Botanical Name(s):

Family: Asteraceae      Genus: Echinacea

Echinacea purpurea ; Echinacea angustifolia; Echinacea pallida ;
Echinacea simulata; Echinacea paradoxa; Echinacea tennesseensis; Echinacea laevigata; Echinacea sanguinea; Echinacea atrobubens; Echinacea gloriosa

Common name(s): Echinacea; Purple Coneflower; Kansas Snakeroot; Black Sampson

Echinacea has had a long history of being utilized as a healing herb by Native American people. ¹ In the 1800’s it became popular with the medical community in the United States and was a widely prescribed natural remedy for infections and inflammation. Its usage was recommended and studied during this time by the renowned Dr. Uri Lloyd, Dr. John King and Dr. H.C.L. Meyer. ^{2 /3} The root and rhizome were officially recognized by the National Formulary (NF) from 1916 to 1950.

Though its popularity in America waned with the onset on antibiotics, its usage continued in Germany where it was often used to treat viral infections and inflammatory conditions. The German Commission E recognized E. Purpurea herba (above ground parts) as an approved herb in 1989. On August 29th, 1992, E. Pallida radix (root) also attained this status. However, E. Angustifolia (herba and radix), E. Purpurea radix, and E. Pallida herba are still listed as unapproved as of 1998. This is most probably due to a lack of current clinical research. ⁴ There are also approximately six to seven other varieties of Echinacea however no mention is made of these other Echinacea types in the Commission E monographs.

Though the Commission E has only approved two varieties and then in limited scope, there is wide spread usage of Echinacea angustifolia, E. pallida and E. purpurea. Echinacea products are often sold as a combination of these three. There has been some speculation that E. angustifolia may have stronger medicinal value than the others although to date there is no clinical data that substantiates this claim. Currently, the United States Pharmacopoeia/ National Formulary is reviewing Echinacea for inclusion in its Botanical monograph series. (Note: the USP was established in 1820 to create standards for the use and quality of pharmaceuticals and combined with the National Formulary in 1980). ^5/6

Echinacea is a hardy perennial plant that grows 1-2 feet tall and has a spiny appearance from which it derived its name (echinos being Greek for sea urchin or hedgehog). It is a member of the daisy family and its flowers can resemble Black-eyed Susans with rich purple petals radiating from the center. The rhizome has circular pith. It has a faint aromatic smell. It grows throughout the United States from the mid-west to the prairie regions of Pennsylvania. Each of the varieties has a slightly different appearance. E. Purpurea demonstrates the classic purple flower and so too does E. Angustifolia though with narrower leaves and smaller flowers. However, E. Paradoxa has yellow flowers, E. Atrorubens and E. Sanguinea have dark red flowers, and E. Pallida and E. Simullata have pale purple flowers.

Due to an over harvesting of its wild population, some states restrict the harvest of this herb and are considering it for endangered species status. Since Echinacea purpurea is the easiest species to grow commercially, it may become the most utilized in the United States, as is the case in Europe. ⁷ It is a very popular herb in the United States, generating more than $300 million in sales annually. ⁸

A concern in purchasing Echinacea is the practice of substitution. It should be noted that Parthenium integrifolium or by it’s common name, Prairie Dock, is sometimes sold as Echinacea and has been since as early as 1909. Labels should be checked for clear identification of the plant genus utilized. In the 1980''s, it was discovered that some German researchers had been (unknowingly) receiving Prairie Dock under the name of Echinacea. This has thrown doubt into the reliability of the research done on the herb during that time frame. ^9/2 Unknown mixing or substitution of species has also been a problem in past research. Many studies conducted on what was thought to be E. angustifolia during this same time frame were later proven to have been E. Pallida. ⁴

Herbal remedies are under no enforced regulations and selling a standardized product is voluntary on the manufacturers part. Since it is thought that the quantity and composition of the bioconstituents present effect the reliability and efficacy of a product, this is something to be aware of. This practice of substitution still exists, so read the labels carefully! Still even if the correct genus is listed, adulterations, absence of specific constituents, labeling that lacks information should all be cause for care when purchasing.

With the awareness of substitution and the work that has been done on the chemistry of certain species, research today is able to focus on the specific varieties and/or constituents. Generally, Echinacea is thought to create activity in the immune system by stimulating T-cell production, phagocytosis, lymphocytic activity, cellular respiration, activity against tumor cells (thought it’s application is debatable) and inhibiting hyalurinadase enzyme secretion. Its natural antibiotic (echinacoside) is said to be comparable to penicillin in its broad-spectrum affects however there are questions as to whether there is enough present in the herb to have a significant effect. It may inhibit a broad range of viruses, protozoa, bacteria, and fungi. Echinacea contains echinacein which seems to counteract against the enzyme hyaluronidase that microbes produce to penetrate tissues and cause infection. It is has been indicated in studies that it is effective in decreasing the frequency and severity of colds and the flu. (See Published Studies)

Echinacea is considered a safe herb. Incidents of adverse reactions are rare and there is no known toxicity. However, it is not recommended in progressive systemic and auto-immune disorders s.c. as AIDS, tuberculosis, multiple sclerosis, leicosis, connective tissue disorders, collagenosis and related diseases s.c. as lupus. ^4/10 (See Published Studies and also Contraindications). It should be noted that in cases of AIDS and AIDS opportunistic infections there is still considerable debate occurring over echinacea usage.

