Echinacea and its alkylamides: Effects on the influenza A-induced secretion of cytokines, chemokines, and PGE2 from RAW 264.7 macrophage-like cells

The goal of this study was to determine whether extracts and isolated alkylamides from Echinacea purpurea would be useful for prevention of the inflammatory response that accompanies infections with H1N1 influenza A. Seventeen extracts and 4 alkylamides were tested for the ability to inhibit production of cytokines, chemokines, and PGE2 from RAW 264.7 macrophage-like cells infected with the H1N1 influenza A strain PR/8/34. The alkylamides undeca-2Z,4E-diene-8,10-diynic acid isobutylamide, dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamide, dodeca-2E,4E-dienoic acid isobutylamide, and undeca-2E-ene-8,10-diynoic acid isobutylamide suppressed production of TNF-α and PGE2 from infected cells. Dodeca-2E,4E-dienoic acid isobutylamide was especially effective at inhibiting production of these mediators and also strongly inhibited production of G-CSF, CCL2/MCP-1, CCL3/MIP-1α and CCL5/RANTES. In contrast, the ethanol extracts (75%), which were prepared from dormant roots of E. purpurea grown in different locations throughout North Carolina, displayed a range of effects from suppression to stimulation of mediator production. Precipitation of the extracts with ethanol removed the stimulatory activity, however, even after precipitation; many of the extracts did not display any suppressive activity. Analysis of the extracts revealed slight variations in concentration of alkylamides, caftaric acid, and cichoric acid, but the activity of the extracts did not strongly correlate with concentrations of these compounds. Our in vitro experiments suggest that E. purpurea extracts have the potential for use in alleviating the symptoms and pathology associated with infections with influenza A; however, further study will be necessary to define procedures necessary to unmask the alkylamide activity in crude extracts.

Research highlights► Alkylamides isolated from Echinacea suppress secretion of PGE2 and TNF-α from influenza infected RAW 264.7 macrophage-like cells ► Activity of ethanolic Echinacea purpurea extracts depends greatly on source material and is only moderately correlated with alkylamide content ► Ethanolic Echinacea purpurea extracts (75%) appear to contain unidentified constituents (but not endotoxin) that mask the anti-inflammatory activity of the alkylamide constituents