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 K_i value of 5.08 μM, whereas CYP2C9 and 2D6 were fitted to a competitive model with K_i values of 6.25 and 8.14 μM. Additionally, the inhibitory effect on CYP3A4 was time-dependent with K_I value of 8.47 μM^-1 and a K_inact 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.