Biochemical Constituents:

Echinacea Simulata and E. Paradoxa Roots:

In a 1991 study "The constituents of the roots of Echinacea simulata and E. paradoxa were examined by HPLC (high pressure liquid chromatography). The major lipophilic and hydrophilic compounds could be identified. E. Paradoxa contained several ketoalkenynes and proved to have almost identical constituents as E. pallida. E. Simulata contained alkamides as found in E. angustifolia and in addition ketoalkenynes as in E. pallida. Echinacoside was found in both species." ¹¹

Echinacea Angustifolia, Echinacea Purpurea, and Echinacea Pallida:

Some biochemical constituents all three have in common are echinacoside, polysaccharides, glycoproteins and a caffeic acid derivatives (cichoric acid), triglycoside of caffeic acid derivative echinacein. ^12/14

  If listed as Echinacea spp. Compositae: the biochemical constituents have been recorded as follows: essential oil containing the oncolytic hydrocarbon (z)-1,8- pentadecadiene, polysaccharide 1 (a heteroxylan) containing arabinose, xylose, glactose, glucose, and 4-0-methylgluronic acid; polysaccharide 2 (an arabinorhamnogalactic) containing rhamnose, arabinose, galactose, and glucuronic acid; echinacen (an isoabutylkyamide comprising 0.01% of the dried root of E. angustifolia and 0.001% of the dried root of e. pallida); echinolone (appolyacetylene compound from E. angustifolia); echinacoside ( a glycoside found in E. angustifolia, at concentrations of 1% of root preparations); echinacin B; an unsaturated aliphatic sesquiterpene*; betain; insulin; inuloid; fructose; sucrose; higher fatty acids; 6.9% protein in air dried roots of E, angustifolia, 5.3% in E. purpurea; tannin; vitamin C; enzymes; an unidentified glucoside; resin; acids and thirteen polyacetylene compounds ¹³ (there is a theory that these are formed during storage, since it is said that they are found in dried but not fresh roots of E. pallida ).

*Note: Originally some commercial samples of E. purpurea were identified as containing Sesquiterpene esters however data has since shown that this was due to the presence of an adulterant, Parthenium integrifolium L. It appears that this adulteration may be widespread in commercial samples. ¹³

Medicinal parts: Roots, Leaves, Seed and Rhizome. Fresh or sometimes dried.

It should be noted that the best p.r. of the plant to use is under debate. An alcoholic extract of the root of E. Pallida and the expressed juice of the aboveground plant of E. Purpurea at the time of flowering are the parts approved for use by the German Commission E. ⁴ These have had numerous in vitro and in vivo studies conducted on their pharmacological viability. ¹⁴

Preparation, dosage and appropriate method of intake are still in debate however there are some general guidelines.

One article reads "No well-controlled studies have evaluated the appropriate formulation or the dosages that are available on the market. Herbal publications typically state that the maximum adult daily dosage is 6 to 9 ml of expressed, fresh juice, 1.5 to 7.5 ml of tincture (preferred because not all the constituents are water soluble) or 2 to 5 g of dried root." ³²

"Daily intake should be restricted to what is deemed necessary. However, for the maintenance of a healthy immune system, echinacea is most wisely used periodically--a few weeks on, and a few weeks off, throughout the year." ⁶⁰

TABLE 1 - Echinacea spp.; Compositae - Usual Dosage for Solid (Dry powdered) extract

TABLE 2 - Echinacea spp.; Compositae - Usual Dosage for Solid (Freeze dried plant)

TABLE 3 - Echinacea Pallida Herba and Radix - Usual Dosage for Tincture 1: 5 ratio

TABLE 4 - Echinacea Purpurea Herba - Usual Dosage for Pressed Juice

TABLE 5 - Echinacea Purpurea Radix - Usual Dosage for Tincture

Note: Preparations should be protected from light sources.

TABLE 6 - Echinacea Angustifolia Herba and Radix - Usual Dosage for Tea

Note: Preparations should be protected from light sources.

It is usually orally taken in a solid or liquid form.

REFERENCES

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Additional References:

