title: Alkamides and a neolignan from Echinacea purpurea roots and the interaction of alkamides with G-protein-coupled cannabinoid receptors.
abstract: Multiple chromatographic separations of the CHCl₃-soluble extract of the roots of Echinacea purpurea led to the isolation of 19 compounds. Four natural products, three alkamides and nitidanin diisovalerianate, were identified, and five further compounds were detected for the first time in this species. Additionally, 10 known E. purpurea metabolites were isolated. The structures were determined by mass spectrometry and advanced 1D and 2D NMR techniques. The bioactivity of the isolated compounds was studied in [³⁵S]GTPγS-binding experiments performed on rat brain membrane preparations. Both partial and inverse agonist compounds for cannabinoid (CB1) receptors were identified among the metabolites, characterized by weak to moderate interactions with the G-protein signaling mechanisms. The G-protein-modulating activities of the Echinacea compounds are rather far from the full agonist effects seen with the CB1 receptor agonist reference compound arachidonyl-2'-chloroethylamide (ACEA). However, upon coadministration with ACEA, a number of them proved capable of inhibiting the stimulation of the pure agonist, thereby demonstrating cannabinoid receptor antagonist properties.
authors.affiliation: Department of Pharmacognosy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary. hohmann@pharm.u-szeged.hu
authors.forename: Judit
authors.initials: J
authors.lastname: Hohmann
authors.forename: Dóra
authors.initials: D
authors.lastname: Rédei
authors.forename: Peter
authors.initials: P
authors.lastname: Forgo
authors.forename: Pál
authors.initials: P
authors.lastname: Szabó
authors.forename: Tamás F
authors.initials: TF
authors.lastname: Freund
authors.forename: József
authors.initials: J
authors.lastname: Haller
authors.forename: Engin
authors.initials: E
authors.lastname: Bojnik
authors.forename: Sándor
authors.initials: S
authors.lastname: Benyhe
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002186:Cannabinoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D020900:Echinacea / Q000737:chemistry*; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D053284:Polyunsaturated Alkamides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001095:Arachidonic Acids; D002186:Cannabinoids; D017705:Lignans; D010936:Plant Extracts; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D012717:Sesquiterpenes; C119325:arachidonyl-2-chloroethylamide