title: Effects of 6-paradol, an unsaturated ketone from gingers, on cytochrome P450-mediated drug metabolism.
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 IC50values ranging from 3.8 to 21.4µM 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.
authors.affiliation: Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan-si, Gyeonggi-do 15588, Republic of Korea.
authors.forename: Hyeong Jun
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan-si, Gyeonggi-do 15588, Republic of Korea.
authors.forename: In Sook
authors.initials: IS
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan.
authors.forename: Shaheed Ur
authors.initials: SU
authors.lastname: Rehman
authors.affiliation: Korea Food Research Institute, Seongnam, Gyeonggi-do 426-791, Republic of Korea.
authors.forename: Sang Keun
authors.initials: SK
authors.lastname: Ha
authors.affiliation: Department of Pharmacy, Ryukyu University Hospital, 207 Uehara, Nishihara-cho, Okinawa 903-0215, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan-si, Gyeonggi-do 15588, Republic of Korea. Electronic address: yoohh@hanyang.ac.kr.
authors.forename: Hye Hyun
authors.initials: HH
authors.lastname: Yoo
mesh_terms: D065607:Cytochrome P-450 Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D020939:Zingiber officinale / Q000737:chemistry*; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007659:Ketones / Q000737:chemistry / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D007659:Ketones; D004364:Pharmaceutical Preparations; D011994:Recombinant Proteins; D006139:Guaiacol; D003577:Cytochrome P-450 Enzyme System; C421614:6-paradol
keywords: 6-Paradol; CYP inhibition; Drug-drug interaction; Ginger; Unsaturated ketone