Echinacea: key concepts and controversies

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There are a total of nine species of the Echinacea genus, with three varieties being used in modern western herbal practice. These are E.angustifolia, E.purpurea, and E.pallida. The genus can vary in size across the different species, from a height of around 0.5m for E.angustifolia to in excess of 1.5m for E.purpurea (Boon & Smith 2004 p91). The plant is of the asteracea family and is native to the North American midwest (2004 p91). It grows on the prairies with a preference for sandy soils (Mills 1993 p488). It is here in the American midwest that its traditional usage is first recorded. Echinacea has been a major plant used in Native American healing systems for centuries. Its application ranged from treating external wounds and pain relief to an antidote to common poisons such as snake venom, hence the pseudonym 'Snake root' (Schar 1998 p97). It is a herb that has gained a lot of attention, especiallly in recent years, as somewhat of a panacea, especially where the immune system is concerned. In modern herbal practice, Echinacea is used for upper respiratory tract infections such as colds and flu's, and infections in general. However, are all the claims surrounding it justified?

The first recorded usages of this plant is from Native American Indians. The Kiowa Indians chewed the roots of E.angustifolia for coughs and sore throats, the Cheyenne chewed the roots and infused the leaves of E.pallida for the treatment of common cold symptoms, and the Choctaw chewed and tinctured the roots of E.purpurea for the treatment of coughs (Borchers et al 2000 p343). However it seems the primary use across all communities was for infected wounds and bites (Schar 1998 p97). A later group who held Echinacea in high regard, and virtually claimed it as their own, were the Eclectics. In their prime during the early twentieth century, the Eclectics experienced a great success in treating bacterial infections, at a time when allopathic medicine could not (1998 p97). The reason for this, E.angustifolia. They also used it for the treatment of kidney and urinary tract disorders, and as a vulnerary (Thorne res inc 2001 p411). They were however quite openly critical about the therapeutic value of the other two species commonly used (1998 p97). This popularity of use experienced a sharp decline however after the arrival of antibiotics (2001 p411). In recent times, Echinacea has experienced something of a rebirth, and on a very significant scale. It is now possibly the most well known herb in the west by medics and lay-people alike.

Today Echinacea is among the most commonly used medicinal plants in the west. It has gained a considerable reputation as a remedy for the common cold, flu, and their symptoms (Turner 2002 p1001). Its use by the modern Medical Herbalist is frequently to tackle infections of the upper respiratory tract and general infections (Hoffmann 2003 p544, Bone 2003;185). As a result of this common application and long standing reputation, a great deal of pharmacological research is emerging, much of which is supporting these reported actions. Research has highlighted that Echinacea has the ability to stimulate non specific, or cell-mediated immune responses. Administration of this herb increased the number of circulating leukocytes, activated macrophages and stimulated white cell production in the bone marrow (Mishima et al 2004 p1008). It was shown to increase the production of IFN-gamma (2004 p1008), a protein produced by lymphocytes, macrophages, and fibroblasts (2004 p1008, Tortora & Grabowski 2003 p776). This protein lowers IgG and IgM responses, therefore causing a supression of antibody-mediated immunity and a promotion of cell-mediated responses (2003 p776). Could this offer a potential antiallergy application? A study testing the action of a commercially available Echinacea product that consisted of both arial parts and roots found similar results. An increased phagocytic action of Human granulocytes has been observed (Borchers et al 2000 p343). The study also revealed a stimulation of cytokine production. TNF-alpha, IL-1, and IL-10 were found in relatively high concentrations (2000 p343). This particular study was however conducted in vitro so cannot be completely relied upon as an indication as to the herb's effects in patients, because the compounds instigating these effects may not be absorbed via oral administration. Notable results have been achieved from administering the fresh juice of E.purpurea. These results included a significant stimulation of peripheral leukocytes and an increase in the production, again of IL-1, IL-6, IL-10 and TNF-alpha (Mills & Bone 2000 p356). Research such as the above mentioned, has clearly defined this herbs ability to influence the immune system. The major controversy that seems to have arisen however, is the question of what active component of the plant is doing this and how. It is therefore pertinent to explore the most widely known constituents and the studies carried out on them.

