Isolation, structure determination and cannabinoid receptor activating effect of new metabolites of Echinacea purpurea root

Extracts of Echinacea purpurea are extensively used in the therapy of common cold and upper respiratory tract infections as immunomodulators and anti-inflammatory agents. The extracts of the root and herb of E. purpurea have a complex chemical composition, including alkamides, caffeic acid conjugates, and polysaccharides. Alkamides, the main lipophilic compounds, are the modulators of the endocannabinoid system in consequence of their structural similarity to the endogenous ligand anandamide. Recently, receptor binding assays demonstrated the CB2 receptor affinity of Echinacea alkamides, proving by this the CB2-receptor-dependent immunomodulatory effect [1,2]. The aim of the present study was to reinvestigate the chemical composition of the roots of E. purpurea and to gain new information about the affinity of the isolated compounds to the cannabinoid system. The nhexane-soluble extract of the root was subjected to multiple chromatographic separations affording 19 compounds. The structures were analysed by extensive NMR and MS studies resulting the identification of four new natural products (3 alkamides and nitidanin-diisovalerianate). In addition, five compounds were detected for the first time in this species, and ten known E. purpurea metabolites were identified. Cannabinoid receptor activation of thirteen isolated compounds has been studied by [³⁵S]GTPγS binding assays in rat brain membranes. This test measures (i) receptor-mediated G-protein activation induced by agonists and (ii) inhibition by antagonist ligands. A number of E. purpurea compounds turned out to be weak-to-moderate partial agonists, while others displayed inverse-agonist actions. In the presence of a reference CB1 receptor agonist, both sort of compounds exhibited concentration-dependent competitive antagonist effects.

References: 1. Woelkart, K., Bauer, R. (2007) Planta Med. 73:615–623.

2. Raduner, S., et al. (2006)J. Biol. Chem. 281:14192–14206.