Synergistic immunomopharmacological effects of N-alkylamides in Echinacea purpurea herbal extracts

Int Immunopharmacol. 2009 Jul;9(7-8):850-8. doi: 10.1016/j.intimp.2009.03.006. Epub 2009 Mar 19.


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.

MeSH terms

  • Calcium / metabolism
  • Cannabinoid Receptor Modulators / immunology
  • Cannabinoid Receptor Modulators / metabolism
  • Chromatography, High Pressure Liquid
  • Drug Synergism
  • Echinacea*
  • HL-60 Cells
  • Humans
  • Interleukin-10 / metabolism
  • Neutrophils / drug effects*
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Neutrophils / pathology
  • Phytotherapy*
  • Plant Extracts / analysis
  • Plant Extracts / therapeutic use*
  • Plant Roots
  • Polyunsaturated Alkamides / chemistry
  • Polyunsaturated Alkamides / therapeutic use*
  • Protein Transport
  • Radioligand Assay
  • Receptor, Cannabinoid, CB1 / genetics
  • Receptor, Cannabinoid, CB1 / immunology
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptor, Cannabinoid, CB2 / genetics
  • Receptor, Cannabinoid, CB2 / immunology
  • Receptor, Cannabinoid, CB2 / metabolism
  • Respiratory Tract Infections / drug therapy*
  • Respiratory Tract Infections / immunology
  • Transfection
  • Tumor Necrosis Factor-alpha / metabolism
  • U937 Cells


  • Cannabinoid Receptor Modulators
  • Plant Extracts
  • Polyunsaturated Alkamides
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Calcium