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Echinacea (Echinacea)

Synonyms / Common Names / Related Terms
Alkamides, American coneflower, Asteraceae (family), black sampson, black susan, cichoric acid and polysaccharides, cock-up-hat, combflower, Echinacea angustifolia, Echinacea pallida, Echinacea Plus, Echinacea purpurea, Echinacin®, Echinacin® EC31, Echinaforce®, Echinaforce® Forte, Echinaguard®, Echinilin® (Factors R & D Technologies, Burnaby, British Columbia, Canada), hedgehog, igelkopf, Indian head, Kansas snake root, kegelblume, narrow-leaved purple coneflower, Pascotox®, purple coneflower, red sunflower, rudbeckia, SB-TOX, scurvy root, snakeroot, solhat, sun hat.

Mechanism of Action
  • Constituents: Alkamides are suspected to contribute to the activity of echinacea preparations. They are mainly derived from undeca- and dodecanoic acid and differ in the degree of unsaturation and the configuration of the double bonds.18
  • Antimicrobial effects: Echinacea may possess microbiocidal activity against Candida albicans, Listeria monocytogenes19, influenza virus20, vesicular stomach virus, and herpes simplex virus (HSV-1 and HSV-2)21. The relevance of these in vivo findings remains unclear.
  • Antineoplastic effects: Constituents of the root oil of Echinacea angustifolia and Echinacea pallida have been shown to possess antitumor activity in vivo.7
  • Antioxidant effects: Echinacea belongs to a class of antioxidants.1,2,3,4,5,6 Proposed mechanisms of antioxidant activity of extracts derived from echinacea roots include free radical scavenging and transition metal chelating.2
  • Cardiovascular effects: The effects of Echinacea purpurea on electrocardiographic and blood pressure were evaluated, and a single 350mg dose of had no effect on these measurements.22
  • Cytochrome P450 effects: The effects of echinacea on cytochrome P450 activity appear to be minor. However, further study into the interaction potential is merited.8 In lab tests, echinacea has both mildly inhibited and induced CYP3A4 activity.9 Echinacea reduced the oral clearance of substrates of CYP1A2 but not the oral clearance of substrates of CYP2C9 and CYP2D6.15 Echinacea selectively modulated the catalytic activity of CYP3A at hepatic and intestinal sites.15
  • Eye effects: Systemic echinacea has been shown to be effective in the control of low-grade autoimmune idiopathic uveitis. However, the exact mechanism is unclear.13
  • Immune system effects: Immunostimulatory properties of echinacea appear to target both non-specific and specific immune function. Non-specific effects include increases in macrophage proliferation and phagocytosis, as well as secretion of interferon, tumor necrosis factor, and interleukin-1 (in vitro and in vivo).23,24,25,26,27,28,29,30,1,31 Specific immune responses include the activation of alternate complement pathway components and elevated levels/activity of T lymphocytes and natural killer (NK) cells.32,33,34,11,35 The echinacea species Echinacea purpurea is believed to have the strongest potency on the immune system.36 Immunostimulation may depend on the dosage and frequency of administration. Cell-mediated immunity may be stimulated by one therapeutic administration followed by a "free" interval of one week, but can be depressed by the daily administration of higher doses.14 Other studies have failed to elicit these responses.17 Goel et al. conducted a randomized, double-blind, placebo controlled trial to assess the effect of Echinilin®, a formulation prepared from Echinacea purpurea, on the distribution of systemic leukoctes and the free radical production capacity of neutrophils. Additionally, the effects of this treatment on the activity of red blood cell superoxide dismutase, an antioxidant defense enzyme, was also determined.10 After two days of treatment, both groups demonstrated an increase in total white blood cells, neutrophils, and monocytes, as well as a decrease in lymphocytes. After seven days of treatment, the lymphocyte, monocyte, and neutrophil counts returned to baseline levels in the placebo group; however, in the echinacea group, although the counts for lymphocytes returned to baseline, the monocyte and neutrophil counts continued to remain significantly higher than the baseline values. The treatments were not found to have any significant effects on the distribution of CD3+, CD8+, and CD20+ cells. However, a significant decrease in the population of CD4+ cells on day three and a significant increase in the CD16+ (NK cells) on day eight of treatment in the echinacea group was observed. On day three of the cold, an increase in the oxidative burst capacity of the neutrophils was also observed in both the echinacea