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 Echinacea: Fact and Fiction By Kerry Bone, BSc (hons.), Dip. Phyto Editor's note: Click here to read part two of Dr. Bone's article. The most well-known herbal support for the immune system is echinacea. But many patients and practitioners are confused as to the best way to use this herb. There are many echinacea products available, which differ according to plant species (E. angustifolia, E. purpurea, E. pallida or combinations of these), plant part (root, leaves, seeds or combinations of these), quality markers (alkylamides, polysaccharides or caffeic-acid conjugates such as cichoric acid) and dosage.Underlying this diversity of preparations was a lack of consensus over what phytochemicals are responsible for echinacea's immune activity and only a rudimentary understanding of the exact mode of action of this herb on immune function. However, recent research has provided some answers to these key questions. In particular, the alkylamides, the unique and characteristic phytochemicals found mostly in the roots of E. angustifolia and E. purpurea have been shown to be the best choice as markers of immune activity. This research validates the traditional preparations prized by 19th-century herbalists. Historical Context Before discussing the new research developments for echinacea, its use as an immune herb needs to be understood in its historical context. Information about the therapeutic value of echinacea first came from Native American tribes. Their use of echinacea root was then adopted by the Eclectics, a group of doctors who were prominent around the late 19th and early 20th centuries in the US. By 1921, echinacea (specifically the root of E. angustifolia) was by far, the most popular treatment prescribed by Eclectic physicians.1 The Eclectics used echinacea for about 50 years and accumulated extensive clinical experience in its use. The best sources of such uses are King's American Dispensatory2 and Ellingwood's American Materia Medica.3 What also is important to note is that echinacea's reputation as an immune herb came from the solid traditional data generated by the Eclectics on only one form of echinacea: a fluid extract of the dried root of E. angustifolia extracted in a high percentage of alcohol. We can call this a "traditional echinacea extract." Because it was extracted in a high percentage of alcohol, the term "lipophilic extract" (fat-loving) also is relevant. In particular, the Eclectics defined good-quality echinacea root "as imparting a persistent tingling sensation," which is a clear reference to alkylamide levels as a quality indicator.2 In Europe during the 1930s, the German herbalist Madaus used E. purpurea, as he was more successful at growing this species. His interest in homeopathy led him to use the stabilized juice of fresh E. purpurea tops. This remains the most popular form of echinacea in Germany today (and contains very low levels of alkylamides). We can call this style of product a "hydrophilic extract" (water-loving) of echinacea. Naturally, German scientists were interested in investigating how these new hydrophilic extracts of echinacea might work in the body and undertook a search for active components. Polysaccharides possessing immunological activity were isolated from the aerial parts of E. purpurea.4 Some clinicians and scientists then mistakenly applied this research to the very different lipophilic or traditional echinacea preparations and came to the conclusion that they were therapeutically inferior because of their low or absent content of polysaccharides. (The low levels of polysaccharides in traditional echinacea extracts are due to the low starting levels in the root and the fact that high levels of alcohol do not effectively extract these water-loving molecules.) However, many herbal clinicians remained unconvinced. A key aspect of modern phytotherapy is a respect for traditionally-generated knowledge and this suggested that a lipophilic extract of E. angustifolia root was the preferred form. Some felt that the concept of polysaccharides failed to explain what was unique about echinacea and expressed concerns about the low oral bioavailability of these large, polar compounds.5 So, what was clearly needed was a different understanding of echinacea, especially of the phytochemicals important for the activity of traditional echinacea products and their mode of action on the immune system. Some of the confusion about echinacea use has arisen from misinterpretation or overemphasis of the polysaccharide research. Statements such as: "Echinacea will not be immunologically active if given as an ethanolic extract," or "Echinacea is a T-cell activator" or "Echinacea is contraindicated in AIDS," have all arisen from an overly enthusiastic interpretation of the pharmacological literature pertaining to echinacea polysaccharides. It is worthwhile to first examine what the pharmacological studies on echinacea polysaccharides really say and then to consider the relevance, if any, of these to the normal use of echinacea. Dispelling the Polysaccharide Myth Two immunostimulatory polysaccharides (PSI and PSII) were isolated from the aerial parts of E. purpurea in the 1980s.4 Studies showed PSI to be a 4-O-methyl glucurono-arabinoxylan (that is, mainly composed of glucuronic acid and the sugars arabinose and xylose), while PSII was shown to be an acidic arabinorhamnogalactan (mainly composed of the sugars arabinose, rhamnose and galactose).4 However, most of the studies on echinacea polysaccharides have been on those derived from tissue cultures of E. purpurea, which yielded two fucogalactoxyloglucans and an arabinogalactan (AG).4 Tissue cultures are artificially cultured plant cells. As expected, the structure of the tissue culture polysaccharides differed from those of the aerial parts of the naturally grown plant, since cells in culture possess only primary cell wall components.4 Echinacea polysaccharides (EPS; a protein-free, highly enriched polysaccharide mixture from the aerial parts of E. purpurea) seem to preferentially stimulate the mononuclear immune system in vitro.4 EPS stimulated both peritoneal and bone marrow macrophages to behave cytotoxically in vitro.4 In