Inhibitory Effect of Eurycoma Longifolia Extract and Eurycomanone on Human Cytochrome P450 Isoforms

Objective: The aim of this study was to evaluate the inhibitory effect of E. longifolia extract on five human cytochrome P450 isoforms. Methods: The inhibitory effect of E. longifolia standardized extract (TAF-273) on five human cytochrome P450 isoforms, namely CYP1A2, CYP3A4, CYP2C9, CYP2C19 and CYP2D6, was determined using a luminescence method. The effect of eurycomanone on cytochrome P450 isoforms CYP2C9 and CYP2C19 was examined using the same method. The final concentrations of E. longifolia extract tested were 0.01, 0.1, 1, 10, 100 and 1000 μg/mL, and eurycomanone was tested at concentrations ranging from 0.002 to 500 μM. Results: The extract decreased CYP2C9 and 2C19 activities, with IC50 values of 710.20 μg/mL and 739.05 μg/mL, respectively. The IC50 of TAF273’s inhibitory action on CYP2D6, CYP3A4 and CYP1A2 could not be determined because at the highest concentration tested (1000 μg/mL) the activity of each enzyme was still greater than 50 %. Eurycomanone (a marker compound in TAF-273) showed IC50 Conclusion: This inhibitory study showed that a standardized extract of E. longifolia was not a potent inhibitor towards CYP2C9, CYP2C19, CYP2D6, CYP3A4 and CYP1A2. On the other hand, eurycomanone (the marker compound) was a moderate inhibitor for CYP2C9 with an IC values of 47.33 μg/mL and 167.88 μg/mL in inhibiting the activities of CYP2C9 and 2C19.