Echinacea

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Echinacea spp.

Echinacea purpurea (L.) Moench, E. pallida (Nutt.) Nutt., E. angustifolia DC.

[Fam. Asteraceae]

Overview

The medicinal plant echinacea, indigenous to the U.S., is one of the most popular herbs in the U.S. marketplace. The roots of several species were the most widely used medicines of Native Americans of the Great Plains. Ethnobotanist M.R. Gilmore noted, “Echinacea seems to have been used as a remedy for more ailments than any other plant” (Gilmore, 1911). Foster (1991) and Moerman (1998) have reviewed the ethnobotany of both the roots and leaves of various species of Echinacea. They were used by Native Americans for toothache, enlarged glands (mumps), sore throat, snakebite, coughs, burns, and as an analgesic. Eclectic medical physicians of the late 19th century employed E. angustifolia root for a variety of indications, both internally and externally, including sepsis (e.g., gangrene, boils, septicemia), foul mucous discharges, cancerous growths, typhoid, various types of fevers, and locally applied for chronic skin sores (Felter and Lloyd, 1898). They also used it for mitigation of the pain of gonorrhea and syphilis, as a local anesthetic, for snakebite and other venomous stings (Foster, 1991). 

Preparations made from several plant species and plant parts of the genus Echinacea constituted the top-selling herbal supplement sold in all U.S. channels of sales (mass market, multilevel, and natural food stores) in 1997, consisting of 9% of the total market based on $3.6 billion in total sales (Brevoort, 1998). In 2000, echinacea preparations ranked fourth in the mainstream market with retail sales of $58,422,932 (Blumenthal, 2001). While the main constituents of the different species and plant parts have pharmacological activity, the exact compounds responsible for echinacea’s therapeutic value are unclear. For this reason, it is important to note the taxonomic source, plant part, and type of preparation for each clinical study (Parnham, 1999; Bauer 1999; Melchart and Linde, 1999).

Description

Nine species of the genus Echinacea have been classified taxonomically (Hobbs, 1994) although recent chemical and genetic research suggests possible reclassification of the genus to four species (Binns et al., 2002). Echinacea preparations consist of any one or more of the plant parts from three Echinacea species [Fam. Asteraceae], including the fresh, above-ground parts (harvested at the time of flowering), the fresh or dried root of E. purpurea (L.) Moench, and the fresh or dried root of E. pallida (Nutt.) Nutt., and/or E. angustifolia D.C., and their preparations in effective dosage. Occasionally, the fresh or dried above-ground parts of E. pallida, collected at the time of flowering, are used but are often labeled incorrectly as “E. angustifolia” in the marketplace (Blumenthal et al., 2000).

Primary Uses

Respiratory

Treatment of symptoms and duration in upper respiratory tract infections (URTIs)

E. purpurea herb and root (Brinkeborn, 1998; Hoheisel et al., 1997; Bräunig et al, 1992)

E. pallida root (Dorn et al., 1997)

E. angustifolia root (Galea et al., 1996)

E. purpurea and E. angustifolia stems and E. purpurea root (Lindenmuth and Lindenmuth, 2000)

E. purpurea and E. pallida roots (Henneicke-von Zepelin et al., 1999; Reitz et al., 1990; Vorberg, 1984)

Other Potential Uses

Internal

Immune system stimulant

E. purpurea (Berg et al., 1998; Brinkeborn, 1999; Hoheisel et al., 1997; Braunig et al., 1992)

E. pallida (Dorn et al., 1997)

Adjunct therapy in chronic candidiasis in women

E. purpurea (Coeugniet and Kuhnast et al., 1986)

Prevention of URTIs

E. purpurea (Grimm and Müller, 1999; Schöneberger et al., 1992)

E. angustifolia (Melchart et al, 1998)

E. purpurea and E. pallida (Forth et al., 1981)

E. angustifolia herb and root combination (Schmidt et al., 1990)

External

Wound healing

E. purpurea (Blumenthal et al., 1998; WHO, 1999)

E. pallida root (Speroni et al., 1998)

E. angustifolia root (Bradley, 1992)

Dosage

Internal

Crude Preparations

E. purpurea herb

Juice: 6–9 ml daily expressed juice from fresh E. purpurea aerial parts 2.5:1, stabilized in 22% alcohol, (Bauer and Liersch, 1993; Blumenthal et al., 1998).

