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ARS Home » Southeast Area » Oxford, Mississippi » Natural Products Utilization Research » Research » Publications at this Location » Publication #325352
Research Project: Discovery and Development of Natural Products for Pharmaceutical and Agrochemical Applications II

Location: Natural Products Utilization Research

Title: Modulation of CYPs, P-gp, and PXR by Eschscholzia californica (California poppy) and its alkaloids

Author
item MANDA, VAMSHI - University Of Mississippi
item IBRAHIM, MOHAMED - University Of Mississippi
item DALE, OLIVIA - University Of Mississippi
item KUMARIHAMY, MALLIKA - University Of Mississippi
item CUTLER, STEPHEN - Egypt National Research Center
item KHAN, IKHLAS - University Of Mississippi
item WALKER, LARRY - University Of Mississippi
item MUHAMMAD, ILIAS - University Of Mississippi
item KHAN, SHABANA - University Of Mississippi

Submitted to: Planta Medica
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/13/2016
Publication Date: 4/7/2016
Publication URL: http://handle.nal.usda.gov/10113/62425
Citation: Manda, V.K., Ibrahim, M.A., Dale, O.R., Kumarihamy, M., Cutler, S.J., Khan, I.A., Walker, L.A., Muhammad, I., Khan, S.I. 2016. Modulation of CYPs, P-gp, and PXR by Eschscholzia californica (California poppy) and its alkaloids. Planta Medica. 82:551-558. DOI http://dx.doi.org/10.1055/s-0042-103689

Interpretive Summary: Eschscholzia californica Cham. (Fam. Papaveraceae), popularly known as California poppy, is distributed throughout the Western part of United States, including California, Oregon and Washington. This plant is traditionally used to treat anxiety, pain and insomnia. Despite the use of California poppy as an herbal supplement, there are no reports available to determine if it interacts with any over the counter or prescription medicines. This study has shown that California poppy extract and its isolated constituents have potential to cause interactions with drugs that are metabolized by enzymes present in the liver.

Technical Abstract: Eschscholzia californica Cham., a native US plant, is traditionally used as a sedative, analgesic and anxiolytic herb. With the rapid rise in the use of herbal supplements together with over the counter (OTC) and prescription 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) by concomitantly used herbs. This study was aimed to determine the effects of an EtOH extract, BuOH extract, aqueous extract (tea), acidic and basic CHCl3 partitions and isolated alkaloids, namely protopine (1), escholtzine (2), allocryptopine (3) and californidine (4), of E. californica on the activity of CYPs, P-gp and PXR. The extracts and partitions showed strong time dependent inhibition of CYP3A4, CYP2C9, and CYP2C19 and reversible inhibition of CYP2D6. Among the alkaloids, escholtzine (2) and allocryptopine (3) exhibited time dependent inhibition of CYP3A4, CYP2C9 and CYP2C19 (IC50 shift ratio > 2). Both protopine (1) and allocryptopine (3) were also found to be potent reversible inhibitors of CYP2D6, while the latter demonstrated time dependent inhibition of CYP2C19, but no effect on CYP3A4 and CYP2C9. A significant activation of PXR (> 2 fold) was observed with the extract, partitions, and alkaloids (except protopine) which resulted into an increased expression of mRNA and the activity of CYP3A4 and CYP1A2. The expression of P-gp was unaffected. However, tea and its main alkaloid californidine (4) did not affect CYPs, P-gp or PXR. This data suggests that E. californica extract and its major alkaloids have a potential of causing interactions with drugs, which are metabolized by CYPs, while the tea seems to be safer.