Inhibitory effects of astaxanthin, β-cryptoxanthin, canthaxanthin, lutein, and zeaxanthin on cytochrome P450 enzyme activities

- AS, βC, CA, LU, and ZE, the major xanthophylls, are widely used in health care products.
- To date, no studies about their inhibitions on CYPs activities have been reported.
- It is the first time to evaluate their reversible inhibitory and TDI potentials on CYPs.
- These five xanthophylls had had only weak inhibitory effects on the nine CYPs.
- It is unlikely that these xanthophylls alter the pharmacokinetics of drugs metabolized by CYPs.

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.