Infusion: For upper respiratory and flu symptoms, 150–240 ml boiling water poured over about 1 g dried herb and steeped covered, for 10–15 minutes, 5–6 times daily (Lindenmuth and Lindenmuth, 2000).

Tincture: 5 drops, 1–3 times daily 1:10 (w/v), in 65% (v/v) alcohol. For acute conditions, 5 drops every 1/2–1 hour (Bauer and Liersch, 1993).

E. purpurea, E. pallida, E. angustifolia root

Dried root: 0.9–1 g (approximately 900 mg) cut root, 3 times daily.

Infusion: 0.9 g root in 150 ml boiled water steeped for 10 minutes, several times daily between meals (Bauer and Liersch, 1993; Wichtl and Bisset, 1994).

Decoction: 1 g in 150 ml water boiled for 10 minutes, 3 times daily (Bradley, 1992).

Fluid extract: 1:1 in 45% alcohol, 0.5–1.0 ml 3 times daily (Newall et al., 1996; Bradley, 1992).

Tincture:  1:5 (g/ml), ethanol 55% (v/v) 30–60 drops, approximately 1.5–5 ml (Bradley, 1992), three times daily (Bauer and Liersch, 1993; ESCOP, 1999).

External

Crude Preparations

Ointment: Semisolid preparation containing at least 15% pressed juice in a base of petroleum jelly or anhydrous lanolin, and vegetable oil applied locally (Blumenthal et al., 1998; Blumenthal et al., 2000).

Poultice: Semisolid paste or plaster containing at least 15% pressed juice, applied locally (Blumenthal et al., 2000).

Duration of Administration

Internal and External

The German Commission E recommended use for no longer than eight weeks (Blumenthal et al., 1998). Note: This duration limit has been misinterpreted as meaning that echinacea preparations may not be safe for use for longer than eight weeks, but this is not the case. This restriction was adopted by the Commission E due to its opinion that most conditions for which echinacea preparations are to be used are usually relatively minor and transient. Therefore, if therapy with echinacea has not succeeded within eight weeks, and symptoms still persist, more aggressive treatment is presumably needed.

Chemistry

The constituents of echinacea preparations vary depending on the particular species and plant part used.

E. purpurea herb (i.e., aerial parts) and root both contain caffeic acid derivatives (0.6–2.1% in roots), including mainly cichoric acid (1.2–3.1% in the flowers), caffeic acid, caftaric acid, chlorogenic acid and 0.001–0.04% alkamides. E. purpurea herb also contains water-soluble polysaccharides (arabinoxylan and arabinogalactan types); fructans; 0.48% flavonoids of quercetin and kaempferol type; and 0.08–0.32% essential oil (Bauer, 1999; Bauer and Liersch, 1993). E. purpurea root differs in containing polyacetylene derivatives; polysaccharides (fructosans, arabinogalactans); glycoproteins comprised of approximately 3% protein, of which the dominant sugars are 64–84% arabinose, 1.9–5.3% galactose, and 6% glucosamine, and up to 0.2% essential oil (Bauer 1999; Bauer and Liersch, 1993; ESCOP, 1999; Pietta et al., 1998).

E. pallida herb contains caffeic acid derivatives including cichoric acid, caftaric acid, echinacoside, verbascoside, chlorogenic acid, and isochlorogenic acid; flavonoids (mainly rutoside); alkamides; and <0.1% essential oil (Bauer, 1998; Bauer and Liersch, 1993; Leung and Foster, 1996; Pietta et al., 1998).

E. pallida root contains caffeic acid derivatives, mainly 0.7–1.0% echinacoside, followed by isochlorogenic acid, 6–O-caffeoylechinacoside, and chlorogenic acid; 0.2–2.0% essential oil comprised mainly of ketoalkynes and ketoalkenes, polyacetylenes, polysaccharides, and glycoproteins (Bauer, 1999; Bauer and Liersch, 1993; ESCOP, 1999; Pietta et al., 1998). Methyl jasmonate, a naturally-occurring cellular signal molecule, increased content of alkamides and ketoalene/ynes (Binns, 2001).

