Ehinacea (Echinacea purpurea L.)

Ehinacea (Echinacea purpurea L.)

Ehinacea (Echinacea purpurea L.)

 

BILJNI PREPARATI EHINACEE:

TINKTURA I MATIČNA TINKTURA 

EHINACEA HSS I TM

 

Echinaceae purpureae radicis recentis extractum ethanolicum liquidum

BILJNI PREPARATI EHINACEE:

TINKTURA I MATIČNA TINKTURA

EHINACEA HSS I TM

 

Echinaceae purpureae radicis recentis extractum ethanolicum liquidum

U PRIPREMI

U skladu sa:

24 November 2014 EMA/HMPC/557979/2013 Committee on Herbal Medicinal Products (HMPC)

Assessment report on Echinacea purpurea (L.) Moench., herba recens

11 March 2010  EMA/HMPC/577786/2008 Committee on Herbal Medicinal Products (HMPC)

Assessment report on Echinacea purpurea (L.) Moench,radix

Pharmacopée française 1989  ECHINACEA POUR PRÉPARATIONS HOMÉOPATHIQUES

 

 

Herba Echinaceae Purpureae

Definition

Herba Echinaceae Purpureae consists of the fresh or dried aerial parts of Echinacea purpurea (L.) Moench harvested in full bloom (Asteraceae) (1).

Synonyms

Brauneria purpurea (L.) Britt., Echinacea intermedia Lindl., E. purpurea (L.) Moench f., E. purpurea (L.) Moench var. arkansanaSteyerm., E. speciosa Paxt., Rudbeckia purpurea L., Rhispida Hoffm., R. serotina Sweet (23).

Asteraceae are also known as Compositae.

Selected vernacular names

Coneflower, purple coneflower herb, purpurfarbener Igelkopf, purpurfarbene Kegelblume, purpurfarbener Sonnenhut, red sunflower, roter Sonnenhut (48).

Description

A hardy, herbaceous perennial. Stems erect, stout, branched, hirsute or glabrous, 60–180 cm high; basal leaves ovate to ovate-lanceolate, acute, coarsely or sharply serrate, petioles up to 25 cm long, blades to 20 cm long and 15cm wide, blade abruptly narrowing to base, often cordate, decurrent on petiole, 3–5 veined; cauline leaves petiolate below, sessile above, 7–20 cm long, 1.5–8cm broad, coarsely serrate to entire, rough to the touch on both surfaces; phyllaries linear-lanceolate, attenuate, entire, pubescent on outer surface, ciliate, passing into the chaff; heads 1.5–3cm long and 5–10mm broad, purplish; pales 9– 13mm long, awn half as long as body; disc corollas 4.5–5.5mm long, lobes 1mm long; achene 4–4.5 mm long, pappus a low crown of equal teeth; pollen grains yellow, 19–21µm in diameter; haploid chromosome number n = 11 (2).

Plant material of interest: fresh or dried aerial parts

General appearance

The macroscopic characteristics of Herba Echinaceae Purpureae are as described above under Description. An abbreviated description is currently unavailable.

Organoleptic properties

Mild, aromatic odour; initially sweet taste that quickly becomes bitter.

Microscopic characteristics

A description of the microscopic characteristics of a cross-section of the aerial parts of the plant is currently unavailable.

Powdered plant material

A description of the powdered plant material is currently unavailable.

Geographical distribution

Echinacea purpurea is native to the Atlantic drainage area of the United States of America and Canada, but not Mexico. Its distribution centres are in Arkansas, Kansas, Missouri, and Oklahoma in the United States of America (2). Echinacea purpureahas been introduced as a cultivated medicinal plant in parts of north and eastern Africa and in Europe (9).

General identity tests

Macroscopic examination (2) and thin-layer chromatography and highperformance liquid chromatography (410–13) of the lipophilic constituents and chicoric acid in methanol extracts.

Purity tests

Microbiology

The test for Salmonella spp. in Herba Echinaceae Purpureae should be negative. The maximum acceptable limits of other microorganisms are as follows (14– 16). For preparation of decoction: aerobic bacteria-not more than 107/g; fungi-not more than 105/g; Escherichia coli-not more than 102/g. Preparations for internal use: aerobic bacteria-not more than 105/g or ml; fungi-not more than 104/g or ml; enterobacteria and certain Gram-negative bacteria-not more than 103/g or ml; Escherichia coli-0/g or ml. Preparations for external use: aerobic bacteria-not more than 102/g or ml; fungi-not more than 102/g or ml; enterobacteria and certain Gram-negative bacteria-not more than 101/g or ml.