• Snow, J.: Echinacea (Moench) Spp. Asteracae, The Protocol Journal of Botanical Medicine. 20:18-23 (1997).
• HerbalGram. Echinacea: A Literature Review. Austin, Tex.: Herbal News, 1994;30(Suppl):33-48.
• Wagner H, Jurcic K: Immunologic Studies of Plant Combination Preparations. In-vitro and In-vivo studies on the Stimulation of Phagocytosis (Immunologische Untersuchungen von pflanzlichen Kombinationspraparaten. In-vitro-und In-vivo-Studien zur Stimulierung der Phagozytosefahigkeit), Arzneimittelforschung (1991 Oct) 41(10):1072-6ISSN: 0004-4172 (Published in German)
• Schutte A: Is Research in Veterinary Homeopathy Justified? Thoughts Concerning Principles and Synopsis of 5 Years of Research on the Subject, "Use of Homeopathy in Domestic Animals, at the Branch of the Free University of Berlin in Schwarzenbek (Ist Forschung in der Veterinarhomoopathie gerechtfertigt? Grundsatzgedanken undeine Zusammenschau uber 5 Jahre Forschung zum Thema "Anwendung der Homoopathiebei Nutztieren" an der Aussenstelle der Freien Universitat Berlin in Schwarzenbek), Berl Munch Tierarztl Wochenschr (1994 Jul) 107(7):229-36ISSN: 0005-9366 (Published in German)
• Bukovsky M, Kostalova D, Magnusova R, Vaverkova S: Testing for Immunomodulating Effects of Ethanol-water Extracts of the Above-ground Parts of the Plants Echinaceae (Moench) and Rudbeckia L. (Testovanie imunomodulacnych ucinkov etanolovo-vodnych extraktov z nadzemnychcasti rastlin rodu Echinacea Moench a Rudbeckia L.), Cesk Farm (1993 Oct) 42(5):228-31ISSN: 0009-0530 (Published in Slovak)
• Bukovsky M, Vaverkova S, Kostalova D, Magnusova R, Immunomodulating Activity of Ethanol-Water Extracts of the Roots of Echinacea gloriosa L., Echinacea angustifolia DC. and Rudbeckia speciosa Wenderoth Tested on the Immune System in C57BL6 Inbred Mice, (Imunomodulacna aktivita etanolovo-vodnych extraktov z korennov Echinaceagloriosa L., Echinacea angustifolia DC. a Rudbeckia speciosa Wenderoth testovanana imunitnom systeme inbrednych mysi C57BL6), Cesk Farm, 1993, Aug, 42(4):184-7 ISSN: 0009-0530 (Published in Slovak)
• Domio M: Sparking the Decision of Choice between HIV Treatment Regimens: Western vs.Naturo- and Homeopathic Medicine, Int Conf AIDS, 1996, Ju,l 7-12, 11(2):424 (abstract no. Th.D.5121)
• Egert D, Beuscher N: Studies on Antigen Specifity of Immunoreactive Arabinogalactan Proteins extracted from Baptisia tinctoria and Echinacea purpurea, Planta Med, 1992, Apr, 58(2):163-5ISSN: 0032-0943
• Muller-Jakic B, Breu W, Probstle A, Redl K, Greger H, Bauer R: In vitro Inhibition of Cyclooxygenase and 5-Lipoxygenase by Alkamides from Echinacea and Achillea Species, Planta Med, 1994, Feb, 60(1):37-40ISSN: 0032-0943
• Bukovsky M, Vaverkova S, Kost''alova D: Immunomodulating Activity of Echinacea Gloriosa L., Echinacea Angustifolia DC.and Rudbeckia Speciosa Wenderoth Ethanol-water Extracts: Pol J Pharmacol, 1995, Mar-Apr, 47(2):175-7ISSN: 1230-6002
• Dorsch W: Clinical Application of Extracts of Echinacea Purpurea or Echinacea Pallida. Critical Evaluation of Controlled Clinical Studies (Klinische Anwendung von Extrakten aus Echinacea purpurea oder Echinacea pallida.Kritische Wertung kontrollierter klinischer Studien)., Z Arztl Fortbild (Jena), 1996, Apr, 90(2):117-22ISSN: 0044-2178 (Published in German)
• Schranner I, Wurdinger M, Klumpp N, Losch U, Okpanyi SN: Modification of Avian Humoral Immunoreactions by Influex and Echinacea Angustifolia Extract, (Beeinflussung der aviaren humoralen Immunreaktionen durch Influex und Echinacea Angustifolia Extrakt)., Zentralbl Veterinarmed [B], 1989, Jul, 36(5):353-64ISSN: 0931-1793 (Published in German)
• Schulthess BH, Giger E, Baumann TW: Echinacea: Anatomy, Phytochemical Pattern, and Germination of the Achene, Planta Med, 1991 Aug, 57(4):384-8ISSN: 0032-0943
• Wichtl, M (ed), Herbal Drugs and Phytopharmaceuticals, CRC Press, 1994
• Francis Brinker, N.D., Herb Contraindication and Drug Interactions, Eclectic Institute.1997 ISBN 0-9659135-0-3
• Edited by Timothy R. Tomlinson and Olayiwola Akerele: Medicinal Plants, Their Role in Health and Biodiversity, Robert S. McCaleb :The Medicinal Plant Marketplace, Akhtar Husain: Exploitation of Medicinal Plants, University of Pennsylvania Press, 1998, ISBN 0-8122-3431-6
• Reader Digest: The Family Guide to Natural Medicine, 1993, the Reader’s Digest Association, Inc., ISBN 0-89577-433-X.
• R.C. Wren, F.L.S.: Potter’s New Cyclopedia of botanical drugs and preparations, Potter and Clark, 1907, ISBN 0 85032 009 7
• Michael Castleman: The Healing Herbs , Bantam Books, 1991,ISBN 0-553-56988-0
• Duke, James A.: Handbook of Biologically Active Phytochemicals and Their Activities, Boca Raton, FL., CRC Press, 1992
• Michael A Weiner, Ph.D & Janet A. Weiner: Herbs that Heal, 1994, Quantum Books, ISBN 0-912845-11-
• Time Life: The Drug and Natural Medicine Advisor,, 1997, Time-Life Books, ISBN 0-7835-4938-5/ 0-7835-5300-5
• Michael Murray, N.D. and Joseph Pizzorno, N.D: Encyclopedia of Natural Medicine, 1998, Prima Publishing, ISBN 0-7615-1157-1
• Michael Tierra, C.A., N.D.: The way of Herbs, Pocket Books, 1990, ISBN, 0-671-72403-7
• Steven Foster: Echinacea: Natures Immune Enhancer, Healing Arts Press, 1991
• Kindscher, K Medicinal Wild Plants of the Prairie Lawrence: University Press of Kansas, 1992. p. 86.
• Snow, J. "Echinacea (Moench) Spp. Asteracae." The Protocol Journal of Botanical Medicine. 20:18-23 (1997).
• Murray, M. "Echinacea: Pharmacology and Clinical Applications." The American Journal of Natural Medicine. 2(l):18-24 (1995).
• Schulthess BH, Giger E, Baumann TW: Echinacea: Anatomy, Phytochemical Pattern, and Germination of the Achene., Planta Med, 1991, Aug, 57(4):384-8ISSN: 0032-0943
• Paranich AV, Pocherniaeva VF, Dubinskaia GM, Mishchenko VP, Mironova NG, GugaloVP, Nazarets VV : Effect of Supposed Radio Protectors on Oxidation-Reduction of Vitamin E in the Tissues of Irradiated Rats, (Izuchenie vliianiia predpolagaemykh radioprotektorov na sostoianie redoks-sistemy vitamina E v tkaniakh obluchennykh krys)., Radiats Biol Radioecol, , Sep-Oct, 33(5):653-7ISSN: 0869-8192
• C Hobbs: Echinacea Pharmacy in History, C. Hobbs 11/7/91 7
• Voaden D, Jacobson M: Tumor Inhibitors. 3. Identification and Synthesis of an Oncolytic Hydrocar Bon from American Coneflower Roots., J Med Chem 15:619-23, 1972
• Wacker A, Hilbig W: Virus-Inhibition by Echinacea Purpurea, Planta Med 1978 Feb;33(1):89-102 (Published in German)
• Wagner V, Proksch A, Riess-Maurer, et al: Immunostimulating Polysaccharides (Heteroglycanes) of Higher Plants - Preliminary Communication, Arzneim Forsch 34:659-660, 1984
• Mose J: Effect of Echinacin on Phagocytosis and Natural Killer Cells., Med Welt 34: 1463-7, 1983
• Donald J. Brown, N.D: Phytotherapy Review and Commentary: Med J Aust ,1998. Feb 16;168(4):170-1 - Letter for Doctors and Patients, Townsend Letters 1998

As with all Herbs and Drugs, the potential for interaction by a variety of mechanisms (eg, pharmacodynamic, pharmacokinetic drug inhibition or enhancement, etc) is a possibility.

