Effect of Equisetum arvense L. Extract on Cytochrome P-450 Activities in Human Liver Microsomes and Prediction of Interaction with Blood Drug Metabolism

Abstract

We examined the metabolic interaction with drugs produced by intake of horsetail (Equisetum arvense L.). The inhibitory effects of Equisetum arvense L. extract (Equisetum extract) on the metabolic activities of drugs with specific activity on cytochrome P-450 isozymes (1A2, 2C9, 2C19, 2D6, 2E1, and 3A4) were investigated using human liver microsomes. Equisetum extract (final concentration: 0, 0.1, 1, 10, and 100 μg/mL) and the respective representative substrates for CYP1A2, 2C9, 2C19, 2D6, 2E1, and 3A4 were incubated with human liver microsomes in order to examine the inhibitory effect. In the presence of Equisetum extract at 0.1 to 10 μg/mL, the residual activity of all the CYP isozymes examined was 68.2 to 105.3% of control, indicating no inhibition. Although CYP2D6 and CYP2E retained 66.7% and 73.4% of activity at Equisetum extract concentration of 100 μg/mL, the highest concentration examined in the tests, the residual activities of CYP1A2, 2C9, 2C19, and 3A4 were 21.4, 10.6, 8.9, and 8.6% respectively, showing IC50 values of 31.1, 22.3, 18.8, and 23.5 μg/mL, respectively. Certain components of Equisetum extract, such as flavons, appear to have inhibitory effect; but the amount of Equisetum extract required to exert the inhibitory effect on CYP isozymes is the same. Assuming that all components of the added Equisetum extract have inhibitory activity and that the mean molecular weight of such inhibitory components is 500, the IC50 values were converted into Ki values using Cheng-Prusoff’s equation; giving Ki values of the order of 10 μM. According to Rowland’s equation for estimating the rate of increase in AUC caused by drug-drug interactions, this suggests that there is no increase in AUC caused by the inhibitory effect of Equisetum arvense extract on CYP isozymes. This is a convenient method of estimating the degree of metabolic interaction between food and drugs.