<i>Echinacea</i> alkylamides modulate TNF‐α gene expression via cannabinoid receptor CB2 and multiple signal transduction pathways

Gertsch, Jürg; Schoop, Roland; Kuenzle, Urs; Suter, Andy

doi:10.1016/j.febslet.2004.10.064

Cited by 186 publications

(173 citation statements)

References 32 publications

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“…Consequently, it is not surprising that the effects of the different Echinacea species on IL-1β and TNF-α were similar. Our findings that Echinacea tinctures augmented production of these cytokines are consistent with reports from both human (Barak et al 2002;Gertsch et al 2004;Randolph et al 2003) and rodent (Bodinet et al 2002;Luettig et al 1989;Rininger et al 2000;Stimpel et al 1984) model systems; however, two teams found no effect of Echinacea extracts on these cytokines (Elsasser-Beile et al 1996;Schwarz et al 2002). These differences may be due to species selection, plant organ selection, extraction method, or other experimental choices as discussed above.…”

Section: Consideration Of Original Datasupporting

confidence: 92%

Phenetic Comparison of Seven Echinacea Species Based on Immunomodulatory Characteristics

et al. 2006

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The purpose of the present investigation was to compare similarities and differences in immune response among Echinacea species, which are commonly used to treat upper respiratory infections. The investigation involved two components: acquisition of immunomodulatory data reported here for the first time, and combined phenetic analysis of these data along with previous reports. Experimental data were obtained by stimulating human PBMC in vitro with extracts from Echinacea spp. and assaying production of three cytokines (interleukin-1β [IL-1β], interleukin-2 [IL-2], and tumor necrosis factor-α [TNF-α]). Phenetic analyses were employed to compare responses across the entire data set, including UPGMA (Unweighted Pair Group Method with Arithmetic Mean) and neighbor-joining methods. In the immune experiments conducted for this investigation, E. angustifolia, E. paradoxa, E. purpurea, E. simulata, and E. tennesseensis extracts significantly augmented IL-1 β and TNF-α production, whereas no extracts significantly modulated IL-2. All phenetic methods produced similar dendrograms, revealing two species pairs (E. angustifolia + E. simulata and E. pallida + E.sanguinea) where both species cluster tightly and have similar immune-response profiles. These two species-pairs are maximally dissimilar from each other. The remaining species (E. paradoxa, E. purpurea, and E. tennesseensis) occupy intermediate positions in the dendrogram. Our results suggest that Echinacea spp. act heterogeneously on immune function. The utility of these data for science and industry is discussed.

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Section: Consideration Of Original Datasupporting

confidence: 92%

Phenetic Comparison of Seven Echinacea Species Based on Immunomodulatory Characteristics

et al. 2006

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“…The acetylenic fatty acyl groups vary in length from C 9 to C 18 . Extracts of the purple coneflower (Echinacea purpurea) have insecticidal, immunesystem-stimulating, and anti-inflammatory properties that are attributed to the acylamides [192]. Alkamides have been shown to affect root growth and morphology in Arabidopsis indicating a potential role in development [193].…”

Section: 34mentioning

confidence: 99%

Biosynthesis and function of polyacetylenes and allied natural products

Minto

Blacklock

2008

Progress in Lipid Research

290

228

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Polyacetylenic natural products are a substantial class of often unstable compounds containing a unique carbon-carbon triple bond functionality, that are intriguing for their wide variety of biochemical and ecological functions, economic potential, and surprising mode of biosynthesis. Isotopic tracer experiments between 1960 and 1990 demonstrated that the majority of these compounds are derived from fatty acid and polyketide precursors. During the past decade, research into the metabolism of polyacetylenes has swiftly advanced, driven by the cloning of the first genes responsible for polyacetylene biosynthesis in plants, moss, fungi, and actinomycetes, and the initial characterization of the gene products.The current state of knowledge of the biochemistry and molecular genetics of polyacetylenic secondary metabolic pathways will be presented together with an up-to-date survey of new terrestrial and marine natural products, their known biological activities, and a discussion of their likely metabolic origins.

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“…For cytokine measurements, the plates were centrifuged, and an appropriate amount (usually 50 ml) of the supernatant serum was removed for immediate analysis. Isolation of PBMCs and T lymphocytes from peripheral whole blood was performed, as previously reported (39). Cell cultures.…”

Section: Plant Materialsmentioning

confidence: 99%

Ginger Phenylpropanoids Inhibit IL-1β and Prostanoid Secretion and Disrupt Arachidonate-Phospholipid Remodeling by Targeting Phospholipases A2

Nievergelt

Marazzi

Schoop³

et al. 2011

The Journal of Immunology

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The rhizome of ginger (Zingiber officinale) is employed in Asian traditional medicine to treat mild forms of rheumatoid arthritis and fever. We have profiled ginger constituents for robust effects on proinflammatory signaling and cytokine expression in a validated assay using human whole blood. Independent of the stimulus used (LPS, PMA, anti-CD28 Ab, anti-CD3 Ab, and thapsigargin), ginger constituents potently and specifically inhibited IL-1β expression in monocytes/macrophages. Both the calcium-independent phospholipase A2 (iPLA2)-triggered maturation and the cytosolic phospholipase A2 (cPLA2)-dependent secretion of IL-1β from isolated human monocytes were inhibited. In a fluorescence-coupled PLA2 assay, most major ginger phenylpropanoids directly inhibited i/cPLA2 from U937 macrophages, but not hog pancreas secretory phospholipase A2. The effects of the ginger constituents were additive and the potency comparable to the mechanism-based inhibitor bromoenol lactone for iPLA2 and methyl arachidonyl fluorophosphonate for cPLA2, with 10-gingerol/-shogaol being most effective. Furthermore, a ginger extract (2 μg/ml) and 10-shogaol (2 μM) potently inhibited the release of PGE2 and thromboxane B2 (>50%) and partially also leukotriene B4 in LPS-stimulated macrophages. Intriguingly, the total cellular arachidonic acid was increased 2- to 3-fold in U937 cells under all experimental conditions. Our data show that the concurrent inhibition of iPLA2 and prostanoid production causes an accumulation of free intracellular arachidonic acid by disrupting the phospholipid deacylation-reacylation cycle. The inhibition of i/cPLA2, the resulting attenuation of IL-1β secretion, and the simultaneous inhibition of prostanoid production by common ginger phenylpropanoids uncover a new anti-inflammatory molecular mechanism of dietary ginger that may be exploited therapeutically.

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Echinacea alkylamides modulate TNF‐α gene expression via cannabinoid receptor CB2 and multiple signal transduction pathways

Cited by 186 publications

References 32 publications

Phenetic Comparison of Seven Echinacea Species Based on Immunomodulatory Characteristics

Phenetic Comparison of Seven Echinacea Species Based on Immunomodulatory Characteristics

Biosynthesis and function of polyacetylenes and allied natural products

Ginger Phenylpropanoids Inhibit IL-1β and Prostanoid Secretion and Disrupt Arachidonate-Phospholipid Remodeling by Targeting Phospholipases A2

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