•  According to a recent study on drug and herb interactions. If used beyond 8 weeks, Echinacea could cause hepatotoxicity and therefore should not be used with other known hepatoxic drugs, s.c. as anabolic steroids, amiodarone, methotrexate, and ketoconazole. ⁵⁸

No information provided

• Do no use in cases of HIV. ^4/10
• Do not use in cases of immune system dysfunction, autoimmune conditions (including systemic lupus) and progressive systemic conditions s.c. as multiple sclerosis, tuberculosis, leukosis, collagen disorders, and diabetes mellitus(injectable form of Echinacea). ^4/10
• Herb substitutions and adulterations have been reported in products sold as Echinacea. Read labels carefully!
• Echinacea should not be taken over a long period of time. Two to three weeks usage is considered an advisable time frame for usage (3 consecutive weeks-parenteral dosage or 8 consecutive weeks -internal and external use). Constant usage of Echinacea could keep the b.d. from regaining its natural immune capabilities. ^10/60
• If used beyond 8 weeks, Echinacea could cause hepatotoxicity and therefore should not be used with other known hepatoxic drugs, s.c. as anabolic steroids, amiodarone, methotrexate, and ketoconazole. ⁵⁸
• When utilizing with other herbs the dosage may need to be lowered. ¹⁰
• Should not be given to children younger than 2 years old without a physician’s approval.
• Minimal dosages should be given to older adults and children over the age of two when beginning treatments.

USAGE IN PREGNANCY

Do not use if pregnant - Safety for use in pregnancy has not been established. Some contraindications are thought to exist.

General

The possibility of an allergic reaction to the herb should be kept in mind during therapy.

•  If discomfort or illness occurs stop using the herb and consult you physician.

Laboratory Tests

You should always notify your physician when undertaking any herbal therapy for a prolonged period. It is always recommended that periodic assessments occur during any therapy, some of which may include laboratory testing.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Animal studies to date have shown no Carcinogenesis or Mutagenesis. ²⁷ Further studies would need to be conducted to verify these findings. Studies in animals have not been performed with this herb with regard to Fertility Impairment.

Pregnancy

Do not use if pregnant - Safety for use in pregnancy has not been established. Some contraindications are thought to exist.

Labor and Delivery

Studies have not been conducted on the effect of this herb on Labor and Delivery , therefore Extreme Caution should be taken and a physician consulted before usage.

Nursing Mothers

Studies in animals have not been performed with this herb. As many ingested substances are excreted in human milk, caution should be exercised and a physician consulted before using the herb while nursing.

Pediatric

Studies have not been conducted on the effect of this herb on children therefore Extreme Caution should be taken and a physician consulted before usage with children. Children under the age of 2 years should not take this herb. Children over the age of two should always start at the minimum dosages.

No cases of overdosages in humans has been reported.

ANIMAL TOXICOLOGY

"Single oral or intravenous doses of the expressed juice of Echinacea purpurea(EP) proved virtually non-toxic to rats and mice. After 4 weeks of oral administration in doses amounting to many times the human therapeutic dose laboratory tests and necropsy findings gave no evidence of any toxic effects in rats. Tests for mutagenicity carried out in microorganisms and mammalian cells in vitro and in mice all gave negative results. In an in vitro carcinogenicity study EP did not produce malignant transformation in hamster embryo." ²⁷

• Usage of Echinacea for treatment of HIV is not recommended at this time. ^4/10

• Echinacea should not be used in cases of immune system dysfunction, autoimmune conditions (including systemic lupus) and progressive systemic conditions s.c. as multiple sclerosis, tuberculosis, leukosis, collagen disorders, and diabetes mellitus(injectable form of Echinacea). ^4/10
• Allergies to the composite family.

• "Patients with atopy should be cautioned about the risk of developing life-threatening reactions to complementary medicines, including echinacea." ⁵⁷
• If used beyond 8 weeks, Echinacea could cause hepatotoxicity and therefore should not be used with other known hepatoxic drugs, s.c. as anabolic steroids, amiodarone, methotrexate, and ketoconazole. ⁵⁸

Clinical Pharmacology/Pharmacodynamics:

General (See Studies listed in this section below):

Echinacea is thought to create activity in the immune system by stimulating T-cell production, phagocytosis, lymphocytic activity, cellular respiration, activity against tumor cells (though it’s application is debatable) and inhibiting hyalurinadase enzyme secretion.

In inhibiting hyalurinadase, one of the constituents that is thought to effect this activity is the polysaccharide, Echinacin B. .In one study, Caffeoyl conjugates, chicoric and caftaric acids demonstrated the greatest anti-hyaluronidase activity. The enzyme hyaluronidase is produced by some pathogens to penetrate tissues and cause infection. Anti-hyaluronidase action is involved in the regeneration of connective tissue destroyed through infection and the elimination of the pathogenic organism responsible.

Macrophages are said to initiate the destruction of pathogens and cancer cells. Pollysaccharides purified from Echinacea have been noted in some studies to activate macrophages independent of T-cells.

The anti-tumor activity often attributed to echinacea but as yet unproven, has been listed as attributable to the both Echinacin and an oncolytic lipid-soluble hydrocarbon in Echinacea’s essential oil.

Echinacea is said to have the ability to increase the level of phagocytosis by raising levels of white blood cells s.c. as the neutrophils, monocytes, eosinophils, and B-lymphocytes. It also has been reported have an effect on properidin levels, indication of an activation of the complement system.

Antibiotic qualities attributed to the echinacosides glycosides are thought to be immuno – stimulating and perhaps anti-viral. It should be noted that there is still debate occurring regarding the efficacy of the echinacosides (see Microbiology).

