title: Liver enzyme-mediated oxidation of Echinacea purpurea alkylamides: production of novel metabolites and changes in immunomodulatory activity.
abstract: The medicinal plant Echinacea is widely used to treat upper respiratory infections and is reported to stimulate the human immune system. A major constituent class of Echinacea, the alkylamides, has immunomodulatory effects. Recent studies show that alkylamides are oxidized by cytochrome P450 enzymes, but the immunomodulatory activity of these products is unknown. The objectives of this study were to characterize the products formed by incubation of an Echinacea extract and an isolated alkylamide with human liver microsomes, and to evaluate the influence of Echinacea alkylamides and metabolites on cytokine production by Jurkat human T cells. A novel class of carboxylic acid alkylamide metabolites was identified and shown to be the major constituents present after 2-h incubation of alkylamides with human liver microsomes. Echinacea alkylamides suppressed IL-2 secretion by stimulated T cells, and this effect was significantly lessened upon oxidation of the alkylamides to carboxylic acids and hydroxylated metabolites. These findings highlight the importance of considering the influence of liver enzyme metabolism when evaluating the immunomodulatory effects of alkylamides.
authors.affiliation: Department of Chemistry and Biochemistry, The University of North Carolina Greensboro, Greensboro, NC 27402, USA. nadja_cech@uncg.edu
authors.forename: Nadja B
authors.initials: NB
authors.lastname: Cech
authors.forename: Katrina
authors.initials: K
authors.lastname: Tutor
authors.forename: Bethany A
authors.initials: BA
authors.lastname: Doty
authors.forename: Kevin
authors.initials: K
authors.lastname: Spelman
authors.forename: Masa
authors.initials: M
authors.lastname: Sasagawa
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Raner
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Wenner
mesh_terms: D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D020900:Echinacea; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007376:Interleukin-2 / Q000378:metabolism*; D019169:Jurkat Cells; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010084:Oxidation-Reduction; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D053284:Polyunsaturated Alkamides / Q000737:chemistry
chemical_list: D007155:Immunologic Factors; D007376:Interleukin-2; D010936:Plant Extracts; D053284:Polyunsaturated Alkamides