Caffeic acid derivatives

These constituents are present mainly in the roots of this genus. They are phenolic compounds that are primarily anti-inflammatory and antibacterial agents (Pengelly 1996 p62, Schar 1999 p96). The main derivatives of importance are ecinacoside, chicoric acid, and cynarin. Ecinacoside, a caffeic acid glycoside, has long been a focal point for manufacturers of standardized extracts that market their products as immune boosting supplements. However, no immunomodulatory effect from this compound has been found in any clinical trial to date (Bone 1998 p5). This obviously raises questions of efficacy of this type of product. Chicoric acid is found in E.purpurea and has been shown to have a stimulatory effect upon phagocytes (Bone 1998 p5). An inhibitory effect upon HIV infection has also been attributed to this constituent. For HIV infection to take place, HIV-integrase must covalently join the viral cDNA into a host chromosome (Rienke et al 2004 p203). Chicoric acid has been shown to inhibit this integration (2004 p203). This constituent, also found in chicory, may be found in variable amounts in fresh herb preparations. This appears to be due to enzymes naturally present in the fresh plant catalyzing the breakdown of this acid (Bone 1998 p5). Chicoric acid does however appear to be stable in dried plant preparations (1998 p5). The constituent cynarin is found only in E.angustifolia. It appears that this constituent has a hepatoprotective property to it, enabling the liver to deal with toxins more effectively (Bone 1998 p6) although the mode of action responsible for this is unclear.

Polysacharides

These appear to be the most hottly debated compounds present. Many trials have focused purely upon them. The most widely known are PSI and PSII. PSI is a 4-0-methylglucoronoarabinoxylan composed of glucuronic acid and the sugars arabinose and xylose (Bone 1998 p4). PSII - is an acidcarbinorhamnogalactan, composed of the sugars arabinose, rhamnose, and galactose (1998 p4). These substances have been widely studied as possible immunomodulating agents. There is some speculation that these polysaccharides have an antiviral property and are able to block the virus receptors on cell surfaces and prevent incorporation of the virus (Willard 1992 p85), but this is yet to be confirmed. These polysaccharides have been shown to stimulate T-lymphocyte numbers and activity in-vitro. One study performed on rats did show an increase in the production of IL-1, IL-6 and TNF-alpha from the application of these polysaccharides in-vitro (Roesler et al 1991 p27). But can this in any way related to human oral application? some of the findings that have arisen from oral polysaccharide administration may not necessarily be significant because these studies rely upon a high concentration of polysaccharides to instigate this action. It has been shown that the absorption of these polysaccharides via oral administration is around 1% (Bone 1998 p5). Therefore the kind of dosage of Echinacea given by the practicing herbalist may not be effective due to a low concentration of these substances. However, the action of these compounds may serve to support the traditional use of these plants as topical wound healing agents. It seems that in this application there is an inhibition of the enzyme hyaluronidase (Hoffmann 2003 p544, Bone 2003;185). This occurs by the formation of a polysaccharide complex with hyaluronic acid (Bove 1990 p25). A reduction of hyaluronidase lowers the rate of diffusion across cell membranes of hyaluronic acid (1990 p25). This temporary increase in hyaluronic acid causes stimulation of fibroblasts, thus stimulating the wound healing process.

Alkylamides

These are not particularly common constituents. They are found in E.angustifolia, and E.purpurea, but not in pallida and are responsible for the tingling tongue sensation attributed to the preparations of these two plants. Studies have shown that these compounds are particularly active in the role of immuno-stimulation. Trials have shown these compounds to significantly increase general phagocytic activity and increase nitric oxide production from macrophages (Goel et al 2002 p381). A stimulatory action upon TNF-alpha production has also been demonstrated (Gertsch et al 2004 p563). It is belived that the alkylamides present in E.angustifolia and E.purpurea have a role to play in the anti-inflammmatory action of this genus. This may be done by inhibiting cyclooxygenase and 5-lypoxygenase (Mills & Bone 2000 p357).

Possible further applications

The common use for this herb has always been associated with treating infections of some kind, be they internal or external. However, research has come to light that is suggesting a quite different potential application. This new application is a possible treatment for hormone-linked conditions. An in-vivo trial carried out on male rats with benign prostatic hyperplasia showed a significant decrease in the size and weight of the prostate after 8 weeks continual administration of whole Echinacea (Skaudickas et al 2003 p761). It is suggested that this is due to an androgenic effect (2003 p761). In an attempt to further explore this action, the same researchers carried out a further study on male rats with no prostate complications at all. After 8 weeks of administration of Echinacea it was found that there was a reduction in testicle size and an inhibition of spermatogenesis (Skaudickas et al 2004 p1211). This result appears to be contradictory to the previous results. Such an effect upon sexual glands would suggest an antiandrogen effect. This research does highlight some kind of interaction with the endocrine system that may give rise to a potential future application. However, research is in the very early stages at present, thus more must be carried out to clarify the interaction before any clinical decisions could be made regarding this application.