Published Studies:

Stimulate Phagocytosis and Cytokine Secretion/ Immunological Activity:

"Echinacea exhibits the ability to stimulate neutrophil phagocytosis and cytokine secretion by macrophages.Transient lymphopenia and changes in the CD4/CD8 ratio are considered the result of redistribution of lymphocytes to areas of infection in response to echinacea." ( Echinacea purpurea) ¹⁵

Acidic arabinogalactan was effective in activating macrophages to cytotoxicity against tumor cells and micro-organisms (Leishmania enriettii). It also induced macrophages to produce tumor necrosis factor (TNF-alpha), interleukin-1 (IL-1),and interferon-beta 2. Arabinogalactan did not activate B cells and did not induce T cells to produce interleukin-2, interferon-beta 2, or interferon-gamma, but it did induce a slight increase in T-cell proliferation. "When injected ip, this agent stimulated macrophages, a finding that may have therapeutic implications in the defense against tumors and infectious diseases. ( Echinacea purpurea)" ¹⁶

Echinacea purpura polysaccharides were tested for their ability to activate human phagocytes in vitro and in vivo. They enhanced the spontaneous motility of PMN under soft agar and increased the ability of these cells to kill staphylococci. Given IV to test subjects immediately induced a fall in the number of PMNs in the peripheral blood, indicating activation of adherence to endothelial cells. "This fall was followed by a leukocytosis due to an increase in the number of PMNs and a lesser increase of monocytes. The appearance of stab cells and some juvenile forms and even myelocytes indicated the migration of cells from the bone marrow into the peripheral blood." It was observed that these polysaccharides could induce acute phase reactions and activation of phagocytes in humans ¹⁷

"Also noted in studies has been, the stimulation of macrophages (important in the destruction of pathogens and cancer cells). Oncolytic lipid-soluble hydrocarbon (from the essential oil) has been isolated within Echinacea. This constituent is thought to play an anti-tumor role." ¹⁸

In mice, ethanolic extracts of Echinacea purpurea, E. pallida and E. angustifolia roots were examined for immunological activity in the carbon clearance test and in the granulocyte test. All extracts administered orally were found to enhance phagocytosis significantly. "These results correlate with the stimulation of phagocytosis in the in vitro granulocyte test. The lipophilic fractions of the extracts appeared to be more active than the polar fractions. All extracts were analyzed by HPLC in order to correlate the chemical constituents with the immunological activities." ¹⁹

"In vitro, echinacea displays direct bacteriostatic and antiviral activity and stimulates the production of cytokines (interferon, tumor necrosis factor, interleukin 1, and interleukin . ) Based on its stimulation of cytokine production, echinacea is being investigated as a possible antineoplastic agent in preliminary human trials." ( Echinacea purpurea extracts) ²⁰

" Two preparations of Echinacea purpurea and a preparation of Eleuthero coccussenticosus increased the in vitro phagocytosis of Candida albicans by granulocytes and monocytes from healthy donors by 30-45%." ²¹

 Influex, a combination product, containing extracts of Echinacea, Aconitum, Apis and Lachesis stimulated adherence, chemotaxis, and phagocytosis, but inhibited chemiluminescence (InVitro - porcine). Results suggest an effect of the product in the generation of reactive oxygen species. ²²

"Laboratory Study: Human white blood cells, stimulated by echinacea extract increased phagocytosis (consumption) of yeast cells by 20-40% compared to controls." Cichoric acid, among other constituents, has been shown to act as an immunostimulant by causing stimulation of phagocytosis,. ²³

Echinacea purpurea extract was studied for its capacity to stimulate cellular immune function in normal individuals and patients with either chronic fatigue syndrome or AIDS. It was concluded that the extract enhanced cellular immune formation of peripheral blood mononuclear cells (PBMC) in all the subjects. ²⁴

Echinacea purpurea, E. pallida and E. angustifolia roots (ethanolic extracts) were examined for immunological activity in the carbon clearance test and granulocyte test in mice. All extracts, administered orally, were found to enhance phagocytosis significantly. "The lipophilic fractions of the extracts appeared to be more active than the polar fractions." ²⁵

"Fast atom bombardment (FAB-MS) and fast atom bombardment tandem mass spectrometry (FAB-MS/MS) techniques (negative ions) have been successfully applied for identification of the constituents responsible for the antihyaluronidase activity of Echinacea angustifolia roots, whose extracts are widely employed for the adjuvant therapy of chronic inflammatory diseases." Crude extracts were tested for antihyaluronidase activity, and those with the greatest inhibitory action. "Four main caffeoyl conjugates were detected and identified by tandem mass spectrometry (daughter and parent ion mode): 2,3-O-dicaffeoyltartaric acid (chicoric acid) and 5-O-dicaffeoylquinic acid (cynarine) and 2-O-caffeoyltartaric acid (caffaric acid) in the ethylacetate fraction." Chicoric and caftaric acids had the greatest antihyaluronidase activity. ²⁶

Microbiology:

 Some of Echinacea’s constituents are thought to have antibiotic characteristics and the ability to boost resistance to viruses and bacteria. However there is debate as to its efficacy. The contrast of thought can be seen in the following statement and studies.

