.3390/molecules180910681