The results of this study indicate that extracts of E. angustifolia root, either alone or in combination, do not have clinically significant effects on infection with a rhinovirus or on the clinical illness that results from it.
IntroductionEchinacea preparations represent the most common herbal immunomodulators. They are marketed mainly for the treatment and prevention of the common cold and other upper respiratory tract infections (URTIs). An analysis reveals that completely different preparations are sold under the name Echinacea using different plant parts and different extraction solvents. The most abundantly used species are Echinacea angustifolia, Echinacea purpurea and Echinacea pallida [1]. Several reviews on the effectiveness of orally ingested Echinacea extracts in reducing the incidence, severity, or duration of acute URTIs have been published. The majority of trials investigated whether Echinacea preparations shorten the duration or decrease the severity of symptoms of the common cold (for reviews see AbstractAlkamides are the major lipophilic constituents of Echinacea preparations, which are widely used in some European countries and in North America for common colds. In earlier investigations they have been shown to possess stimulatory effects on phagocytosis. Recent experiments have demonstrated that alkamides are detectable in human blood in relevant concentrations after oral administration of Echinacea preparations. Alkamides show structural similarity with anandamide, an endogenous ligand of cannabinoid receptors. Consequently, it was found that alkamides bind significantly to CB 2 receptors, which is now considered as a possible molecular mode of action of Echinacea alkamides as immunomodulatory agents. It was also demonstrated recently in several studies that alkamide-containing Echinacea preparations trigger effects on the pro-inflammatory cytokines. They were therefore suggested as a new class of cannabinomimetics. However, the therapeutic relevance of these findings is still not clear as clinical studies on the common cold show contradictory results. Among the many pharmacological properties reported, investigations concerning herb-drug interactions have been neglected for a long time. Latest research concludes that prolonged use of Echinacea poses a minimal risk for co-medications metabolized by the P450 enzymes. Key wordsAlkamides´Echinacea purpurea´Echinacea angustifolia´Astera-ceae´immunomodulation´pharmacokinetics´cannabinoid receptor binding´herb-drug interactions Supporting information available online at
Alkamides are the major lipophilic constituents of Echinacea angustifolia roots. Due to their structural similarity with anandamide, we have evaluated their ability to bind to rodent cannabinoid receptors CB1 and CB2 by a standard receptor binding assay using [(3)H]CP-55,940 as a radioligand. The alkamides exhibited selective affinity especially to CB2 receptors and can therefore be considered as CB ligands. Most of the alkamides showed good metabolic stability as indicated by the similarity between affinity to CB1 determined in the presence/absence of the protease inhibitor PMSF. It is suggested that CB2 interactions may be the molecular mode of action of Echinacea alkamides as immunomodulators.
Alkamides are suspected to contribute to the activity of Echinacea preparations. They are mainly derived from undeca- and dodecanoic acid and differ in the degree of unsaturation and the configuration of the double bonds. In total, 6 alkamides have been isolated from the roots of Echinacea angustifolia as major lipophilic constituents and have been investigated regarding their pharmacokinetics. A sensitive and specific method has been developed for the identification and quantification of these alkamides in human plasma using liquid chromatography electrospray ionization ion-trap mass spectrometry. The method was applied to analyze plasma samples obtained from a randomized, open, single-dose, crossover study after oral administration of a 60% ethanolic extract from the roots of E. angustifolia to 11 healthy subjects. The maximum concentration of dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides, the main alkamides in the roots of E. angustifolia, appeared already after 30 minutes and was 10.88 ng/mL for the 2.5-mL dose.
Analysis 1.3. Comparison 1 Echinacea versus placebo to prevent common cold, Outcome 3 Duration: mean difference. Analysis 1.4. Comparison 1 Echinacea versus placebo to prevent common cold, Outcome 4 Total severity score.. . Analysis 1.5. Comparison 1 Echinacea versus placebo to prevent common cold, Outcome 5 Number of patients dropping
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