"Echinacoside is thought to have antibiotic qualities and echinacein, the quality to block the mechanisms that allow viruses and bacteria to invade the body. Although some companies standardize their echinacea extracts to the caffeic acid derivative echinacoside, there is no evidence that echinacoside provides any significant antibacterial or immunological activity." ²⁸

 "In vitro, echinacea displays direct bacteriostatic and antiviral activity and stimulates the production of cytokines (interferon, tumor necrosis factor, interleukin 1, and interleukin . ) Based on its stimulation of cytokine production, echinacea is being investigated as a possible antineoplastic agent in preliminary human trials." ²⁰

"The antimicrobial activity of mercurius cyanatus complex (Oligoplex) and its components Mercurius cyanatus D5, Echinacea angustifolia D1, Ailanthus glandulosa D3, Ammonium bromatum D3, Baptisia tinctoria D3, Euspongiaofficinalis D2, alcohol 5% (dilution: D1 = 1: 10, D2 = 1 : 100 etc.) was tested in vitro by serial dilution tests against 105 clinical isolates (gram positive/negative, aerobes and anaerobes with relevance for pharyngitis)" Results were comparable to vancomycin at concentrations of 0.063-2 mg/l for S. pyogenes, S. agalactiae, S. pneumoniae, S. aureus and E. faecalis but not for H. influenza or Bacteroides sp. ²⁹

"Two preparations of Echinacea purpurea and a preparation of Eleutherococcussenticosus increased the in vitro phagocytosis of Candida albicans by granulocytes and monocytes from healthy donors by 30-45%." There was no effect in either direction on intracellular killing of bacteria or yeasts. None of the preparations induced in vitro transformation of lymphocytes. ²¹

Echinacea purpurea purified polysaccharide cell cultures were investigated for their ability to enhance phagocytes'' activities regarding nonspecific immunity in vitro and in vivo. "Macrophages (M phi) from different organ origin could be activated to produce IL-1, TNF alpha and IL-6, to produce elevated amounts of reactive oxygen intermediates and to inhibit growth of Candida albicans in vitro." In vivo the proliferation of phagocytes in spleen and bone marrow were induced as was the migration of granulocytes to the peripheral blood. Protection of mice against the consequences of lethal infections with one predominantly M phi dependent and one predominantly granulocyte dependent pathogen, Listeria monocytogenes and C. albicans, respectively was attributed to these polysaccharides. However, sheep red blood cells showed no antibody production after exposure to the polysaccharides. ³⁰

Polysaccharides isolated from large scale plant cell cultures of Echinacea purpurea (EP), have been shown to activate human and murine phagocytes. The influence of EP on the nonspecific immunity in immuno-deficient mice was studied. EP was effective in activating peritoneal macrophages following exposure to cyclophosphamide or cyclosporin A. EP treatment of immuno-suppressed mice restored their resistance against lethal infections with Listeria monocytogenes and Candida albicans. ³¹

 Researchers at Bastyr University, a naturopathic institution in Bothwell, Washington, are studying the effect of echinacea on the frequency and severity of respiratory tract infections." ³²

General:

 "Although 26 published controlled trials have evaluated Echinacea’s therapeutic effects, none is of sufficient methodologic quality to be conclusive. For example, in addition to sharing the flaws of the best studies discussed later, most other controlled trials use formulations of echinacea combined with other herbs. Treatment assignment is neither random nor blind in most studies." ³³

Anti-inflammatory activity:

Echinacea angustifolia roots polysaccharidic fraction (EPF) were studied for anti-inflammatory activity using the carrageenan paw oedema and the croton oil ear test. "EPF (0.5 mg kg-1 i.v.) almost inhibited the carrageenan-induced oedema over 8 h and furthermore, EPF, topically applied, inhibited mouse ear oedema induced by croton oil." Reduction of the leukocytic infiltration of the croton oil dermatitis, evaluated both as peroxidase activity and histologically was observed.. EPF applied topically appeared to be slightly inferior in potency to indomethacin. It was concluded that the anti-inflammatory activity of E. angustifolia resides in its polysaccharidic content. ³⁴

An aqueous extract obtained from the roots of Echinacea angustifolia yielded 5 fractions which were separated on the basis of molecular weight. The fractions were evaluated topically for anti-inflammatory activity been in mice using the Croton oil ear test. The most active fraction in inhibiting the oedema (with a molecular weight between 30, 000 and 100, 000) also reduced the infiltration of inflammatory cells. "The activity of this fraction was comparable with that of a raw polysaccharidic extract obtained from E. angustifolia roots by differential solubility. The high-molecular weight polysaccharides are therefore proposed as the anti-inflammatory principles of the plant." ³⁵

Tumor Necrosis:

"USDA researchers have discovered a tumor-inhibiting principle in Echinacea, a oncolytic lipid-soluble hydrocarbon from the essential oil" ³⁶

"After therapy with Echinacea complex, no significant alteration in the production of the cytokines could be seen in comparison to the controls, and also the leukocyte populations remained constant." It was concluded that at the application and dosage used, the therapy with Echinacea complex has no detectable effect on tumor patients'' lymphocytes activity as measured by their cytokine production. ³⁷

Acidic arabinogalactan (AA), a highly purified polysaccharide from plant cell cultures of Echinacea purpurea was effective in activating macrophages to cytotoxicity against tumor cells and micro-organisms (Leishmania enriettii). AA induced macrophages to produce tumor necrosis factor (TNF-alpha), interleukin-1 (IL-1),and interferon-beta 2. AA did not activate B cells and did not induce T cells to produce interleukin-2, interferon-beta 2, or interferon-gamma, but slight increases in T-cell proliferation were observed. AA injected ip stimulated macrophages, "a finding that may have therapeutic implications in the defense against tumors and infectious diseases." ¹⁶

"Purified polysaccharides (EPS) prepared from the plant Echinacea purpurea are shown to strongly activate macrophages. Macrophages activated with these substances develop pronounced extracellular cytotoxicity against tumor targets." EPS alone brings caused this activation which was independent of any cooperative effect with lymphocytes. Activation with EPS caused the production and secretion of oxygen radicals and interleukin 1 by macrophages. "EPS has no effect on T lymphocytes. B lymphocytes show a comparatively modest proliferation after incubation with E. purpurea EPS." It was concluded that EPS compounds (which are at least in tissue culture completely nontoxic) may be suited to activate in vivo cells of the macrophage system to cytotoxicity. Relevance in tumor and infectious systems may be implied. ³⁸

Immune System/Chronic Fatigue Syndrome/Acquired Immunodeficiency Syndrome:

Very high doses (1,000 times greater than typically used) are said to be immunosuppressive. ¹⁵

 "In some studies (on Echinacea), immuno-compromised patients seemed to benefit the most. While provocative, interpretation of the results is limited in both of the RDBPC trials by inadequate use or description of the following: diagnostic criteria, randomization process, treatment interventions, methods for assessing outcome, assurance of blinding, detail of results, and quality statistical analysis." ³³