and placebo groups. By day eight, however, in the echinacea group, this index of free radical generation had returned to baseline values while in the placebo group an ongoing free radical generation persisted. The difference found between the two groups on day eight was statistically significant (p <0.045). An increase in erythrocytic Cu Zn SOD activity was apparent in both groups on both days three and eight of their colds. Although non-significant, the increase was greater in the echinacea group. Berg et al. conducted a randomized, placebo controlled trial to evaluate the effects of daily oral pretreatment for 28 days with the pressed juice of Echinacea purpurea (Echinacin® EC31) or magnesium supplements on the changes in immunological variables in response to a triathlon sprint (mean duration ± SD: 69.5 ± 10.1 min) 12. Forty-two male triathletes (mean age 27.5 years), undergoing regular training, all with a VO(2max) > 52mL/kg/min, were randomized to one of three treatments. Fluorescence activated flow cytometry analysis of blood cell populations, serum and urine levels of interleukin 6 (IL-6), and soluble interleukin 2 receptor (sIL-2R) together with routine sports laboratory, clinical, chemical, and hematological variables were determined at baseline (day 0), after treatment (day 28), and 1h and 20h after the competition (days 29 and 30). Pretreatment with Echinacin® produced slight changes in total peripheral (CD3+) T-lymphocytes, NK (CD3-CD56+) cells, and CD8+ lymphocyte counts, which remained within the range of baseline variation. In comparison to the placebo group, Echinacin® EC31 markedly decreased sIL-2R in urine before the competition and enhanced the exercise-induced decrease in serum sIL-2R. It further enhanced the exercise-induced increases in urine IL-6 and serum cortisol. None of the Echinacin® EC31-treated athletes developed upper respiratory infections, which were reported by 3/13 and 4/13 subjects treated with magnesium and placebo, respectively. Echinacin® EC31 appears to reduce sIL-2R release, facilitate IL-6 release in response to exercise, and in the present study reduced the documented incidence of respiratory infections, possibly as a result of monocyte/macrophage stimulation.
  • Echinacea, astragalus, and glycyrrhiza herbal tinctures stimulated immune cells as quantified by CD69 expression on CD4 and CD8 T-cells.37 This activation took place within 24 hours of ingestion and continued for at least seven days. In addition, these three herbs had an additive effect on CD69 expression when used in combination.
  • In rats, an increase of primary and secondary antigen-specific IgG production has been seen with continuous echinacea treatment.38
  • Echinacea may invoke an immune response through altered expression of hsp70 and increased WCC.1
  • An herbal combination containing echinacea (Esberitox® N) did not have statistically significant effects on leukocyte counts and other hematological parameters in women receiving post-mastectomy radiation therapy.39 Bendel et al. randomly allocated 50 women receiving post-mastectomy radiation therapy to an herbal combination containing echinacea (Esberitox® N, 50 drops daily throughout the radiation treatment period) or to placebo. Despite the questionable statistical power of the study, the benefit of echinacea is likely to be small at best.
  • In contrast, Sartor found a substantial effect of Esberitox® on radiation-induced leukopenia.40 Forty-eight patients undergoing six weeks of radiation therapy were assigned randomly to Esberitox® or no adjuvant treatment. In the Esberitox® group, 46% missed zero days of therapy because of leukocyte counts <3,000/mm3 vs. 18% in the untreated group. Although these proportions were not statistically compared, they are highly suggestive. The mean number of missed treatment days did not differ significantly, although these results are not interpretable due to an inadequate t-test. In a case series, Pohl found a statistically significant increase in leukocyte counts in 55 patients undergoing radiation therapy after treatment with Esberitox® (at various doses and routes of administration).41 This observational study is suggestive mechanistically but has limited clinical value.
  • Echinacea purpurea was found to significantly reduce s-IgA and the secretion rate of s-IgA at the beginning of a mucosal immunity test in humans. Echinacea did not significantly decrease s-IgA or the secretion rate of s-IgA post intervention.16
  • Wound healing effects: In animal studies, Echinacea angustifolia has exhibited anti-inflammator 42 and antihyaluronidase activity, a likely function of its polysaccharide fraction43, which may stimulate wound healing44.