E. angustifolia herb contains caffeic acid derivatives such as cichoric acid, echinacoside, verbascoside, chlorogenic acid, and isochlorogenic acid; flavonoids (mostly quercetin); alkamides; polysaccharides; and less than 0.1% essential oil (Bauer, 1998; Bauer and Liersch, 1993; Leung and Foster, 1996; Pietta et al., 1998).

E. angustifolia root contains caffeic acid derivatives, mainly 0.3–1.7% echinacoside, followed by chlorogenic acid; an isochlorogenic acid and its characteristic constituent, cynarin; polysaccharides, including 5.9% inulin; glycoproteins comprised of approximately 3% protein, of which the dominant sugars are 64–84% arabinose, 1.9–5.3% galactose, and 6% glucosamines; 0.01–0.15% alkamides; and less than 0.1% essential oil (Bauer, 1998; Bauer, 1999; Bauer and Liersch, 1993; Pietta et al., 1998).

Pharmacological Actions

Echinacea’s pharmacological activity is believed to result from the combined effect of several of its chemical constituents, found within the different species and parts of echinacea.

Internal

Human

E. angustifolia

Promotes immunomodulatory activity (Melchart et al., 1994).

E. pallida

Exhibits immunomodulatory (Melchart et al., 1994) and immunostimulant activity (Dorn et al., 1997).

E. purpurea

Demonstrates immunomodulatory (Melchart et al., 1994); immunostimulant (Berg et al., 1998; Braunig et al., 1992; Brinkeborn, 1999; Hoheisel et al., 1997; Parnham, 1996); and antimycotic activity (Coeugniet and Kuhnast, 1986).

Animal

E. angustifolia and E. pallida

Demonstrate antitumor activity (Voaden et al., 1972) in combination with Thuja occidentalis tips and Baptisia tinctoria rhizome (per oral application).

E. purpurea

Increases phagocytosis (Bauer, 1999; Roesler et al., 1991; Wagner et al., 1988; Mose, 1983); increases serum leukocytes (Bauer, 1999); stimulates granulocyte migration (Roesler et al., 1991; Wildfeuer and Mayerhofer, 1994); stimulates cytokine production (Bauer, 1999; Burger et al., 1997; Wagner et al., 1985); protective effects on influenza A-virus infection in mice (Bodinet, 1999).

In vitro

E. purpurea

Enhances phagocytosis (Bauer, 1999); increases NO-production of macrophages (Bodinet, 1999); demonstrates natural killer cell action (See et al., 1997); and enhances the cytotoxicity of macrophages against tumor cells (Stimpel et al., 1984).

E. purpurea, E. angustifolia, E. pallida

Enhances antibody production (IgM, number of antibody-producing cells) (Beuscher et al., 1995; Bodinet, 1999); induces cytokine production (IL-1, IL-6, TNFa, IFNab) (Beuscher et al., 1995).

External

Human

E. angustifolia

Promotes wound-healing for skin inflammation and abrasions (Boon and Smith, 1999).

E. purpurea

Increases total lymphocyte count with a decreased percentage of T-helper cells in patients with eczema, neurodermatitis, candida, and herpes simplex (Boon and Smith, 1999).

E. purpurea, E. angustifolia, E. pallida

Protect against photodamage (Facino et al., 1995).

Animal

E. pallida and E. angustifolia

Inhibit inflammation (Speroni et al., 1998; Tubaro et al., 1987; Tragni et al., 1985).

E. pallida

Demonstrates cicatrizing and vulnerary activity (Speroni et al., 1998).

Mechanism of Action

Although the mechanism of action for Echinacea spp. is not fully understood, the following are proposed:

Binds polysaccharides to carbohydrate receptors on the cell surface of T-cell lymphocytes and macrophages (Wagner et al., 1984; Mose et al., 1983).

Promotes tissue regeneration and reduces inflammation by inhibiting hyaluronidase production (Tragni et al., 1985).

