In vitro evaluation of the inhibition potential of echinacoside on human cytochrome P450 isozymes

Echinacoside (ECH) possesses a wide range of biological activity. This present study analyzes the effect of ECH on cytochrome P450 isozymes (CYPs) activities of human liver microsomes.

The effect of ECH on CYPs enzyme activities were studied using the enzyme-selective substrates phenacetin (1A2), chlorzoxazone (2E1), S-mephenytoin (2C19), testosterone (3A4), coumarin (2A6), diclofenac (2C9), paclitaxel (2C8), and dextromethorphan (2D6). The IC50 values for CYP1A2, CYP2E1, CYP2C19, and CYP3A4 isoforms were examined to express the strength of inhibition. Further, the inhibition of CYPs was checked for time-dependent or not, and then fitted with competitive or non-competitive inhibition models. The corresponding parameters were also obtained.

ECH caused inhibitions on CYP1A2, CYP2E1, CYP2C19 and CYP3A4 enzyme activities in HLMs with IC50 of 21.23, 19.15, 8.70 and 55.42 μM, respectively. The obtained results showed that the inhibition of ECH on CYP3A4 was time-dependent with the KI/K_inact value of 6.63/0.066 min^- 1·μM^- 1. Moreover, ECH inhibited the activity of CYP1A2 and CYP2E1 via non-competitive manners (K_i = 10.90 μM and K_i = 14.40 μM, respectively), while ECH attenuated the CYP2C19 activity via a competitive manner (K_i = 4.41 μM).

The results of this study indicate that ECH inhibits CYP1A2, CYP2E1, CYP2C19 and CYP3A4 activities in vitro. In vivo and clinical studies are warranted to verify the relevance of these interactions.