Echinacea
This rediscovered American herb has shown efficacy
as an important natural immune-system stimulator.

Wendell Combest, Ph.D.
Associate Professor of Pharmacology

George Nemecz, Ph.D.
Assistant Professor of Biochemistry,
Dept. of Pharmaceutical Sciences,
Campbell University School of Pharmacy,
Buies Creek, NC

Echinacea, or purple coneflower, is an indigenous North American perennial. There are three species of medicinal value: Echinacea angustifolia, Echinacea purpurea and Echinacea pallida. There are a total of nine species of Echinacea that can be found from Canada to as far south as northern Texas. Echinacea purpurea is popular among gardeners because of its ease of cultivation and its large bright purple flowers that radiate out from a spiny flowering head or cone. The three species vary in size from the smaller E. angustifolia to the much denser and taller E. purpurea, which can reach a height of 5 feet.

The roots and aboveground parts of echinacea were widely used for their medicinal properties by many Native American tribes living in the upper Missouri Valley and Great Plains. Samples of echinacea have been excavated from archaeological digs dating as far back as 400 years. Early medicinal uses include treatment of coughs, colds, insect stings and animal bites, and many types of skin diseases. The so-called Eclectic physicians, who practiced a brand of herbal medicine in the U.S. from the mid 1800s until about 1930, learned about echinacea from the Native Americans. Soon it became among the most popular medicinal plants in the United States. Echinacea was included in the U.S. National Formulary from 1916 until 1950 but was never given an endorsement by the American Medical Association due to lack of scientific evidence of its effectiveness. With the decline of the Eclectics in the 1930s and the introduction of modern antibiotics, the widespread use of echinacea declined rapidly. Interest in this herb in the U.S. resurfaced in the 1970s, most likely as a part of the "back to nature" movement, and has risen sharply in the U.S. in the last five years.

Components of the Active Fractions

Analysis of the three most commonly used species of Echinacea has revealed many pharmacologically active compounds present in variable levels in roots and leaves and between species.1

Caffeic acid derivatives: Echinacoside is found in the roots of E. angustifolia and E. pallida but not E. purpurea. Other derivatives include cichoric and chlorogenic acids and cynarin. These constituents may play roles in stimulating phagocytosis.

Polysaccharides: Inulin and other high molecular weight polysaccharides such as heteroxylan, arabinogalactan, and fucogalactoxyloglucans stimulate macrophages and they possess anti-inflammatory activity.

Alkylamides: Echinacein and several isobutylamides are responsible for the local anesthetic effect and some of the anti-inflammatory activity of echinacea.

Essential oil components: These include humulene, echinolone, vanillin, germacrene and borneol. Several have insecticidal activities.

Other constituent groups include polyacetylenes, flavo-noids and glycoproteins, whose biological effects, if any, are presently unknown.

Medicinal Uses

Early uses of echinacea ranged from treating saddle sores in horses to snakebite and typhoid fever. Today echinacea’s popularity is fueled largely from an accumulating body of evidence supporting its efficacy as an immune-system stimulant. Perhaps its most frequent use is in reducing symptoms of the common cold and flu, especially at their onset or in the early stages of infection. The results of several clinical studies have shown that treatment with echinacea can reduce both the incidence of colds and flu as well as the severity and duration of the infections.2,3

Echinacea has been successful in treating many types of infectious diseases and conditions. Infections of the upper respiratory and urogenital tracts respond well to treatment with echinacea. Treatment of upper respiratory infections including colds, influenza, tonsillitis, otitis media, sore throat, and whooping cough accounts for the most widespread use of echinacea today. Many European studies, primarily done in Germany utilizing both injectable and orally administered echinacea preparations, support its therapeutic efficacy in these conditions. In Germany the use of echinacea has been approved as a supportive therapy to standard antimicrobial agents in the treatment of respiratory and urinary tract infections. Echinacea extracts have also been shown to reduce the growth of Trichomonas vaginalis and lower the recurrence rates of Candida albicans infections.4 A freshly pressed extract of E. purpurea enhanced the efficacy of a topical antimycotic agent (econazole nitrate, decreasing the incidence of recurrent infection from 60.5% to 5%–17%.5 Purified polysaccharides from E. purpurea cell cultures mediated protection against systemic infections with Listeria monocytogenes and Candida albicans in mice.6

The pharmacological mechanism underlying echinacea’s inhibitory effect on microbial infections relates to its stimulation of the body’s immune defense system rather than any significant direct antimicrobial action. However, the caffeic acid derivative echinacoside does have mild antibiotic properties, while other constituents possess weak antiviral as well as fungistatic activity.7 A major part of this immunostimulation by echinacea involves enhancement of macrophage phagocytosis as well as stimulation of their production and secretion of immune-potentiating substances such as interferon, interleukins, and tumor-necrosis factor (TNF).8 An E. purpurea extract was shown to increase the in vitro phagocytosis of Candida albicans by both granulocytes and monocytes from healthy donors by 30%–45%.9 The chemotactic migration of granulocytes was also increased.

