Abstract |
Mollugin originally isolated from Rubia cordifolia is a pharmacological compound for its anti- inflammation, anti- cancer, and anti-viral activity. In the present study, a cocktail probe assay was performed for determination of the selective inhibitory effect of mollugin on cytochrome P450 (CYP) enzymes in human liver microsomes (HLM). Incubation of isoform-specific substrate probes CYPs with mollugin (0-25μM) in HLM resulted in strong inhibition of CYP1A2-catalyzed phenacetin O-deethylation, showing IC(50) values of 1.03 and 3.55μM without and with pre-incubation, respectively. Mollugin-caused inhibition of phenacetin O-deethylation was concentration-dependent in HLMs, but not time-dependent. In addition, the Lineweaver-Burk plot indicated a typical competitive inhibition. Inhibitory effects of mollugin on human recombinant cDNA-expressed CYP1A1 and 1A2 were comparable. Taken together, the results suggested that mollugin might cause herb-drug interaction through selective inhibition of CYP1A2 in humans receiving herbal medications, including R. cordifolia.
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Authors | Heeyeon Kim, Hyun Kyu Choi, Tae Cheon Jeong, Yurngdong Jahng, Dong Hyun Kim, Seung-Ho Lee, Sangkyu Lee |
Journal | Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
(Food Chem Toxicol)
Vol. 51
Pg. 33-7
(Jan 2013)
ISSN: 1873-6351 [Electronic] England |
PMID | 23000442
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Ltd. All rights reserved. |
Chemical References |
- Cytochrome P-450 CYP1A2 Inhibitors
- Drugs, Chinese Herbal
- Enzyme Inhibitors
- Pyrans
- Recombinant Proteins
- rubimaillin
- CYP1A1 protein, human
- CYP1A2 protein, human
- Cytochrome P-450 CYP1A1
- Cytochrome P-450 CYP1A2
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Topics |
- Cytochrome P-450 CYP1A1
(genetics, metabolism)
- Cytochrome P-450 CYP1A2
(genetics, metabolism)
- Cytochrome P-450 CYP1A2 Inhibitors
- Drugs, Chinese Herbal
(pharmacology)
- Enzyme Inhibitors
(pharmacology)
- Herb-Drug Interactions
- Humans
- Inhibitory Concentration 50
- Microsomes, Liver
(drug effects, enzymology)
- Pyrans
(pharmacology)
- Recombinant Proteins
(genetics, metabolism)
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