  • Pharmacokinetics (bioavailability): In order to compare the bioavailability of alkamides from liquid and tablet preparations of Echinacea purpurea (Echinaforce) in humans and to study the effects on ex vivo stimulated blood cells, a randomized, single-dose, crossover study with 10 (8 test, 2 placebo) volunteers has been performed.45 They received either 4mL of the standardized Echinacea purpurea (Echinaforce) tincture or 12 Echinacea purpurea (Echinaforce) tablets or placebo. Both doses contained the same amount (0.07mg) of the major alkamides, dodeca-2E,4E,8Z, 10E/Z-tetraenoic acid isobutylamides. Liquid chromatography electrospray ionization ion-trap mass spectrometry was used to determine the content of alkamides in serum. It was found that the arithmetic mean C(max) of dodeca-2E,4E, 8Z,10E/Z-tetraenoic acid isobutylamides absorbed after oral application of the Echinaforce tincture appeared after 30 minutes (0.40ng/mL serum). In comparison, the t(max) of tablets was 45 min with a C(max) of 0.12ng/mL. An ex vivo stimulation of blood by LPS was carried out to measure the influence of E. purpurea on the innate and adaptive immune system. Both Echinacea purpurea preparations led to the same effects on the immune system according to the concentration of pro-inflammatory cytokines TNF-alpha and IL-8. Twenty-three hours after oral application, a significant down-regulation of TNF-alpha and IL-8 in LPS pre-stimulated whole blood was found. However, no significant changes in the concentration of IL-6 were observed. Although a quarter of the dodeca-2E,4E,8Z, 10E/Z-tetraenoic acid isobutylamides was absorbed from the tablets, the study shows that the formulations trigger the same effects on the measured immune parameters.
  • The maximum concentration of dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides, the main alkamides in the roots of Echinacea angustifolia, appeared already after 30 minutes and was 10.88ng/mL for the 2.5mL dose.

  1. Agnew, L. L., Guffogg, S. P., Matthias, A., Lehmann, R. P., Bone, K. M., and Watson, K. Echinacea intake induces an immune response through altered expression of leucocyte hsp70, increased white cell counts and improved erythrocyte antioxidant defences. J Clin Pharm Ther 2005;30(4):363-369. 15985050
  2. Hu, C. and Kitts, D. D. Studies on the antioxidant activity of Echinacea root extract. J Agric Food Chem 2000;48(5):1466-1472. 10820044
  3. Hudec, J., Burdova, M., Kobida, L., Komora, L., Macho, V., Kogan, G., Turianica, I., Kochanova, R., Lozek, O., Haban, M., and Chlebo, P. Antioxidant capacity changes and phenolic profile of Echinacea purpurea, nettle (Urtica dioica L.), and dandelion (Taraxacum officinale) after application of polyamine and phenolic biosynthesis regulators. J Agric Food Chem 7-11-2007;55(14):5689-5696. 17579437
  4. Mishima, S., Saito, K., Maruyama, H., Inoue, M., Yamashita, T., Ishida, T., and Gu, Y. Antioxidant and immuno-enhancing effects of Echinacea purpurea. Biol Pharm Bull 2004;27(7):1004-1009. 15256730
  5. Pellati, F., Benvenuti, S., Magro, L., Melegari, M., and Soragni, F. Analysis of phenolic compounds and radical scavenging activity of Echinacea spp. J Pharm Biomed Anal 5-16-2004;35(2):289-301. 15063463
  6. Sloley, B. D., Urichuk, L. J., Tywin, C., Coutts, R. T., Pang, P. K., and Shan, J. J. Comparison of chemical components and antioxidants capacity of different Echinacea species. J Pharm Pharmacol 2001;53(6):849-857. 11428661
  7. Voaden, D. J. and Jacobson, M. Tumor inhibitors. 3. Identification and synthesis of an oncolytic hydrocarbon from American coneflower roots. J Med Chem 1972;15(6):619-623. 5030929
  8. Gurley, B. J., Gardner, S. F., Hubbard, M. A., Williams, D. K., Gentry, W. B., Carrier, J., Khan, I. A., Edwards, D. J., and Shah, A. In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle, and saw palmetto. Clin Pharmacol Ther 2004;76(5):428-440. 15536458
  9. Yale, S. H. and Glurich, I. Analysis of the inhibitory potential of Ginkgo biloba, Echinacea purpurea, and Serenoa repens on the metabolic activity of cytochrome P450 3A4, 2D6, and 2C9. J Altern Complement Med 2005;11(3):433-439. 15992226
  10. Goel, V., Lovlin, R., Chang, C., Slama, J. V., Barton, R., Gahler, R., Bauer, R., Goonewardene, L., and Basu, T. K. A proprietary extract from the echinacea plant (Echinacea purpurea) enhances systemic immune response during a common cold. Phytother Res 2005;19(8):689-694. 16177972
  11. Bräunig B, Dorn M, Limburg E, and et al. Enhancement of resistance in common cold by Echinacea purpurea radix. Zeitschrift fur Phytotherpie 1992;13:7-13.
