Echinacea alkamides

Cannabinomimetic activity. The echinacea alkamides dodeca-2 , 4 , 8Z,10Z-tetraenoic acid isobutylamide and dodeca-2 , 4 -dienoic acid isobutylamide bind more strongly to the human CB2 cannabinoid receptor (Zj 60 uM) than the endogenous cannabinoid anandamide (A i > 200 run). The CB2 binding resulted in inhibition of LPS-induced inflammation in human whole blood." An earlier study with rodent cannabinoid receptors (CBl and CB2) also showed that alkamides from E. angusti-folia roots displayed selective CB2 binding. ... 

Clifford, L.J. et al., Bioactivity of alkamides isolated from Echinacea purpurea (L.) Moench, Phytomedicine, 9, 249, 2002. 

The purple coneflower Echinacea purpura, and its close relatives, E. angustifolia and E. pallida, are the source of the herb Echinacea, which is widely popular as a nonspecific immune stimulant. These perennials are native to the prairies of North America and are now widely grown garden ornamentals. The root and aerial parts of the plant are the portions used, and the preparation s potency can be verified by the transient tingling sensation produced when it is tasted. Echinacea contains alkamides, caffeic acid esters (echinacoside, cichoric acid, caftaric acid), polysaccharides (heteroxylan), and an essential oil. Some echinacea products are standardized for their echinacoside content. In the past, adulteration with American feverfew (Parthenium integri-folium) was common. Echinacea is now sold either by itself or in combination with golden seal or zinc for the treatment of colds and influenza. 

Bauer R, Foster S. Analysis of alkamides and caffeic acid derivatives from Echinacea simulata and E. paradoxa roots. Planta Med 1991 57 447-449. 

The three most widely used species of Echinacea are Echinacea purpurea, E pallida, and E angustifolia. The chemical constituents include flavonoids, lipophilic constituents (eg, alkamides, polyacetylenes), water-soluble polysaccharides, and water-soluble caffeoyl conjugates (eg, echinacoside, chicoric acid, caffeic acid). Within any marketed echinacea formulation, the relative amounts of these components are dependent upon the species used, the method of manufacture, and the plant parts used. Epurpurea has been the most widely studied in clinical trials. Although the active constituents of echinacea are not completely known, chicoric acid from E purpurea and echinacoside from E pallida and E angustifolia, as well as alkamides and polysaccharides, are most often noted as having immune-modulating properties. Most commercial formulations, however, are not standardized for any particular constituent. 

Benefits Echinacea is held to be one of the most effective detoxifying herbs in Western medicine for a range of ailments, and is now used in ayurvedic medicine. The polyynes and cichoric acid components are reported to have antibacterial and virostatic effects. Echinacea also demonstrates an anti-inflammatory effect due to the alkamides component. As an immune stimulant, it significantly raises immunoglobulin M levels. Antiviral activities against both the Herpes simplex virus Type I and the influenza-A virus have been observed. 

Perry NB, van Klink JW, Burgess EJ and Par-menter GA (1997) Alkamide levels in Echinacea purpurea a rapid analytical method revealing differences among roots, rhizomes, stems, leaves and flowers. Planta Med 63, 58-62. 

The three most widely used species of Echinacea are Echinacea purpurea, Epallida, and E angustifolia. The chemical constituents include flavonoids, lipophilic constituents (eg, alkamides,... 

FIG. 1 Alkamides and ketoalkenes/alkynes identified in Echinacea. Numbers in parentheses refer to the numbers assigned by Bauer and Remiger (1989). 

AVERAGE TOTAL ALKAMIDE" CONTENT (mg/g DRY ROOT) OF VARIOUS ECHINACEA SPECIES AND VARIETIES GROWN UNDER CULTIVATED AND WILD ENVIRONMENTS... 

Bauer (1999b) found that the alkamide, dodeca-2 ,4E,8Z, 1 OE/Z-tetra-enoic acid isobutylamide, level was influenced by the preparation method. Nonthermal preparations appeared to have slightly higher levels of the tested alkamide than thermally treated products. Thus, the drying process may not be the best method for preparing Echinacea products. Pressing of the plant material to obtain an expressed juice is a common preparation method however, preservation of the juice with ethanol is required. Direct ethanol extraction of the plant material can be used in place of the pressing operation. 

FIG. 5 The effect of ethanol concentration on alkamide recovery from Echinacea tissue (adapted from Stuart and Wills (2000b)). 

Stuart and Wills (2000b) reported a decrease, from 60 to 15%, in alkamide content of extracts prepared from Echinacea root with increasing particle size, from 300 to 4000 xm. Particle size is also important in SF extractions as noted by Sun et al. (2002). These authors noted a 10-fold increase in alkamide extraction simply due to grinding the sample. 

In general, polysaccharides tend to be more stable than alkamides and CAP, but their presence in Echinacea preparations is somewhat dictated by processing conditions. For example, one would expect dried plant material to contain the highest polysaccharide levels, followed by expressed juice preparation and alcohol tincture. Limited data are available regarding the effects of post-harvest handling and processing on polysaccharide levels. 

The in vitro antifungal activity of the lipophilic extracts and commercial tinctures of Echinacea was enhanced after exposure to UV irradiation (Binns et al, 2000). These authors noted that E. purpurea flowers and a commercial tea product were the only products that lacked antifungal activity after UV exposure. The photooxidation of the alkamide, ketoalkenes and ketoalkynes contributed to the enhanced antifungal activity (Binns et al., 2000). 

Echinacea has been used for centuries as a medicinal plant and has been promoted recently as an immunostimulant. Research from the last two decades has shown that Echinacea can enhance the immune system using in vitro and in vivo indicators. Jager et al. (2002) reported that dodeca-2E,4 , 8Z,10 yZ-tetraenoic acid isobutylamides could cross biological barriers via passive diffusion, suggesting that the alkamides may contribute to the in vivo effects noted by researchers. In contrast, conflicting results have... 

Bauer, R. 1997. Standardisierung von Echinacea purpurea-Pre saft auf cichoriensaure und alkamide. 

Bauer, R. 1999b. Standardization of Echinacea purpurea expressed juice with reference to cichoric acid and alkamides. J. Herbs Spices Med. Plants 6, 51—61. 

Bauer, R. and Remiger, P. 1989. TLC and HPLC analysis of alkamides in Echinacea drugs. Planta Med. 55, 367-371. 

Bauer, R., Remiger, P., and Wagner, H. 1988c. Alkamides from the roots of Echinacea purpurea. Phytochemistry 27, 2339-2342. 

He, X., Lin, L., Bernart, M.W., and Lian, L. 1998. Analysis of alkamides in roots and achenes of Echinacea purpurea by liquid chromatography-electrospray mass spectrometry. J. Chromatogr. A 815, 205-211. 

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