Generates oxidative burst and selective cytokine production in macrophages, leading to specific toxicity to tumor cell lines (Luettig et al., 1989; Stimpel et al., 1984).

A combination of three polysaccharides from E. purpurea cell cultures produced a substantial increase in the number of peripheral blood leukocytes, due to an increase in polymorphanuclear cells (PMNs) in mice (Roesler, 1991).

Enhances phagocytosis by human neutrophils in vitro and in human studies (Mose, 1983; Parnham, 1996).

Contraindications

Internal

Individuals with an increased tendency to have allergies, especially allergies to members of the family Asteraceae including arnica (Arnica spp.) flower, chamomile (Matricaria spp.) flower, marigold (Calendula officinalis L.) flower, yarrow (Achillea spp.) flower (Braun et al., 1996); ragweed (Ambrosia spp.); asters (Aster tataricus); and chrysanthemum (Chrysanthemum spp.) (Blumenthal et al., 2000). The Commission E noted that progressive systemic diseases such as tuberculosis, leukosis, collagenosis, multiple sclerosis, Acquired Immune Deficiency Syndrome (AIDS), Human Immunodeficiency Virus (HIV) infection, and other autoimmune diseases are contraindicated (Blumenthal et al., 1998), though these cautions were made based on theoretical considerations and not on reports of adverse findings (Bone, 1997–98).

External

None known (Blumenthal et al. 1998).

Pregnancy and Lactation: The Commission E found no known restrictions (Blumenthal et al., 1998). Although consumption of most medications and herbs is contraindicated during the first trimester, one recent controlled trial showed no evidence of increased risk for pregnant women who consumed echinacea (E. angustifolia and E. purpurea) (Gallo et al., 2000).

Adverse Effects

There are few reported adverse effects for internal and external applications. Aanaphylaxis has been reported with ingestion of an echinacea preparation made of E. angustifolia (whole plant) and E. purpurea root (Mullins, 1998; Mullins and Heddle, 2002). It is possible that pollens might be present in echinacea preparations made with aerial parts and not in those preparations containing root material only. Note: One source suggests that hepatotoxic effects have been reported with the persistent use of echinacea, causing one source to caution against the simultaneous use of echinacea with known hepatotoxic agents (e.g., anabolic steroids, amiodarone, methotrexate, or ketoconazole) (Miller, 1998). However, the significance of this purported hepatotoxicity is questionable, since echinacea lacks the 1, 2 unsaturated necine ring system associated with hepatotoxic pyrrolizidine alkaloids (PAs) (Roeder et al., 1984). PAs do not constitute a significant part of echinacea chemistry, and those PAs found in echinacea species are not of the saturated type. No known documentation of hepatotoxicity is associated with ingestion of echinacea.

Drug Interactions

The Commission E stated that there are no known interactions (Blumenthal et al., 1998). Several sources raise the issue of potential interactions with immunosuppressive drugs (e.g., cyclosporine and corticosteroids), but to date these concerns are speculative and lack clinical documentation (Brinker, 2001).

American Herbal Products Association (AHPA) Safety Rating

Class 1: Herbs that can be consumed safely when used appropriately (McGuffin et al., 1997).

Regulatory Status

Austria: The combination E. purpurea and E. pallida root, Thuja occidentalis herb, and Baptisia tinctoria root is approved as a nonprescription drug.

Canada: When labeled as a Traditional Herbal Medicine (THM) or as a homeopathic drug, echinacea root (E. angustifolia, E. pallida, E. purpurea) is regulated as a nonprescription drug, requiring premarket registration and assignment of a Drug Identification Number (DIN) (Health Canada, 1990, 1997, 2000; WHO, 1998).

France: The homeopathic mother tincture of the whole fresh plant, 1:10 (w/v) in 55% alcohol, is official in the French Pharmacopoeia (Ph.Fr.X) (Bauer and Liersch, 1993).

Germany: Approved by Commission E as a nonprescription drug (E. purpurea herb and E. pallida root) (Blumenthal et al., 1998). The combination of E. purpurea and E. pallida root, Thuja occidentalis herb, and Baptisia tinctoria root has not yet been approved as a nonprescription drug. The homeopathic mother tincture of the whole fresh plant (E. angustifolia or E. pallida) or aerial parts (E. purpurea) and dilutions are official in the German Homeopathic Pharmacopoeia (HAB, 2000).