  12. Berg A, Northoff H, Konig D, and et al. Influence of Echinacin (EC31) treatment on exercise-induced immune response in athletes. J Clin Res 1998;1:367-380.
  13. Neri, P. G., Stagni, E., Filippello, M., Camillieri, G., Giovannini, A., Leggio, G. M., and Drago, F. Oral Echinacea purpurea extract in low-grade, steroid-dependent, autoimmune idiopathic uveitis: a pilot study. J Ocul Pharmacol Ther 2006;22(6):431-436. 17238809
  14. Coeugniet, E. G. and Elek, E. Immunomodulation with Viscum album and Echinacea purpurea extracts. Onkologie 1987;10(3 Suppl):27-33. 3309759
  15. Gorski, J. C., Huang, S. M., Pinto, A., Hamman, M. A., Hilligoss, J. K., Zaheer, N. A., Desai, M., Miller, M., and Hall, S. D. The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo. Clin Pharmacol Ther 2004;75(1):89-100. 14749695
  16. Hall, H., Fahlman, M. M., and Engels, H. J. Echinacea purpurea and mucosal immunity. Int J Sports Med 2007;28(9):792-797. 17436202
  17. Schwarz, E., Parlesak, A., Henneicke-von Zepelin, H. H., Bode, J. C., and Bode, C. Effect of oral administration of freshly pressed juice of Echinacea purpurea on the number of various subpopulations of B- and T-lymphocytes in healthy volunteers: results of a double-blind, placebo-controlled cross-over study. Phytomedicine 2005;12(9):625-631. 16194048
  18. Woelkart, K., Koidl, C., Grisold, A., Gangemi, J. D., Turner, R. B., Marth, E., and Bauer, R. Bioavailability and pharmacokinetics of alkamides from the roots of Echinacea angustifolia in humans. J Clin Pharmacol 2005;45(6):683-689. 15901750
  19. Steinmuller, C., Roesler, J., Grottrup, E., Franke, G., Wagner, H., and Lohmann-Matthes, M. L. Polysaccharides isolated from plant cell cultures of Echinacea purpurea enhance the resistance of immunosuppressed mice against systemic infections with Candida albicans and Listeria monocytogenes. Int J Immunopharmacol 1993;15(5):605-614. 8375943
  20. Wacker, A. and Hilbig, W. [Virus-inhibition by echinacea purpurea (author's transl)]. Planta Med 1978;33(1):89-102. 204953
  21. Thompson, K. D. Antiviral activity of Viracea against acyclovir susceptible and acyclovir resistant strains of herpes simplex virus. Antiviral Res 1998;39(1):55-61. 9754950
  22. Shah, S. A., Schlesselman, L., Cios, D., Lipeika, J., Patel, A. A., Kluger, J., and White, C. M. Effects of echinacea on electrocardiographic and blood pressure measurements. Am J Health Syst Pharm 8-1-2007;64(15):1615-1618. 17646564
  23. Bauer R and Wagner H. Echinacea species as potential immunostimulatory drugs. In: Wagner H and Farnsworth NR. Economic and Medicinal Plant Research. New York: Academic Press;1991.
  24. Stimpel, M., Proksch, A., Wagner, H., and Lohmann-Matthes, M. L. Macrophage activation and induction of macrophage cytotoxicity by purified polysaccharide fractions from the plant Echinacea purpurea. Infect Immun 1984;46(3):845-849. 6389368
  25. Mose, J. R. [Effect of Echinacin on phagocytosis and natural killer cells]. Med Welt 12-30-1983;34(51-52):1463-1467. 6366434
  26. Burger, R. A., Torres, A. R., Warren, R. P., Caldwell, V. D., and Hughes, B. G. Echinacea-induced cytokine production by human macrophages. Int J Immunopharmacol 1997;19(7):371-379. 9568541
  27. Burger RA, Torres AR, Warren RP, and et al. Echinacea purpurea induced cytokine production in human peripheral blood adherent mononuclear cells (PBAC). J Allergy Clin Immun 1997;99(1, part 2):283.
