Echinacea

Echinacea is part of the daisy family found throughout North America. There are nine species of Echinacea in total and the medicinal preparations are derived from three of these: Echinacea purpurea (purple coneflower), Echinacea pallida (pale purple coneflower), and Echinacea angustifolia (narrow leaved coneflower) (Ness et al. 1999, Bauer and Khan 1985, Melchart et al. 1998). Echinacea is recommended as a prophylactic and treatment substance for upper respiratory infections. However, data are insufficient at present to support the former (Hughes et al. 2004). It has alkylamide and polysaccharide substance which possess significant in vitro and in vivo immunostimulation properties due to enhanced phagocytosis and nonspecific T-cell stimulation (Grimm and Muller 1999).

The consumption of Echinacea at the onset of symptoms has been clinically shown to decrease both the severity and duration of the cold and flu. Employing quantitative polymerase chain reaction (PCR) to identify in vivo alterations in the expression of immunomodulatory genes in response to Echinacea has been performed (Randolph et al. 2003). Investigations conducted on in vivo gene expression within peripheral leukocytes were evaluated in six healthy non-smoking subjects. Blood samples were obtained at baseline and on subsequent days following consumption of a commercially blended Echinacea product. The overall gene expression pattern between 48 h and 12 days after taking Echinacea was consistent with an antiinflammatory response. The expression of interleukin-1^, intracellular adhesion molecule, tumor necrosis factor-a, and interleukin-8 was modestly depressed up through day 5 and returned to baseline by day 12. Further, the expression of interferon-a consistently increased through day 12, thus indicating an antiviral response. Therefore, initial data yielded a gene expression response pattern consistent with the ability of Echinacea to decrease both the intensity and duration of cold and flu symptoms (Randolph et al. 2003).

Aside from the effects of Echinacea on innate immunity, few studies are available that have examined the ability for enhancement of humoral immunity. Although, a study using female Swiss mice as the model found support for the use of E. purpurea, as suggested by anecdotal reports, and demonstrated potential enhancement of humoral immune responses, in addition to innate immune responses (Freier et al. 2003). However, it is important to note that the use of E. purpurea, as dosed in one study, was not effective in treating upper respiratory tract infections and related symptoms in pediatric patients, aged 2-11. Further, the consumption of E. purpurea was associated with an increased risk of rash (Taylor et al. 2003).

Regarding side effects, Echinacea is often well tolerated with the most common side effect being its unpleasant taste (Hughes et al. 2004, Parnham 1996). Extended use of Echinacea for more than 2 months may lead to tachyphylaxis (Blumenthal et al. 1998). Anaphylaxis has also been reported with a single dose of this herbal agent (Ness et al. 1999). Further, Echinacea use has been associated with hepatotoxicity if taken with hepatotoxic agents including anabolic steroids, amiodarone, ketoconazole, and methotrexate (Miller 1998). Further, flavonoids from E. purpurea can affect the hepatic cytochrome P-450 and sulfotransferase systems (Eaton et al. 1996, Schubert et al. 1995). For example, one investigation found that Echinacea decreased the oral clearance of substrates of the cytochrome P-450 1A2 system but not the oral clearance of substrates of the 2C9 and 2D6 isoenzymes in vivo. The herbal also selectively modulates the activity of the cytochrome P-450 P3A isoenzyme at both hepatic and intestinal sites. The researchers, therefore, urged caution when Echinacea is combined with medications dependent upon the cytochrome P-450 3A or 1A2 systems for elimination (Gorski et al. 2004). Drug levels may become elevated with concomitant use of Echinacea. Some drugs that are metabolized by the cytochrome P-450 3A enzyme include lovastatin, clar-ithromycin, cyclosporine, diltiazem, estrogens, indinavir, triazolam, and numerous others. Taking midazolam and Echinacea together seems to increase levels of the sedative (Gorski et al. 2004). Finally, Echinacea use should exceed 4 weeks and it should not be used in patients with systemic or autoimmune disorders, patients who are pregnant, or patients who are immunocompromised (Hughes et al. 2004, Bordia 1978).

The immunostimulatory effects of Echinacea may antagonize the immunosuppressive actions of corticosteroids and cyclosporine (Chavez and Chavez 1998). Echinacea may also lead to inhibition of the hepatic microsomal enzyme system and as such its use with drugs such as phenobarbital, phenytoin, and rifampin, which are metabolized by these enzymes, should be avoided as toxicity may result.

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