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Echinacea alkylamides modulate TNF-alpha gene expression via cannabinoid receptor CB2 and multiple signal transduction pathways.
FEBS Lett. 2004 Nov 19; 577(3):563-9.FL

Abstract

Echinacea plant preparations are widely used in the prevention and treatment of common cold. However, so far no molecular mechanism of action has been proposed. We analyzed the standardized tincture Echinaforce and found that it induced de novo synthesis of tumor necrosis factor alpha (TNF-alpha) mRNA in primary human monocytes/macrophages, but not TNF-alpha protein. Moreover, LPS-stimulated TNF-alpha protein was potently inhibited in the early phase but prolonged in the late phase. A study of the main constituents of the extract showed that the alkylamides dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides (1/2), trienoic (3) and dienoic acid (4) derivatives are responsible for this effect. The upregulation of TNF-alpha mRNA was found to be mediated by CB2 receptors, increased cAMP, p38/MAPK and JNK signaling, as well as NF-kappaB and ATF-2/CREB-1 activation. This study is the first to report a possible molecular mechanism of action of Echinacea, highlighting the role of alkylamides as potent immunomodulators and potential ligands for CB2 receptors.

Authors+Show Affiliations

Swiss Federal Institute of Technology, Institute of Pharmaceutical Sciences, Wolfgang-Pauli-Str. 10 CH-8093 Zürich, Switzerland. juerg.gertsch@pharma.ethz.chNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15556647

Citation

Gertsch, Juerg, et al. "Echinacea Alkylamides Modulate TNF-alpha Gene Expression Via Cannabinoid Receptor CB2 and Multiple Signal Transduction Pathways." FEBS Letters, vol. 577, no. 3, 2004, pp. 563-9.
Gertsch J, Schoop R, Kuenzle U, et al. Echinacea alkylamides modulate TNF-alpha gene expression via cannabinoid receptor CB2 and multiple signal transduction pathways. FEBS Lett. 2004;577(3):563-9.
Gertsch, J., Schoop, R., Kuenzle, U., & Suter, A. (2004). Echinacea alkylamides modulate TNF-alpha gene expression via cannabinoid receptor CB2 and multiple signal transduction pathways. FEBS Letters, 577(3), 563-9.
Gertsch J, et al. Echinacea Alkylamides Modulate TNF-alpha Gene Expression Via Cannabinoid Receptor CB2 and Multiple Signal Transduction Pathways. FEBS Lett. 2004 Nov 19;577(3):563-9. PubMed PMID: 15556647.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Echinacea alkylamides modulate TNF-alpha gene expression via cannabinoid receptor CB2 and multiple signal transduction pathways. AU - Gertsch,Juerg, AU - Schoop,Roland, AU - Kuenzle,Urs, AU - Suter,Andy, PY - 2004/07/30/received PY - 2004/09/22/revised PY - 2004/10/20/accepted PY - 2004/11/24/pubmed PY - 2005/1/14/medline PY - 2004/11/24/entrez SP - 563 EP - 9 JF - FEBS letters JO - FEBS Lett VL - 577 IS - 3 N2 - Echinacea plant preparations are widely used in the prevention and treatment of common cold. However, so far no molecular mechanism of action has been proposed. We analyzed the standardized tincture Echinaforce and found that it induced de novo synthesis of tumor necrosis factor alpha (TNF-alpha) mRNA in primary human monocytes/macrophages, but not TNF-alpha protein. Moreover, LPS-stimulated TNF-alpha protein was potently inhibited in the early phase but prolonged in the late phase. A study of the main constituents of the extract showed that the alkylamides dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides (1/2), trienoic (3) and dienoic acid (4) derivatives are responsible for this effect. The upregulation of TNF-alpha mRNA was found to be mediated by CB2 receptors, increased cAMP, p38/MAPK and JNK signaling, as well as NF-kappaB and ATF-2/CREB-1 activation. This study is the first to report a possible molecular mechanism of action of Echinacea, highlighting the role of alkylamides as potent immunomodulators and potential ligands for CB2 receptors. SN - 0014-5793 UR - https://www.unboundmedicine.com/medline/citation/15556647/Echinacea_alkylamides_modulate_TNF_alpha_gene_expression_via_cannabinoid_receptor_CB2_and_multiple_signal_transduction_pathways_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014579304013183 DB - PRIME DP - Unbound Medicine ER -