In a recent study, extracts of E. purpurea were shown to stimulate both natural killer cell activity and antibody-dependent cellular cytotoxicity against human herpes virus.10 All of these studies utilized peripheral blood mononuclear cells isolated from both normal individuals and patients with depressed cellular immunity. Echinacea also promotes nonspecific T-lymphocyte activation with resultant increased cell replication and enhanced production of interferon and increases in antibody binding sites.11 An increased number of circulating neutrophils has also been reported. Echinacea also increases the amount of the serum protein properdin, which in turn stimulates the portion of the immune system known as the alternative complement pathway.12 Also a lipid-soluble compound isolated from echinacea roots (1,8 pentadecadiene) was shown to have direct antitumor activity.14 Of special interest is the finding that echinacea stimulates macrophages to attack and destroy tumor cells.13 In addition to these anticancer effects, several studies found that echinacea is especially useful in increasing the white blood cell count in cancer patients receiving radiation or chemotherapy.15

The wound-healing effect of echinacea has been recognized since its early use in treating animal bites and gunshot wounds. This beneficial effect is at least partially explained by many studies showing an inhibition of the enzyme hyaluronidase by polysaccharide and alkylamide fractions from echinacea root extracts.16 This enzyme is produced by many wound-invading microorganisms and functions to break down hyaluronic acid, which is important in holding cells together in a tissue. By preventing the breakdown of this "cellular cement," invading microorganisms are prevented from spreading throughout the tissue. There is also evidence that echinacea can directly stimulate fibroblasts, thus enhancing the production of hyaluronic acid and other compounds needed for tissue repair.17 Several clinical studies have been reported demonstrating echinacea’s wound-healing effects. The largest study involved 4,598 patients treated with a salve made from E. purpurea leaves and flowers. The results of this study indicated an 85% success rate in the treatment of various skin conditions such as abscesses, eczema, burns, varicose ulcers of the leg, and a variety of skin wounds.12

Much of echinacea’s often reported anti-inflammatory activity is most likely due to its inhibition of hyaluronidase and its resultant changes in the inflamed tissue and prevention of the spread of the infection. However, the inhibition by polysaccharides and alkylamides of cyclooxygenase and 5-lipoxygenase is also important. These enzymes utilize arachidonic acid and enhance the production of prostaglandins and leukotrienes, which are powerful inflammatory mediators known to be involved in many chronic inflammatory conditions such as arthritis.18 Echinacea’s anti-inflammatory activity has been useful in the treatment of rheumatoid arthritis.1 In this study, freshly pressed use of E. purpurea given three times a day resulted in a 22% decrease in inflammation compared to a 49% decrease with prednisone. No side effects were noted in patients using echinacea, whereas there were many with the use of prednisone.

Preparations

Tea made from powdered or ground roots or dried leaves are the most inexpensive echinacea preparations. Dried echinacea roots and leaves can be formulated into capsules or tablets. Capsules are less stable than tablets due to the increased surface exposure to oxidation. Alcoholic extracts or tinctures are the most commonly used preparations in the U.S. They are stable for up to three years when protected from light and extreme temperatures. Ointments and salves containing root or leaf extracts are also available for topical application in the treatment of wounds and skin diseases. Prior to 1988 many commercially available echinacea products were adulterated with Parthenium integrifolium, a less expensive plant.1 Dosages used vary widely depending upon the plant source utilzed and the condition treated. Typical dosages used to stimulate immune function during a cold or flu would be 3–4 mg of a 1:5 tincture in 1 g of dried powder in capsules or as a tea in one cup of water. These doses would be given 3 times a day for up to 10 days. Most of the German clinical studies over the past 10 years have utilized an injectable preparation of fresh stabilized extract of E. purpurea known as Echinacin. A purified polysaccharide fraction from cultured E. purpurea cells was used in many of these studies. Since injectable preparations are not available in the U.S., comparing German clinical results with any other data should be done with caution. Some attempts have been made by European manufacturers to standardize echinacea products such as Esberitox, which is standardized to certain glycoproteins.

