Alkamides from Echinacea and Cannabinoid Receptors
If you asked someone to name an immune-boosting botanical, chances are, they’d say “Echinacea.” And they’d be right. But Echinacea does more than stop colds and flus. It provides natural compounds called “alkamides”, which are bind to cannabinoid receptors in the body and help relieve anxiety in addition to immune system stimulating effects.
As our understanding of the endocannabinoid system has developed over the past 25 years, so too has our knowledge of how many natural compounds interact with that system. Alkamides from Echinacea would not necessarily be top of mind when talking about interactions with the endocannabinoid system – hemp generally fits that role. But as we learn more about cannabinoids and closely related natural compounds, there will be more surprises along way that illustrate the complexity of natural medicines.
Woelkart K, Bauer R. The role of alkamides as an active principle of echinacea. Planta Med. 2007 Jun;73(7):615-23. Epub 2007 May 31.
Alkamides are the major lipophilic constituents of ECHINACEA preparations, which are widely used in some European countries and in North America for common colds. In earlier investigations they have been shown to possess stimulatory effects on phagocytosis. Recent experiments have demonstrated that alkamides are detectable in human blood in relevant concentrations after oral administration of Echinacea preparations. Alkamides show structural similarity with anandamide, an endogenous ligand of cannabinoid receptors. Consequently, it was found that alkamides bind significantly to CB (2) receptors, which is now considered as a possible molecular mode of action of Echinacea alkamides as immunomodulatory agents. It was also demonstrated recently in several studies that alkamide-containing Echinacea preparations trigger effects on the pro-inflammatory cytokines. They were therefore suggested as a new class of cannabinomimetics. However, the therapeutic relevance of these findings is still not clear as clinical studies on the common cold show contradictory results. Among the many pharmacological properties reported, investigations concerning herb-drug interactions have been neglected for a long time. Latest research concludes that prolonged use of Echinacea poses a minimal risk for co-medications metabolized by the P450 enzymes.
Woelkart K, Xu W, Pei Y, Makriyannis A, Picone RP, Bauer R. The endocannabinoid system as a target for alkamides from Echinacea angustifolia roots. Planta Med. 2005 Aug;71(8):701-5.
Alkamides are the major lipophilic constituents of Echinacea angustifolia roots. Due to their structural similarity with anandamide, we have evaluated their ability to bind to rodent cannabinoid receptors CB1 and CB2 by a standard receptor binding assay using [(3)H]CP-55,940 as a radioligand. The alkamides exhibited selective affinity especially to CB2 receptors and can therefore be considered as CB ligands. Most of the alkamides showed good metabolic stability as indicated by the similarity between affinity to CB1 determined in the presence/absence of the protease inhibitor PMSF. It is suggested that CB2 interactions may be the molecular mode of action of Echinacea alkamides as immunomodulators.
Hohmann J, et al. Alkamides and a neolignan from Echinacea purpurea roots and the interaction of alkamides with G-protein-coupled cannabinoid receptors. Phytochemistry 2011 Oct;72(14-15):1848-53.
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 the spices. Additionally, 10 known Echinacea 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 the [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.