Inhibition of Chinese herbal extracts on CYP1A and CYP3A of liver microsomes from crucian carp (Carassius auratus gibelio)

Abstract:

This study focused on the inhibition of five kinds of Chinese herbal extracts (Scutellaria, Forsythia, Bupleurum, Evodia and Chrysanthemum) on CYP1A and CYP3A of crucian carp (Carassius auratus gibelio) liver microsomes. IC50 and kinetic parameters of enzymatic reaction were determined in vitro and the inhibition mechanism was speculated. The results showed that the level of inhibition of five kinds of Chinese herb extracts on CYP1A was Scutellaria>Forsythia>Chrysanthemum>Bupleurum≈Evodia; the IC₅₀ were 0.27，2.88，7.62，16.20 and 16.42 mg/mL, and the inhibition instants (K_i) were 0.13, 0.38, 3.39, 1.74 and 70 mg/mL respectively. The kinetic parameters of enzymatic reaction, V_max and K_m were （83.33±11.32） pmol/(min·mg) and （3.05±0.89 ）μmol/L, respectively. Scutellaria, Forsythia and Bupleuru had a weak inhibition on CYP3A activity with the IC₅₀ of 90.9, 70.8 and 43.5 mg/mL, respectively. No inhibition was observed for Chrysanthemum and Bupleurum on CYP3A. Furthermore, it was speculated that Scutellaria, Chrysanthemum and Bupleurum were competitive inhibitors, while Evodia and Forsythia were uncompetitive inhibitors. In this study, inhibition of five Chinese herbs on the CYP450 enzymes varied greatly due to different subtypes and it showed that the inhibition on CYP1A was significant but no significant inhibition on CYP3A. It suggested that the inhibition of CYP450 isoenzyme by herb extracts might lead to increase plasma levels and change the pharmacokinetics of drug metabolized by these isoenzymes, therefore, more care is needed when using the coadministered prescription drugs.