title: Inhibitory effects of astaxanthin, β-cryptoxanthin, canthaxanthin, lutein, and zeaxanthin on cytochrome P450 enzyme activities.
abstract: Astaxanthin, β-cryptoxanthin, canthaxanthin, lutein and zeaxanthin, the major xanthophylls, are widely used in food, medicine, and health care products. To date, no studies regarding the inhibitory effects of these xanthophylls on the nine CYPs isozymes have been reported. This study investigated the reversible and time-dependent inhibitory potentials of five xanthophylls on CYPs activities in vitro. The reversible inhibition results showed that the five compounds had only a weak inhibitory effect on the nine CYPs. Lutein did not inhibit the nine CYPs activities. Astaxanthin weakly inhibited CYP2C19, with an IC₅₀ of 16.2 μM; and β-cryptoxanthin weakly inhibited CYP2C8, with an IC₅₀ of 13.8 μM. In addition, canthaxanthin weakly inhibited CYP2C19 and CYP3A4/5, with IC₅₀ values of 10.9 and 13.9 μM, respectively. Zeaxanthin weakly inhibited CYP3A4/5, with an IC₅₀ of 15.5 μM. However, these IC₅₀ values were markedly greater than the Cmax values reported in humans. No significant IC₅₀ shift was observed in the time-dependent inhibition screening. Based on these observations, it is unlikely that these five xanthophylls from the diet or nutritional supplements alter the pharmacokinetics of drugs metabolized by CYPs. These findings provide some useful information for the safe use of these five xanthophylls in clinical practice.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Yu Fen
authors.initials: YF
authors.lastname: Zheng
authors.forename: Soo Hyeon
authors.initials: SH
authors.lastname: Bae
authors.forename: Min Jo
authors.initials: MJ
authors.lastname: Kwon
authors.forename: Jung Bae
authors.initials: JB
authors.lastname: Park
authors.forename: Hye Duck
authors.initials: HD
authors.lastname: Choi
authors.forename: Wan Gyoon
authors.initials: WG
authors.lastname: Shin
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Bae
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D001711:Biotransformation; D016644:Canthaxanthin / Q000009:adverse effects / Q000378:metabolism; D002338:Carotenoids / Q000009:adverse effects / Q000378:metabolism*; D065366:Cryptoxanthins; D065731:Cytochrome P-450 CYP2C19; D065727:Cytochrome P-450 CYP2C8; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D019587:Dietary Supplements / Q000009:adverse effects; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000378:metabolism*; D018565:Food-Drug Interactions; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007700:Kinetics; D014975:Lutein / Q000009:adverse effects / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D024341:Xanthophylls / Q000009:adverse effects / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism*; D065146:Zeaxanthins
chemical_list: D065366:Cryptoxanthins; D065692:Cytochrome P-450 CYP3A Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D024341:Xanthophylls; D015262:Xenobiotics; D065146:Zeaxanthins; D002338:Carotenoids; D016644:Canthaxanthin; C005948:astaxanthine; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; C450259:CYP2C8 protein, human; C510164:CYP3A5 protein, human; D065731:Cytochrome P-450 CYP2C19; D065727:Cytochrome P-450 CYP2C8; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D014975:Lutein
keywords: AS; Astaxanthin; C(max); CA; CYP; Canthaxanthin; IC(50); In vitro CYPs inhibition; LC–MS/MS; LU; Lutein; NADP(+); ZE; Zeaxanthin; astaxanthin; canthaxanthin; cytochrome P450; liquid chromatography–tandem mass spectrometry; lutein; maximum plasma concentration; the 50% inhibitory concentration; zeaxanthin; β-Cryptoxanthin; β-cryptoxanthin; β-nicotinamide adenine dinucleotide phosphate; βC