Contraindications and safety considerations

It appears that in general Echinacea is a well tolerated herb. Clinical trials in rats have shown a high tolerance (Mills & Bone 2000 p355), but some allergic responses have been observed in some Human participants (2000 p355). It is believed by some that there is a possibility that Echinacea can exacerbate any pre-existing autoimmune diseases. Increased TNF-alpha may play a role in this (Lee & Werth 2004 p723). There are potential contradindications in this herbs application in conditions such as multiple sclerosis and collagenosis, possibly due to the stimulatory action of fibroblasts (Brinker 2001 p83). There may also be problems in using Echinacea in conditions such as leukosis, due to the fact that there is non-specific white cell stimulation, which may in turn affect immune responses (2001 p83). There are also reports that there could be a possible adverse effect upon infertility in men. One study found Echinacea to have an interference with the enzymes of spermatazoa thus reducing their motility (Ondrizeck 1999 p87) and the previously discussed antiandrogen research found this effect to be true in male rats (Skaudickas et al 2004 p1211), so may support this claim.

For the practicing herbalist, it seems there are several important issues surrounding the clinical application of Echinacea. The first of these is exactly which studies should be credited. Although there are countless studies that demonstrate a stimulatory effect upon the immune system, there are just as many that demonstrate no effect whatsoever. Studies by Yale & Liu (2004), Sperber et al (2004), and Taylor et al (2003) are three examples of studies that showed no measurable effect upon upper respiratory tract infections. These three particular studies all used whole herb capsules, and each of these studies were stringently controlled randomised clinical trials. On the other side of the coin there are volumes upon volumes of traditional, empirical evidience that cite this herb as greatly effective in treating the symptoms of general infections. On the basis of this it is safe to assume that available research is inconclusive. In such instances, does the practicing herbalist work purely with their own experience?

Practitioners may also face issues of confusion regarding which species and which part of the plant to actually use and in what way to prepare them. Much of the modern research available is focused around the aerial parts of E.purpurea (Yale & Liu 2004, Sperber et al 2004, Skaudickas et al 2004), and extracts thereof (Roesler et al 1991). The Eclectics used solely E.angustifolia and used preparations made from the roots of the plant (Schar 1998 p98). When this information is compared to that of the American Indians, it becomes clear that, although they used three different species, they too favoured preparations made from the roots of the plant (1998 p97, Borchers et al 2000 p343). With regards to the preparations themselves, both the Eclectics and the American Indians used the plant fresh. This type of preparation is logical as some of the constituents that have been identified are particularly fragile. Polysaccharides for example are particularly prone to denaturing in ethanolic extractions (Bone 1998 p6). Alkylamides are at risk of oxidising if stored for long periods of time (1998 p5). In contrast, the constituent chicoric acid is more stable in a dried product (1998 p5), but how relevant is this? Contrasts such as this may lead to confusion and draw the practitioner towards using a preparation that may be ineffective. A further issue surrounding this is that of availability of fresh produce. Will this force practitioners to opt for other preparations?

Conclusion

The immune enhancing reputation of this herb is a long standing one, cited by some of the greatest herbal physicians of our time. However, its seeming resurrection in recent years has given rise to vast amounts of research being conducted in an attempt to 'prove' this effect. In keeping with the reductionist methodologies of modern scientific research, it is often the plants' individual constituents that have been studied, and in a way that would in no way represent a herbal practitioners method of administration. It comes as no suprise that such research would be contradictory to the traditional texts. Native American Indians, and the Eclectics only used preparations made from the fresh herb, and had no inclinations towards or concept of, rigorously extracting individual constituents in order to pinpoint the one 'magic bullet'. This illustrates the importance of remembering the synergistic effects of all these constituents working together as a whole biologically active entity. Much of the confusion and controversey surrounding Echinacea and many of the members of our materia medica has arisen for this very reason. In light of this, although we must remain aware of the outcomes of modern research, we would be foolish to ignore recommendations made by those that paved the way for our therapy when making our clinical decisions.

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