a second experiment, it was shown that EPS stimulated bone marrow macrophages to release interleukin 1 (IL-1), although it was much less potent than endotoxin in this respect.4 Subsequent research was mainly on either an acid arabinogalactan (AG) or an industrially prepared polysaccharide mixture (EPAG), both isolated from tissue cultures of E. purpurea.4 AG induced a dose-dependent release of tumor necrosis factor α (TNF α) from peritoneal macrophages in vitro.4 When bone marrow macrophages were used in vitro, a dose-dependent release of interferon β2 (IL-6) also was found.4 There also is indirect evidence that EPAG stimulates TNF α from peritoneal macrophages in vitro.4 The effect of echinacea arabinogalactan from tissue cultures (AG or EPAG) is strikingly selective for macrophages in vitro.4 EPAG given by intravenous injection to mice at the very high dose (relative to levels in echinacea) of 10 mg/kg caused a protective effect against Candida albicans infection.6 Similar tests have been performed with positive results. It is worthwhile at this point to examine some of the erroneous conclusions about the use of echinacea which have been drawn from this research on polysaccharides. In vitro effects observed on isolated cells are not necessarily translatable to whole organisms. In other words, there are biological mechanisms in the whole organism that can modify the effects observed in in vitro models. In particular, gastrointestinal breakdown, poor absorption and poor tissue mobility of polysaccharides would suggest there are many significant unknowns in the translation of in vitro findings to effects in a living organism after oral dosage. Polysaccharides are very large molecules that are destroyed in the colon by bacterial activity.7 Research on acemannan from aloe vera juice shows that polysaccharide absorption through the gut is only about 1 percent.8 In order to achieve immunologically active doses, a daily dose of about 600 mL of aloe vera juice, which is rich in polysaccharides, must be consumed. This implies that the relatively low quantity of polysaccharides in E. purpurea tops (let alone root preparations) will not be absorbed in levels sufficient to achieve the concentrations used in the in vitro studies. Perhaps the polysaccharides may act directly on gut tissue (e.g., Peyer's patches) but even then, it is doubtful they would be present in pharmacologically significant quantities in most echinacea preparations. Moreover, such effects would not explain the activity of echinacea on bone marrow (see explanation later in this paper). A recent clinical trial (in fact the only one published to date on echinacea polysaccharides) failed to show marked effects on immune function. In an open, prospective study with matched historical controls, a polysaccharide fraction isolated from E. purpurea cell cultures was tested to see if it could counter the undesired immune side effects of cancer chemotherapy.9 Fifteen patients with advanced gastric cancer undergoing palliative chemotherapy with a range of cytotoxic drugs also received daily intravenous injections of 2 mg of a polysaccharide fraction from echinacea. While the polysaccharide treatment did appear to increase white cell counts, there were no clinically relevant effects on phagocytic activity or lymphocyte subpopulations. The above clinical research reveals the fundamental flaw behind attempts to explain the activity of echinacea in terms of polysaccharides. In the trial, the polysaccharides were administered by injection because their oral bioavailability is uncertain. If the trial scientists had believed that the polysaccharides were orally active, then they would have administered them this way. Alkylamides Are Bioavailable It can be concluded from both traditional use and clinical studies that echinacea acts on the immune system at various sites in the body. Hence, for echinacea to exert this influence, it seems reasonable to suggest that the active phytochemicals must be absorbed in significant quantities in the bloodstream. Accordingly, both test tube (in vitro) and clinical (pharmacokinetic) research was initiated to understand which of the key phytochemicals in a lipophilic extract of echinacea root were absorbed. In contrast to the polysaccharides, alkylamides were found to be highly bioavailable. A particular strain of human colon cells (Caco-2) can be grown in a test tube to form a tight layer of single cells (a monolayer). This can serve as a model of absorption by the human digestive tract. The test components are placed on one side of the monolayer and after a period of time, anything that has been transported across to the other side of the monolayer is sampled and measured. Research using an echinacea extract made from the roots of E. angustifolia and E. purpurea found that all the alkylamides were transported across the Caco-2 monolayer, but the caffeic-acid derivates were not transported.10,11 Hence, results from this model indicate that only the alkylamides in traditional echinacea extracts are likely to be absorbed (and hence bioavailable to the immune system). These results from the Caco-2 model were then confirmed in a human pharmacokinetic study. Volunteers took 4 tablets of a commercial echinacea root preparation with a meal and the levels of any detectable echinacea phytochemicals were measured in their blood. Only alkylamides could be detected in the blood after taking this preparation. There were no caffeic acid conjugates found and no degradation products of either these or the alkylamides.12 References
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All Rights Reserved, Naturopathy Digest, 2011.
Date Last Modified - Friday, 17-Oct-2008 12:11:13 PDT
About the Author: Kerry Bone was an experienced research and industrial chemist before studying herbal medicine full-time in the UK, where he graduated from the College of Phytotherapy and joined the National Institute of Medical Herbalists. He is a practicing herbalist; co-founder and head of research and development at MediHerb; and principal of the Australian College of Phytotherapy. Kerry also is the author of several books, including Principles and Practice of Phytotherapy and The Essential Guide to Herbal Safety.
