Synergistic immunomopharmacological effects of N-alkylamides in Echinacea purpurea herbal extracts.
Echinacea purpurea extracts are used in the production of standardized herbal medicines for the prevention and treatment of upper respiratory infections. Unsaturated N-alkylamide lipids, the main constituent of E. purpurea and E. angustifolia preparations capable of activating the cannabinoid receptor type-2 (CB2) have been suggested to play a role as potential anti-inflammatory and immune-modulatory principles. Here we show that ethanolic E. purpurea radix and herba extracts produce synergistic pharmacological effects on the endocannabinoid system in vitro. Superadditive action of N-alkylamide combinations was seen at the level of intracellular calcium release as a function of CB2 receptor activation. Likewise, synergism of the radix and herba tinctures was observed in experiments measuring LPS-stimulated cytokine expression from human PBMCs. While the expression of the anti-inflammatory cytokine IL-10 was significantly superstimulated, the expression of the pro-inflammatory TNF-alpha protein was inhibited more strongly upon combination of the extracts. We show that N-alkylamides act in concert and exert pleiotropic effects modulating the endocannabinoid system by simultaneously targeting the CB2 receptor, endocannabinoid transport and degradation.
Chicca
Andrea
A
ETH Zurich, Department of Chemistry and Applied Biosciences, CH-8093 Zürich, Switzerland.
Raduner
Stefan
S
Pellati
Federica
F
Strompen
Thomas
T
Altmann
Karl-Heinz
KH
Schoop
Roland
R
Gertsch
Jürg
J
D002118:Calcium / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000276:immunology / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004357:Drug Synergism; D020900:Echinacea; D018922:HL-60 Cells; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008517:Phytotherapy; D010936:Plant Extracts / Q000032:analysis / Q000627:therapeutic use*; D018517:Plant Roots; D053284:Polyunsaturated Alkamides / Q000737:chemistry / Q000627:therapeutic use*; D021381:Protein Transport; D011869:Radioligand Assay; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000276:immunology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D020298:U937 Cells
D063385:Cannabinoid Receptor Modulators; D010936:Plant Extracts; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002118:Calcium