Sweden: Classified as a natural remedy, intended for self-medication, requiring advance application for marketing authorization (MPA, 2001; Tunón, 1999; WHO, 1998). A monograph for Echinagard^® (Echinacin^®) is published in the Medical Products Agency (MPA) “Authorised Natural Remedies” (MPA, 1997).

Switzerland: Echinacea anthroposophical, homeopathic, and phytomedicines have positive classification (List D) by the Interkantonale Konstrollstelle für Heilmittel (IKS) and corresponding sales category D, with sale limited to pharmacies and drugstores, without prescription (Morant and Ruppanner, 2001; Codex, 2000/01; WHO, 1998).

U.K.: Herbal medicine in General Sale List, Schedule 1 (medicinal products requiring a full Product License), Table A (for internal or external use) (Bradley, 1992).

U.S.: Dietary supplement (USC, 1994). Homeopathic mother tincture, 1:10 (w/v) in 55% alcohol (v/v), is a Class C over-the-counter (OTC) drug official in the Homeopathic Pharmacopoeia of the United States (1991), Official Compendium (1992). Rhizome with roots, powdered root and powdered extract are subjects of botanical monographs in development for the USP-NF. Previews of the standards development were published in Pharmacopeial Forum (USP, 2002).

Clinical Review

Twenty-one studies are outlined in the following table “Clinical Studies on Echinacea,” including a total of 3,508 participants. All but three of these studies (Galea and Thacker, 1996; Melchart et al., 1998; Vonau et al., 2001), demonstrated positive effects for indications including cold, flu, upper respiratory tract infections (URTIs), candidiasis, and gestational safety. Five positive randomized, double-blind, placebo-controlled (R, DB, PC) studies, involving a total of 825 subjects, supported the use of echinacea monopreparations for the treatment (incidence, severity, and/or duration) of acute upper respiratory or flu-like infections (Brinkeborn et al., 1998, 1999; Dorn et al., 1997; Hoheisel et al., 1997; Bräunig et al., 1992). The acute treatment was further supported by six additional R, DB, PC studies using combination preparations of echinacea and other herbs (Lindenmuth and Lindenmuth, 2000; Henneicke-von Zepelin et al., 1999; Reitz et al., 1990; Dorn 1989; Vorberg and Schneider, 1989; Vorberg, 1984). One R, DB, PC study on an echinacea monopreparation did not find measurable benefit for treatment of URTI symptoms, though this may be due to the low dose and lack of severity of the symptoms (Galea and Thacker, 1996).

The prevention of URTIs was studied in a total of five R, PC studies with a total of 1,209 subjects, focused on the use of distinct monopreparations (Grimm and Müller, 1999; Melchart et al., 1998; Schöneberger, 1992) and unique combination products (Schmidt et al., 1990; Forth and Beuscher, 1981). Two of these studies concluded that echinacea did not significantly prevent URTIs. In the Melchart (1998) study, the treatment was administered noncontinuously, which may have been a factor in the lack of positive results, although the authors attributed the results to a subject group that was smaller than desired. Grimm and Muller (1999) reported that the “treatment with fluid extract of Echinacea purpurea did not significantly decrease the incidence, duration or severity of colds and respiratory infections compared to placebo.”

Other trials included a study on genital herpes that found no demonstrated effect (Vonau et al., 2001). One R, PC study on immunology in athletes, concluded that the echinacea group had no URTIs compared to placebo (Berg et al., 1998). Women using echinacea drops as an adjunct therapy in the treatment of chronic candidiasis showed a reduced recurrence rate (Coeugniet and Kuhnast et al., 1986). A prospective, controlled study on the safety of echinacea during pregnancy found no statistical difference between the groups (Gallo et al., 2000).