"An extract of echinacea showed an increase of 50%-120% in immune function over a 5 day period." ³⁹

Water- soluble plant extracts of Echinacea angustifolia, Echinacoside, was studied for cellular immunity properties in mice. "Under various conditions no effects on the immune system could be found using the carbon clearance test." ⁴⁰

"The reaction of the granulocytes--phagocytosis and therefore chemilumenescence—under the influence of echinacea extract depends on the doses and methods applied." Standardization of methods and investigations are necessary to prove the immunostimulative effect of so called immunotherapeutics. "Dose and method dependent single results cannot be a convincing justification for specific therapeutic medication" ⁴¹

Echinacea purpurea and Panax ginseng extracts were evaluated for their capacity to stimulate cellular immunity by peripheral blood mononuclear cells (PBMC) from normal individuals and patients with either the chronic fatigue syndrome or the acquired immunodeficiency syndrome. "Both echinacea and ginseng, at concentrations > or = 0.1 or 10 micrograms/kg, respectively, significantly enhanced NK-function of all groups." It was concluded that extracts of Echinacea purpurea and Panax ginseng enhance cellular immune function of PBMC both from normal and immunosuppressed individuals. ⁴²

Colds, Flu, and Respiratory Tract Infections:

"Only 2 RDBPC trials have evaluated E purpurea''s effect on upper respiratory tract infections. In one, echinacea extract demonstrated a statistically significant decrease in symptoms and duration of "flu-like" illness (n=180)." ⁴³

"The effects were dose dependent; benefits were noted beginning on day 3 or 4 in patients taking 180 drops (1 drop=20 µL) of extract daily, whereas volunteers taking 90 drops per day showed no benefit." In 108 volunteers who had a history of recurrent URIs, prophylactic echinacea extract showed a 14% relative risk reduction in both frequency and severity of recurrences. ⁴⁴

In a Three-armed, randomized, double-blind, placebo-controlled trial.study a prophylactic effect of the investigated echinacea extracts could not be shown. "However, based on the results of this and 2 other studies, one could speculate that there might be an effect of echinacea products in the order of magnitude of 10% to 20% relative risk reduction." Larger scale studies in the future were recommended to prove or disprove this effect. ⁴⁵

"180 patients were in a double blind placebo study on the effects of Echinacea for the treatment of colds. An extract of Echinacea @ 450 mg, Echinacea @900mg or a placebo was administered daily. There was a dose dependent reduction of symptoms with the patients receiving 900mg while those receiving 450mg showed no positive results over the placebo group. ^46.

"108 patients receiving either an extract of the fresh pressed juice of E. purpurea (4ml twice daily) or a placebo for eight weeks. The results were significant. Average length of time between infections was forty days with Echinacea, 35.2 % stayed healthy. Average length of time between infections for those patients on the placebo was 25.09 and only 25% stayed healthy." ⁴⁷

A randomized, double-blind, single-center clinical study examined the effect of the expressed juice of Echinacea purpurea (Echinagard*) in patients with initial symptoms of an acute, uncomplicated upper airway infection (common cold). Patients (120 Swedish adult furniture factory workers) enrolled had suffered from at least three respiratory infections within the previous 6 months. "Patients were randomized to receive either echinacea or placebo - 20 drops in a half glass of water every 2 hours for the first day and thereafter three times daily for up to 10 days." Subjective symptoms were recorded by patients who were interviewed by the attending physician about their symptoms and the course of illness. Patients taking echinacea reported less colds and got well faster. "Analysis of time to improvement found that patients taking echinacea showed a more rapid recovery than those taking placebo (p<0.0001)." Neither group reported any specific adverse events. "*The brand name Echinagard is used in Sweden for the Echinacin product manufactured by Madaus AG of Cologne, Germany. It is sold in the U.S. under the brand names EchinaGuard&trade; and EchinaGuard;Pro" ⁴⁸

"Echinacea purpurea, a plant originally used by native Americans to treat respiratory infections, was evaluated for its ability to stimulate the production of cytokines by normal human peripheral blood macrophages in vitro. Commercial preparations of echinacea fresh pressed juice and dried juice were tested at concentrations ranging from 10 micrograms/ml to 0.012 microgram/ml and compared to endotoxin stimulated and unstimulated controls" Concentrations of echinacea as low as 0.012 microgram/ml stimulated macrophages to produce significantly higher levels of IL-1, TNF-alpha, IL-6 and IL-10 (P < 0.05) than unstimulated cells. Such results of low levels of echinacea are consistent with an immune activated antiviral effect. The immune stimulatory ability of the unpurified fresh pressed juice of Echinacea purpurea was demonstrated and offer some insight into the nature of the resulting immune response as compared to endotoxin. ⁴⁹

The immunomodulatory activity of preparations containing extracts of Echinacea in 134 healthy volunteers was investigated in five placebo-controlled randomized studies . "Two studies tested intravenous homeopathic complex preparations containing Echinacea angustifolia D1 (study 1) and D4 (study 5). Two studies (2 and 3a) tested oral alcoholic extracts of roots of E. purpurea, one study an extract of E. pallida roots (study 3b), and one study an extract of E. purpurea herb (study 4)." Only studies 1 and 2 showed significantly enhanced phagocytic activity. No side effects were reported. It was suggested that future studies be performed on patients rather than healthy volunteers and that the echinacea be better standardized or chemically defined. ⁵⁰

Topical Uses/Wounds/Skin Damage/Radiation:

The high-molecular weight polysaccharides (30,000 to 100,000) of the aqueous extract of Echinacea angustifolia root were the most active in inhibiting the edema in mice using the Croton oil ear test and are therefore proposed as the anti-inflammatory principles of the plant." ⁵¹

"Of 4500 patients with inflammatory skin conditions, including psoriasis, 85% were cured with topical applications of echinacea salve." ⁵²

"These results indicate that this representative class of polyphenols of Echinacea species protects collagen from free radical damage through a scavenging effect on reactive oxygen species and/or C-, N-, S-centered secondary radicals, and provide an indication for the topical use of extracts from Echinacea species for the prevention/treatment of photodamage of the skin by UVA/UVB radiation, in which oxidative stress plays a crucial role. " ⁵³

"In experiments with mature Wistar male rats under irradiation by dose of 5 Gy the effect of emoxypine, citomedine and echinacea purpurea on the content of liposoluble vitamin A, carotene, vitamin E and its metabolites (quinone and oxidized to copherol) in blood plasma, spleen, liver and testes was studied."

