The effect of standardized Echinacea purpurea extract on rat cytochrome P450 expression level

Abstract

It is claimed that application of botanical supplements or herbal medicinal products with synthetic drugs that are cytochrome P450 enzymes substrates may induce significant herb-drug interactions and may alter pharmacotherapy. Echinacea preparations are one of the best selling products in the Europe and their medicinal use is still increasing but data about interactions of Echinacea extract with CYP enzymes are limited. In this study, we have investigated potential influence of standardized Echinacea purpurea extract containing 3.7% polyphenolic compounds on the mRNA expression level of major CYP450 enzymes using animal model. Total RNA was isolated from the rat liver tissue according to the manufacturer's protocol. Complementary DNA was synthesized from a mature mRNA template using reverse transcription. The level of mRNA expression in liver was analyzed by real-time quantitative PCR using specific target primers for CYP450 genes. In this study, it was demonstrated a significant increase of rat CYP2D1 and CYP1A1 expression level by 40% (p = 0.007) and 80% (p = 0.01), respectively. A weak inductory effect of the extract was observed for CYP1A2 by 16% (p > 0.05) compared with the control group. The levels of rat CYP3A1 and CYP3A2 mRNA were reduced by 41% (p < 0.05) and 25% (p = 0.001), respectively. A weak inhibitory effect was observed for CYP2D2 by 15% (p = 0.008) and CYP2C6 by 18% (p = 0.004) after long application of the Echinacea ethanolic extract. CYP2D2 and CYP2C6 activities were also inhibited by extract but in a lesser degree than CYP3A1 activity. Moreover, very little or no inhibition was noted for CYP2E1 both after 3 and 10 days of treatment. Our in vivo data indicate that the Echinacea ethanolic extract can potently inhibit the expression of CYP3A1/2 and can also induce of CYP1A1, CYP2D1. These findings suggest that Echinacea extract may influence the P450-mediated metabolism of different drugs and may initiate chemical carcinogenesis by activation of some compounds to their carcinogenic metabolites.