Planta Med 2005; 71(8): 701-705
DOI: 10.1055/s-2005-871290
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© Georg Thieme Verlag KG Stuttgart · New York

The Endocannabinoid System as a Target for Alkamides from Echinacea angustifolia Roots

Karin Woelkart1 , Wei Xu2 , Ying Pei2 , Alexandros Makriyannis2 , Robert P. Picone2 , Rudolf Bauer1
  • 1Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Karl-Franzens-University Graz, Graz, Austria
  • 2Center for Drug Discovery, University of Connecticut, CT, USA
Further Information

Publication History

Received: March 29, 2005

Accepted: May 25, 2005

Publication Date:
11 August 2005 (online)

Abstract

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 [³H]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.

Abbreviations

CB1:cannabinoid receptor 1

CB2:cannabinoid receptor 2

FAAH:Fatty acid amidohydrolase

PMSF:phenylmethanesulfonylfluoride

AEA:arachidonylethanolamide, anandamide

AA:arachidonic acid

IL:interleukin

MCP:monocyte chemoattractant protein

BSA:bovine serum albumin

TNF-α:tumor necrosis factor-alpha

MAPK:mitogen-activated protein kinase

JNK:jun N-terminal kinase

cAMP:cyclic adenosine monophosphate

CREB-1:responsive element binding protein-1

ATF-2:activating transcription factor-2

NF-κB:nuclear factor kappa B

Tris:Tris-(hydroxymethyl)-amino-methane

CP55940:(-)-cis-3-[2-hydroxy-4(1,1-dimethyl-heptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol

References

Rudolf Bauer

Institute of Pharmaceutical Sciences

Department of Pharmacognosy

Karl-Franzens-University Graz

Universitätsplatz 4/I

8010 Graz

Austria

Phone: +43-316-380-8700

Fax: +43-316-380-9860

Email: [email protected]