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Effects of 6-paradol, an unsaturated ketone from gingers, on cytochrome P450-mediated drug metabolism
- Authors
- Kim, Hyeong Jun; Kim, In Sook; Rehman, Shaheed Ur; Ha, Sang Keun; Nakamura, Katsunori; Yoo, Hye Hyun
- Issue Date
- Apr-2017
- Publisher
- Pergamon Press Ltd.
- Keywords
- 6-Paradol; Unsaturated ketone; Ginger; CYP inhibition; Drug-drug interaction
- Citation
- Bioorganic and Medicinal Chemistry Letters, v.27, no.8, pp.1826 - 1830
- Indexed
- SCIE
SCOPUS
- Journal Title
- Bioorganic and Medicinal Chemistry Letters
- Volume
- 27
- Number
- 8
- Start Page
- 1826
- End Page
- 1830
- ISSN
- 0960-894X
- Abstract
- Paradols are unsaturated ketones produced by biotransformation of shogaols in gingers. Among them, 6-paradol has been investigated as a new drug candidate due to its anti-inflammatory, apoptotic, and neuroprotective activities. In this study, the inhibitory effects of 6-paradol on the activities of cytochrome P450 (CYP) enzymes were investigated with human liver microsomes and recombinant CYP isozymes. 6-Paradol showed concentration-dependent inhibitory effects on CYP1A2, CYP2B6, CYP2C8, CYP2C9, and CYP2C19 isozymes, with IC50, values ranging from 3.8 to 21.4 mu M in recombinant CYP isozymes. However, the inhibition was not potentiated following pre-incubation, indicating that 6-paradol is not a mechanism-based inhibitor. These results suggest that pharmacokinetic drug-drug interactions might occur with 6-paradol, which must be considered in the process of new drug development. (C) 2017 Elsevier Ltd. All rights reserved.
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Related Researcher
- Yoo, Hye Hyun
- COLLEGE OF PHARMACY (DEPARTMENT OF PHARMACY)