All drugs mobilized the internal reserves of these vitamins. While possibly useful as radio protectors they exhaust the reserves of lipid soluble vitamins and should, therefore, be used in combination with vitamin preparations. ⁵⁴

Herpes:

Viracea, a topical microbicide, a blend of benzalkonium chloride and phytochemicals derived from Echinacea purpurea (a proprietary formula from Destiny BioMediX Corp) was tested against 40 strains of herpes simplex virus (HSV). "Although the active component(s) in Viracea that has anti-HSV activity is not known, it appears that this extract has good antiviral activity against both ACV resistant and ACV susceptible strains of HSV-1 and HSV-2." ⁵⁵

ANIMAL TOXICOLOGY

"Single oral or intravenous doses of the expressed juice of Echinacea purpurea(EP) proved virtually non-toxic to rats and mice. After 4 weeks of oral administration in doses amounting to many times the human therapeutic dose laboratory tests and necropsy findings gave no evidence of any toxic effects in rats. Tests for mutagenicity carried out in microorganisms and mammalian cells in vitro and in mice all gave negative results. In an in vitro carcinogenicity study EP did not produce malignant transformation in hamster embryo." ²⁷

 In a Benefit-Risk Assessment study an author cites data showing a lack of mutagenicity and a very low acute toxicity. ¹⁵

"Extracts of Viscum album (Plenosol) and Echinacea purpurea (Echinacin) are used clinically for their non-specific action on cell- mediated immunity. In vitro we could prove that these two extracts have a stimulating effect on the production of lymphokines by lymphocytes and in the transformation test. A toxic effect on cells was produced only with very high, clinically irrelevant concentrations. Clinical application of these extracts can produce a stimulation of cell-mediated immunity (one therapeutic administration followed by a free interval of one week) or can have a depressive action (daily administrations of higher doses). These observations were confirmed by lymphokine production and assay, 3H-thymidine incorporation and a skin test with recall antigens (Multitest Merieux)." ⁵⁶

Echinacea is an herb with a broad range of reported medical applications. It has been reported to improve the body’s defenses against viral and bacterial infections. It is used in the treatment of colds, influenza, and sore throats as well as other applications.

Echinacea should not be used in cases of HIV. ^4/10

Echinacea should not be used in cases of immune system dysfunction, autoimmune conditions (including systemic lupus) and progressive systemic conditions s.c. as multiple sclerosis, tuberculosis, leukosis, collagen disorders, and diabetes mellitus(injectable form of Echinacea). ^4/10

Herb substitutions and adulterations have been reported in products sold as Echinacea. Read labels carefully!

It may cause a mild tingling sensation to the tongue. Other adverse effects are rare.

Echinacea should not be used for longer than 3 to 8 consecutive weeks depending on the application and herb preparation.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

ECHINACEA (Echinacea sp.) - ORAL

USES: Echinacea has been used for virus infections such as the common cold and flu. It is used to strengthen the immune system. It has also been used for returning vaginal fungal infections ("yeast infections") along with antifungal products applied to the vaginal area.

Some herbal/diet supplement products have been found to contain possibly harmful impurities/additives. Check with your pharmacist for more details about the brand you use.

The FDA has not reviewed this product for safety or effectiveness. Consult your doctor or pharmacist for more details.

HOW TO USE: Take this product by mouth as directed. Follow all directions on the product package. If you are uncertain about any of the information, consult your doctor or pharmacist.

Prolonged use may lessen the effects of this product. It is recommended that this product be used for no more than 8 weeks at a time.

If your condition persists or worsens, or if you think you may have a serious medical problem, seek immediate medical attention.

SIDE EFFECTS: Nausea, numbness/tingling of the lips/tongue, and an unpleasant taste in the mouth may occur. If these effects persist or worsen, tell your doctor.

A very serious allergic reaction to this product is rare. Your risk of an allergic reaction is higher if you have asthma, frequent allergic reactions/skin rashes, or hay fever. Seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking echinacea, tell your doctor or pharmacist if you are allergic to it; or to plants in the Asteraceae/daisy family such as ragweed, chrysanthemums, marigolds, and daisies; or if you have any other allergies.

If you have any of the following health problems, consult your doctor or pharmacist before using this product: asthma, cancer, immune system problems (autoimmune disorders such as multiple sclerosis, rheumatoid arthritis, lupus), infection with HIV or tuberculosis, organ transplant.

Liquid forms of this product may contain sugar and/or alcohol. Caution is advised if you have diabetes, alcohol dependence, or liver disease. Ask your doctor or pharmacist about using this product safely. If there is alcohol in this product, it may make you dizzy or drowsy. Use caution while driving, using machinery, or taking part in any activity that requires alertness. (See also Drug Interactions section.) Limit alcoholic beverages.

During pregnancy, this product should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this product passes into breast milk. Breast-feeding while using this product is not recommended. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Tell your doctor of all prescription and nonprescription medication you may use, especially of: drugs that affect the immune system (e.g., azathioprine, cyclosporine, sirolimus, tacrolimus), corticosteroids (e.g., hydrocortisone, prednisone).

If your product contains alcohol, do not use it in combination with metronidazole or disulfiram.

This product may increase the effect of caffeine. Avoid drinking large amounts of beverages containing caffeine (coffee, tea, certain sodas) or eating large amounts of chocolate.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Keep all regular medical and laboratory appointments.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Refer to storage information printed on the package. If you have any questions about storage, ask your pharmacist. Keep all medications and herbal products away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.