Cichoric acid

In addition to chemotype patterning revealed by statistical analysis of the data, latitudinal relationships emerged as well. Concentrations of cichoric acid and echinacoside and one of the amides, undeca-2Z,4Z-diene-8,10-diynoic acid 2-methylbutyl amide [246], with a larger amine-bearing group increased with latitude. The inverse relationship was observed for caftaric acid and hexadeca-2 , 9Z-diene-12,14-diynoic acid isobutylamide. The latitudinal differences may be of importance in helping to identify populations for selection of seed for propagation. 

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. 

Main actives Water-soluble polysaccharides and glycoproteins, volatile oil (up to 2%), caffeic and ferulic acid derivatives including cichoric acid (0.6-2.1%), alkamides (0.01-0.04%), polyynes and pyrrolizidine alkaloids. 

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. 

Tartaric acid Feruloyl (i.e., ferulic acid) 2,3-O-dicaffeoyltartaric acid (Cichoric Acid) R1, R2 = X 2-0-caffeoyl-3-0-feruloyltartaric acid R1 = X, R2 = Y 2-O-caffeoyltartaric acid (Caftaric acid) R1 = X, R2= H... 

A qualitative determination of the CAP in E. pallida showed that the roots contain high echinacoside levels whereas, cichoric acid was the predominant CAP in the flowers and leaves (Cheminat et al., 1988). This qualitative evaluation is a reasonable approximation of the CAP distribution in plant tissue however, the level of the individual CAP is dictated by the Echinacea species evaluated. Pietta et al. (1998) presented a qualitative evaluation on the CAP in E. purpurea, E. pallida and E. angustifolia using micellar electrokinetic chromatography (MEKC). These authors noted that echinacoside was present in the roots and aerial parts of the E. pallida and E. angustifolia, but not E. purpurea. Cichoric acid is the predominant CAP in E. purpurea roots and aerial parts but is virtually absent in all parts of E. angustifolia and roots of E. pallida. The presence of other CAP in plant tissues is variable and species-variety-dependent (Tables III-V). 

AVERAGE CICHORIC ACID CONTENT (mg/g PLANT PART DRY WEIGHT) OF VARIOUS PLANT PARTS... 

Binns et al. (2002a)—average cichoric acid content for E. purpurea grown under cultivated and wild environments. 

CONTENT1 AND DISTRIBUTION OF CICHORIC ACID IN VARIOUS PLANT TISSUE OF MATURE E. PURPUREA GROWN OVER TWO SEASONS AT DIFFERENT LOCATIONS IN AUSTRALIA... 

Contribution (%) to total cichoric acid/plant by each plant part. 

A 1,2-dihydroxy moiety is a structural feature of molecules susceptible to the enzymatic degradation by polyphenol oxidase (PPO). Cichoric acid contains this structural feature and is thus susceptible to enzymatic degradation (Bauer, 1997). The immunostimulatory activity of Echinacea is partly due to the cichoric acid, and hence protection against enzymatic degradation is critical for retaining the potency of Echinacea preparations. 

Cichoric acid content of six commercially available E. purpurea expressed juice preparations, preserved with ethanol (20%) or by thermal processing, varied significantly between preservation methods (Bauer, 1999b). The thermally treated preparations had an average cichoric acid content of 0.24 g/100 ml of extract. In contrast, the cichoric acid content of the five ethanol preserved preparations was 0.075 g/100 ml extract. Several preparations had no cichoric acid whereas one ethanol-preserved preparation contained 0.14 g cichoric acid/100 ml extract. Within this preparation, the cichoric acid content of several lots varied from 0 to 0.34 g/100 ml extract. Bauer (1999b) hypothesized that the inactivation of PPO by heat may account for the difference in cichoric acid content found between heated and non-heated preparations. Any expressed juice would be expected to contain enzyme inherent to the plant tissue thus, additional processing of the expressed juice preparation is critical for CAP retention. 

FIG. 7 The hydrolysis of the ester bond between the caffeoyl moiety and tartaric acid in cichoric acid (1) to give caftaric (2) and caffeic (3) acids as proposed by Niisslein et al... 

COMPARISON BETWEEN SOXHLET AND ULTRASOUND-PROMOTED EXTRACTION OF CICHORIC ACID AND ECHINACOSIDE FROM E. PURPUREA AND E. ANGUSTIFOLIA, RESPECTIVELY... 

Extraction condition E. angustifolia roots Echinacoside E. purpurea root Cichoric acid E. purpurea top Cichoric acid... 

In contrast to alkamides, alternative extraction solvents such as SF carbon dioxide appear to be ineffective as an extraction solvent for CAP removal (Catchpole et al., 2002 Sun et al., 2002). Conditions evaluated by these researchers include pressures of 31 - 55 MPa and temperatures between 41 and 60°C. In both studies, ethanol was used as a solvent modifier, but the supercritical carbon dioxide was not modified sufficiently to promote the extraction of CAP. The addition of 10% methanol to the supercritical carbon dioxide at 25 MPa and 60°C was sufficient to promote the extraction of rosmarinic acid, a compound with similar structure features as cichoric acid (Bicchi et al., 2000). Thus, additional work is needed to determine if SFE can be used as a method to remove CAP. 

FIG. 8 The effect of temperature on cichoric acid recovery from Echinacea tissue (adapted from Stuart and Wills (2000b)). 

The CAP have been reported to inhibit HIV type 1 (HIV-1) integrase and HIV-1 replications at concentrations as low as 10 p,M (McDougall et al., 1998 King et al., 1999 Reinke et al., 2002). Cichoric acid inhibited 50% of the integrase activity and blocked HIV-1 infections by 50% at concentrations of 0.3 and 4 p,M, respectively (Robinson et al., 1996a,b). Hexane extracts of Echinacea roots were found to have antiviral activity against the Herpes simplex virus type 1 at a 0.12 mg/ml concentration (Binns et al., 2002d). 

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