A review of 13 R, DB, PC trials studying the treatment and prevention of URTIs, evaluated the effectiveness of orally ingested echinacea preparations (Barrett et al., 1999). The authors concluded that the published trials suggest echinacea may be beneficial for treatment, but the variation of preparations and compositions (including combination products containing other botanicals) makes recommending specific doses problematic. They claimed that there was little evidence supporting the prolonged use of echinacea for prevention of URTIs (Barrett et al., 1999). An assessment of the methodology of 26 controlled clinical trials concluded that the published clinical studies suggest that some preparations containing echinacea can be efficacious as immunomodulators. However, the evidence is insufficient to recommend an exact dosage or specific preparation for use (Melchart et al., 1994). A review by Bone (1997-1998) observed that despite contraindications in auto-immune diseases based on theoretical considerations (e.g., those suggested by Commission E), current clinical use and scientific evidence do not support limitations on long-term use of echinacea with particular auto-immune diseases. Bone suggested echinacea should be considered an immunomodulator rather than an immunostimulant.

Branded Products*

Echinacea Plus^®: Traditional Medicinals^®, Inc. / 4515 Ross Road / Sebastopol, CA 95472 U.S.A. / Tel: (707) 823-8911 / Fax: (800) 886-4349 / www.traditionalmedicinals.com. Each tea bag 1,095 mg of the flowering aerial parts of E. purpurea and E. angustifolia, 30 mg of Echinacea purpurea extract (6:1) and flavor components lemongrass leaf and spearmint leaf.

Echinacin^®: Madaus AG / Ostermerheimer Strausse 198 / Köln, Germany / Tel: +49-22-18-9984-76 / Fax: +49-22-18-9987-21 / Email: b.londener@madaus.de. Expressed juice of the aerial parts of Echinacea purpurea, stabilized with 22% ethanol, by volume.

Echinaforce^®: Bioforce AG / CH-9325 Roggwil TG/ Switzerland / Tel: +41 71 454 61 61 / Fax: +41 71 454 61 62 / E-mail: Info@bioforce.ch / www.bioforce.com. Each tablet contains 400 mg dried extract, concentrated from a hydroalcoholic mother tincture (1:10) of E. purpurea herb fresh-flowering tops (380 mg) and E. purpurea root (20 mg), plus inert excipients materials.

EchinaGuard^®: Nature’s Way Products, Inc. / 10 Mountain Spring Parkway / Springville, Utah 84663 / U.S.A. / Tel: (801) 489-1500 / www.naturesway.com. Expressed juice of the aerial parts of Echinacea purpurea, stabilized with 22% ethanol, by volume.

Esberitox^® (prior to 1985): Schaper and Brümmer GmbH & Co. KG / Bahnhofstrasse 35 / 38259 Salzgitter / Ringelheim / Germany / Tel: +49-5341-30-70 / Fax: +49-5341-30-71-24 / Email: info@schaperbruemmer.de / www.schaper-bruemmer.com. Ethanolic extract of 7.5 mg of extracts of E. purpurea and E. pallida root (1:1), 2 mg of Thuja occidentalis herb, and 10 mg Baptisia tinctoria root and homeopathic dilutions of Apis mell. (D4), Crotalus (D6), Lachesis (D4), and Silicea (D4).

Esberitox^® N1 Tablets (1985 formulation based on Esberitox^®): Schaper and Brümmer GmbH & Co. KG. 7.5 mg of extracts of E. purpurea and E. pallida root (1:1), 2 mg of Thuja occidentalis herb, and 10 mg Baptisia tinctoria.

Esberitox^® N2 Tablets (1990 formulation based on Esberitox^® N1): Schaper and Brümmer GmbH & Co. KG. 7.5 mg of E. purpurea and E. pallida root (1:1), 2 mg of Thuja occidentalis herb, and 10 mg Baptisia tinctoria root. Subsequently changed sources of echinacea.

Resistan^®: TRUW Arzneimittel Vertriebs GmbH / Ziethenstrasse 8 / 33330 Gutersloh / Germany / Tel: +49-52-41-3007-40 / www.truw.de. Each 100 mg of Resistan^® contains: 12 g Echinacea angustifolia; 2.9 g Eupatorium perfoliatum; 2 g Baptista tinctoria; 2 g Arnica montana D2. Contains 13 vol. percent. (Note: this product is being reformulated and may change names.)

* American equivalents, if any, are found in the Product Table beginning on page 398.

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