Side Effects and Toxicity

The long history of echinacea use and numerous animal toxicity studies attest to its safety. No harmful reactions have been reported when echinacea is used as recommended. Toxicity studies in rats show the lack of toxic effects following four weeks of daily injections of Echinacin at doses many times the therapeutic dose in humans.20 Tests for mutagenicity in microorganisms and mammalian cells were negative. [Editor’s note: Because some of these studies used animals and others involved in vitro testing, comparison of results is difficult.] Despite an excellent safety record, individuals with known allergies to plants in the Daisy family should be cautious. Prolonged administration of echinacea may lead to immune-system overstimulation and eventual suppression.1

REFERENCES

  1. Hobbs C. Echinacea: The Immune Herb. Second Edition. Botanic Press. Santa Cruz, CA, 1996.
  2. Schoneberger D. The influence of immune-stimulating effects of pressed juice from Echinacea purpurea on the course and severity of colds. Results of a double-blind study. Forum Immunologie.1992;8:2-12.
  3. Braunig B. Echinacea purpurea radix for strengthening the immune response in flu-like infections. Z Phytother. 1992;13:7-13.
  4. Samochowiec E. et al. Evaluation of the effect of Calendula officianalis and Echinacea angustifolia extracts on Trichomonas vaginalis in-vitro. Wiad Parazytol 1979;25(1):77-81.
  5. Coeugniet EG, Kuhnast R. Recurrent candidiasis: adjunct immunotherapy with different formulations of Echinacea. Therapiewoche 1986;36:3352-8.
  6. Roesler J, et al. Application of purified polysaccharides from cell cultures of the plant Echinacea purpurea to mice mediates protection against systemic infections with Listeria monocytogenes and Candida albicans. Int J Immunopharm 1991;13:27-37.
  7. Stoll A, et al. Antibacterial substances II. Isolation and constitution of echinacoside, a glycoside from the roots of Echinacea angustifolia.Helv Chim Acta 1950;3:1877-93.
  8. Bauer R, et al. Immunological in vivo and in vitro examinations of Echinacea extracts. Arzneim Forsch 1988;38:276-81.
  9. Wildfeuer A, Mayerhofer D. The effect of plant preparations on cellular functions in body defense. Arzneim Forsch 1994;44(3):361-6.
  10. Broumand N, et al. In vitro effects of echinacea and ginseng on natural killer and antibody-dependent cell cytotoxity in healthy subjects and chronic fatigue syndrome or acquired immunodeficiency syndrome patients. Immunopharm 1997;35(3):229-235.
  11. Wagner V, et al. Immunostimulating polysaccharides (heteroglycans) of higher plants. Arzneim Forsch 1985;35:1069-75.
  12. Bauer R, Wagner H. Echinacea species as potential immunostimulating drugs. Econ Med Plant Res 1991;5:253-321.
  13. Stimpel M, et al. Macrophage activation and induction of macrophage cytotoxicity by purified polysaccharide fractions from the plant Echinacea purpurea. Infection and Immunity 1984;46(3)845-849.
  14. Voaden D, Jacobson M. Tumor inhibitors. Identification and synthesis of an oncolytic hydrocarbon from American coneflower roots. J Med Chem 1972;15:619-23.
  15. Phohl P. Therapy of radiation-induced leukopenia by Esberitox. Med Klin 1969;64:1546-7.
  16. Busing K. Hyaluronidase hem mung durch echinacin. Arzneim Forsch 1952;2:467-9.
  17. Koch F, Uebel H. Experimentelle untersuchungen uber den ein flur von Echinacea purpurea auf das hypophysennebennierenrinden-system Arzneim Forsch 1953;133-7.
  18. Wagner H. et al. In vitro inhibition of arachidonate metabolism by some alkamides and phenylated phenols. Planta Medica 1989;55:566-7.
  19. Seidel K, Knobloch H. Nachweis und vergleich der antiphlogischen wirkung antirheumatischer medikamente. Z fur Rheum 1957;16:231-8.
  20. Mengs U, et al. Toxicity of Echinacea purpurea. Acute, subacute and genotoxicity studies. Arzneim Forsch 1991;41(10):1076-1081.
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