Effects of the standardized extract of Centella asiatica ECa233 on human cytochrome P450

Abstract

The standardized extract of Centella asiatica ECa233 (ECa233) was shown to exhibit learning and memory enhancing effects. Beside toxicity testing data, safety data regarding drug interaction is also required. The purpose of this study was to investigate effects of ECa233 on major human cytochrome P450 (CYP) using in vitro recombinant human CYPs. The method was verified using the selective inhibitor of the individual CYP isoform. The results showed that ECa233 inhibited CYP3A4 (IC 50 = 210.98 ± 24.24 μg/ml), CYP2C19 (IC 50 = 365.18 ± 29.56 μg/ml) and CYP2B6 (IC 50 = 871.14 ± 41.30 μg/ml). ECa233 did not affect CYP1A2, CYP2C9, CYP2D6 and CYP2E1. Inhibition of ECa233 on CYP3A4 was shown to be mechanism-based as well as non-competitive inhibition with a K i value of 281.32 ± 4.39 μg/ml. This finding provides a preliminary information that ECa233 possesses a potential effect to interact with other medicines that are metabolized by CYP3A4, CYP2C19 and CYP2B6. Further study is needed to investigate whether or not this effect is clinically significant.