Assessment of drug interaction potential of Eschscholzia californica (California poppy) through modulation of CYPs, P-gp and PXR

Abstract

Eschscholzia californica, a North American plant, is traditionally used for depression, neurasthenia, and various psychiatric conditions. With the rapid rise in the use of herbal supplements in combination with conventional drugs, the risk for potential herb-drug interactions is also increasing. Most of the clinically relevant pharmacokinetic drug interactions occur due to modulation of Cytochrome P450 enzymes (CYPs), P-glycoprotein (P-gp), and Pregnane X receptor (PXR). This study aimed to determine the effects of an EtOH extract, BuOH and CHCl3 fractions and alkaloids of California poppy on the activity of CYPs, P-gp and PXR. The extract and fractions showed strong inhibition of CYP3A4, 2D6, and 2C19 and a weak inhibition of 2C9 and 1A2. Among the alkaloids, escholtzine inhibited 3A4, 2D6 and 2C19 (IC50 3.0, 2.0 and 0.4µM) and protopine inhibited 2D6 and 2C19 (IC50 0.04 and 1.3µM). No inhibition of P-gp was observed with the extract, fractions or its constituents. A significant activation (> 2 fold) of PXR was observed with the extract and fractions (30 µg/mL) while the alkaloids were not as potent (> 1.5 fold at 60µM). Further studies are in progress to find out if the PXR activation would lead to an increased expression of drug metabolizing enzymes and transporters (CYPs and P-gp). Acknowledgement: Supported by the National Institute of General Medical Sciences, NIH Grant Number P20GM104932.