Echinacea Species and Alkamides Inhibit Prostaglandin E₂ Production in RAW264.7 Mouse Macrophage Cells

Abstract

Inhibition of prostaglandin E 2 (PGE 2 ) production in lipopolysaccharide-stimulated RAW264.7 mouse macrophage cells was assessed with an enzyme immunoassay following treatments with Echinacea extracts or synthesized alkamides. Results indicated that ethanol extracts diluted in media to a concentration of 15 μg/ mL from E. angustifolia, E. pallida, E. simulata, and E. sanguinea significantly inhibited PGE 2 production. In further studies, PGE 2 production was significantly reduced by all synthesized alkamides assayed at 50 μM, by Bauer alkamides 8, 12A analogue, and 14, Chen alkamide 2, and Chen alkamide 2 analogue at 25 μM and by Bauer alkamide 14 at 10 μM. Cytotoxicity did not play a role in the noted reduction of PGE 2 production in either the Echinacea extracts or synthesized alkamides. High-performance liquid chromatography analysis identified individual alkamides present at concentrations below 2.8 μM in the extracts from the six Echinacea species (15 μg/mL crude extract). Because active extracts contained 2, it is likely that alkamides may contribute toward the anti-inflammatory activity of Echinacea in a synergistic or additive manner.

Alkamid database: Chemistry, occurrence and functionality of plant N-alkylamides

“…It is noteworthy that the synergistic action of NAAs has been demonstrated in numerous studies involving different antiinflammatory pathways (PGE2/5-HPETE/cytokine levels, NF-kB activity, CB2 activation) (Chicca et al, 2009;Lalone et al, 2007;Matthias et al, 2008Matthias et al, , 2007Mullerjakic et al, 1994;Woelkart et al, 2006). This again indicates the importance of the knowledge of phytochemical components present in an investigated and/or used extract.…”

“…At higher concentrations i.e. from 12.5 mg/mL, also NAAs containing double bonds in their acid chain have an inhibitory effect on the COX proinflammatory PGE2 product (23% up to 90% inhibition) (Cech et al, 2010;Hinz et al, 2007;Lalone et al, 2007;Mullerjakic et al, 1994). In the fatty acid part of the NAA, the 2E configuration shows a higher inhibitory effect than the 2Z configuration, (e.g.…”

Echinacea purpurea Extract Affects the Immune System, Global Metabolome, and Gut Microbiome in Wistar Rats

“…Echinacea purpurea Moench (E. purpurea) is an indigenous medicine of the native American Indians and Europeans with multiple biological activities, such as anti-inflammation, anti-oxidation, anti-bacteria, antiproliferative, antihypertensive and immunomodulation effects for hundreds of years (Aarland et al, 2017;Chiou et al, 2017;LaLone et al, 2007). This medicinal plant was also used as food supplements in infectious diseases in children, old people and animals in North America and Europe (Ayrle et al, 2016).…”

Analgesic activity ofHeliopsis longipesand its effect on the nervous system

“…A possible action of the treatments is that these chemical mediators are altered. In this respect, affinin is an alkamide, and it has been found that alkamides can inhibit the production of PGEs (Prostaglandins) (LaLone et al, 2007). Given that the abdominal contraction relates to the sensitization of prostaglandin-nociceptive receptors and of sympathetic nervous system mediators, it is likely that affinin and the ethanol extract inhibit either their synthesis or the contact with their receptors, thereby producing the analgesic effect.…”