  28. Luettig, B., Steinmuller, C., Gifford, G. E., Wagner, H., and Lohmann-Matthes, M. L. Macrophage activation by the polysaccharide arabinogalactan isolated from plant cell cultures of Echinacea purpurea. J Natl Cancer Inst 5-3-1989;81(9):669-675. 2785214
  29. Morazzoni, P., Cristoni, A., Di Pierro, F., Avanzini, C., Ravarino, D., Stornello, S., Zucca, M., and Musso, T. In vitro and in vivo immune stimulating effects of a new standardized Echinacea angustifolia root extract (Polinacea). Fitoterapia15949903
  30. Chen, Y., Fu, T., Tao, T., Yang, J., Chang, Y., Wang, M., Kim, L., Qu, L., Cassady, J., Scalzo, R., and Wang, X. Macrophage activating effects of new alkamides from the roots of Echinacea species. J Nat Prod 2005;68(5):773-776. 15921428
  31. Maass, N., Bauer, J., Paulicks, B. R., Bohmer, B. M., and Roth-Maier, D. A. Efficiency of Echinacea purpurea on performance and immune status in pigs. J Anim Physiol Anim Nutr (Berl) 2005;89(7-8):244-252. 15972074
  32. Brousseau, M. and Miller, S. C. Enhancement of natural killer cells and increased survival of aging mice fed daily Echinacea root extract from youth. Biogerontology 2005;6(3):157-163. 16041619
  33. Jurcic K, Melchart D, and Holzmann M. Two proband studies for the stimulation of granulocyte phagocytosis through echinacea extract containing preparations. Z Phytoterapie 1989;10:67-70.
  34. Bany, J., Siwicki, A. K., Zdanowska, D., Sokolnicka, I., Skopinska-Rozewska, E., and Kowalczyk, M. Echinacea purpurea stimulates cellular immunity and anti-bacterial defence independently of the strain of mice. Pol J Vet Sci 2003;6(3 Suppl):3-5. 14509348
  35. See, D. M., Broumand, N., Sahl, L., and Tilles, J. G. In vitro effects of echinacea and ginseng on natural killer and antibody-dependent cell cytotoxicity in healthy subjects and chronic fatigue syndrome or acquired immunodeficiency syndrome patients. Immunopharmacology 1997;35(3):229-235. 9043936
  36. Bodinet C, Willigmann I, and Beuscher N. Host-resistance increasing activity of root extracts from Echinacea species. Planta Med 1993;59 (Suppl):a672-a673.
  37. Brush, J., Mendenhall, E., Guggenheim, A., Chan, T., Connelly, E., Soumyanath, A., Buresh, R., Barrett, R., and Zwickey, H. The effect of Echinacea purpurea, Astragalus membranaceus and Glycyrrhiza glabra on CD69 expression and immune cell activation in humans. Phytother Res 2006;20(8):687-695. 16807880
  38. Rehman, J., Dillow, J. M., Carter, S. M., Chou, J., Le, B., and Maisel, A. S. Increased production of antigen-specific immunoglobulins G and M following in vivo treatment with the medicinal plants Echinacea angustifolia and Hydrastis canadensis. Immunol Lett 6-1-1999;68(2-3):391-395. 10424448
  39. Bendel, R., Bendel, V., Renner, K., and Stolze, K. [Supplementary treatment with Esberitox of female patients undergoing curative adjuvant irradiation following breast cancer]. Strahlenther Onkol 1988;164(5):278-283. 3131904
  40. Sartor, K. J. [Efficacy of Esberitox in the treatment of radiation-induced leukopenia]. Ther Ggw 1972;111(8):1147-1150. 4558285
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  42. Tragni, E., Tubaro, A., Melis, S., and Galli, C. L. Evidence from two classic irritation tests for an anti-inflammatory action of a natural extract, Echinacina B. Food Chem Toxicol 1985;23(2):317-319. 4040084
  43. Tubaro, A., Tragni, E., Del Negro, P., Galli, C. L., and Della, Loggia R. Anti-inflammatory activity of a polysaccharidic fraction of Echinacea angustifolia. J Pharm Pharmacol 1987;39(7):567-569. 2886631
  44. Tunnerhoff FK and Schwabe HK. Studies in human beings and animals on the influence of echinacea extracts on the formation of connective tissue following the implantation of fibrin. Arzneim Forsch 1956;6:330-334.
  45. Woelkart, K., Marth, E., Suter, A., Schoop, R., Raggam, R. B., Koidl, C., Kleinhappl, B., and Bauer, R. Bioavailability and pharmacokinetics of Echinacea purpurea preparations and their interaction with the immune system. Int J Clin Pharmacol Ther 2006;44(9):401-408. 16995328

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