Rehmannioside A inhibits the activity of CYP3A4, 2C9 and 2D6 in vitro.

To assess the effect of Rehmannioside A on CYP450s activity and to estimate its inhibitory properties. The effect of Rehmannioside A on the activity of major CYP450s in human liver microsomes (HLMs) was assessed with the corresponding substrates and marker reactions, and compared with a blank control and the respective inhibitors. Suppression of CYP3A4, 2C9 and 2D6 was assessed by the dose-dependent assay and fitted with non-competitive or competitive inhibition models. The inhibition of CYP3A4 was determined in a time-dependent manner. Rehmannioside A suppressed the activity of CYP3A4, 2C9, and 2D6 with IC50 values of 10.08, 12.62, and 16.43 μM, respectively. Suppression of CYP3A4 was fitted to a non-competitive model with Ki value of 5.08 μM, whereas CYP2C9 and 2D6 were fitted to a competitive model with Ki values of 6.25 and 8.14 μM. Additionally, the inhibitory effect on CYP3A4 was time-dependent with KI value of 8.47 μM−1 and a Kinact of 0.048 min−1. In vitro suppression of CYP3A, 2C9 and 2D6 by Rehmannioside A indicated that Rehmannioside A or its source herbs may interact with drugs metabolised by these CYP450s, which could guide the clinical application. [ABSTRACT FROM AUTHOR]