Alkamides from Echinacea angustifolia roots inhibit Cyclooxygenase-2-dependent Prostaglandin synthesis in Human Neuroglioma Cells

During past years inhibition of the cyclooxygenase-2 (COX-2) enzyme has been proven as an effective strategy to suppress pain and inflammation. Based on this and other mechanistic findings, interest has also renewed in the molecular pathways underlying the anti-inflammatory effects of herbal drugs. The present study addressed this issue and investigated the impact of several polyunsaturated alkamides isolated from a CO₂ extract of the roots of Echinacea angustifolia DC. with both activity and expression of COX-2. Experiments were performed using the human neuroglioma cell line H4, which has been established as a suitable model for studying molecular mechanisms and pathways involved in COX-2 expression [1, 2]. A 48-h treatment of H4 human neuroglioma cells with the CO₂ extract led to a significant downregulation of prostaglandin E₂ formation. Analysis of 8 different alkamides revealed a contribution of undeca 2Z-ene-8,10-diynoic acid isobutylamide (A5), dodeca-2E-ene-8,10-diynoic acid isobutylamide (A7) and dodeca-2E,4Z-diene-8,10-diynoic acid 2-methylbutylamide (A8) to this response. Using an established short-term COX-2 activity assay all three alkamides were shown to interfere with COX-2 activity. In contrast, none of the COX-2-suppressing nor any other tested alkamide was found to inhibit COX-2 expression at the transcriptional and translational level. Overall, our results suggest that certain alkamides derived from Echinacea angustifolia roots may contribute to the pharmacological action of the herbal extract by inhibiting COX-2-dependent prostaglandin E₂ formation at sites of inflammation.

References: 1. Ramer, et al. (2003), Mol. Pharmacol. 324: 621–626. 2. Hinz, B. et al. (2004), Mol. Pharmacol. 64:1189–1198.