Pesticide residues

To be established in accordance with national requirements. Normally, the maximum residue limit of aldrin and dieldrin in Herba Echinaceae Purpureae is not more than 0.05 mg/kg (16). For other pesticides, see WHO guidelines on quality control methods for medicinal plants (14) and guidelines for predicting dietary intake of pesticide residues (17).

Heavy metals

Recommended lead and cadmium levels are no more than 10 and 0.3mg/kg, respectively, in the final dosage form of the plant material (14).

Radioactive residues

For analysis of strontium-90, iodine-131, caesium-134, caesium-137, and plutonium-239, see WHO guidelines on quality control methods for medicinal plants (14).

Other purity tests

Chemical tests and tests for acid-insoluble ash, dilute ethanol-soluble extractive, foreign organic matter, moisture, total ash, and water-soluble extractive to be established in accordance with national requirements.

Chemical assays

For essential oil (0.08–0.32%); chicoric acid (1.2–3.1%) (4). Quantitative analysis of echinacoside, chicoric acid, isobutylamides, and other constituents by high-performance liquid chromatography (4). Quantitative analysis of alkamides and caffeic acid derivatives by thin-layer chromatography and highperformance liquid chromatography (412).

Major chemical constituents

A number of chemical entities have been identified, including alkamides, polyalkenes, polyalkynes, caffeic acid derivatives, and polysaccharides (35–9).

The volatile oil contains, among other compounds, borneol, bornyl acetate, pentadeca-8-(Z)-en-2-one, germacrene D, caryophyllene, and caryophyllene epoxide.

Isobutylamides of C11–C16 straight-chain fatty acids with olefinic or acetylenic bonds (or both) are found in the aerial parts of Herba Echinaceae Purpureae, with the isomeric dodeca-(2E,4E,8Z,10E/Z)-tetraenoic acid isobutylamides.

The caffeic acid ester derivative chicoric acid is the major active compound of this class found in the aerial parts of Echinacea purpurea, with a concentration range of 1.2–3.1%. Chicoric acid methyl ester and other derivatives are also present.

Polysaccharide constituents from Herba Echinaceae Purpureae are of two types: a heteroxylan of average relative molecular mass about 35 000 (e.g. PS-I), and an arabinorhamnogalactan of average relative molecular mass about 45000 (e.g. PS-II).

Other constituents include trace amounts of pyrrolizidine alkaloids (tussilagine (0.006%) and isotussilagine). At these concentrations, the alkaloids are considered to be non-toxic (8). Furthermore, because these alkaloids lack the 1,2-unsaturated necine ring of alkaloids such as senecionine (structure in box) from Senecio species, they are considered to be non-hepatotoxic (3).

Structures of representative constituents are presented below.

Necine ring pyrrolizidine alkaloids:

Dosage forms

Powdered aerial part, pressed juice and galenic preparations thereof for internal and external use (13).

Medicinal uses

Uses supported by clinical data

Herba Echinaceae Purpureae is administered orally in supportive therapy for colds and infections of the respiratory and urinary tract (1357818). Beneficial effects in the treatment of these infections are generally thought to be brought about by stimulation of the immune response (357). External uses include promotion of wound healing and treatment of inflammatory skin conditions (13578919).

Uses described in pharmacopoeias and in traditional systems of medicine

None.

Uses described in folk medicine, not supported by experimental or clinical data

Other medical uses claimed for Herba Echinaceae Purpureae include treatment of yeast infections, side-effects of radiation therapy, rheumatoid arthritis, blood poisoning, and food poisoning (1579).

Pharmacology

Experimental pharmacology

Current claims of the effectiveness of Echinacea purpurea as a stimulator of the immune system are based on numerous scientific studies. The immunostimulant effect is brought about by three mechanisms: activation of phagocytosis and stimulation of fibroblasts; increasing respiratory activity; and increased mobility of the leukocytes (358). Phagocytic activity of standardized extracts of the aerial parts of E. purpurea has been determined. A lyophylisate of the expressed juice of Herba Echinaceae Purpureae significantly increased the percentage of phagocytizing human granulocytes and stimulated the phagocytosis of yeast particles in vitro (2021). Inhibition of hyaluronidase activity, stimulation of the activity of the adrenal cortex, stimulation of the production of properdin (a serum protein which can neutralize bacteria and viruses), and stimulation of interferon production have also been reported after Echinacea treatments (22). The pharmacological activity of Echinacea spp. has been attributed to five component fractions in addition to the essential oil, namely the alkylamides, caffeic acid derivatives, polyalkynes, polyalkenes, and polysaccharides (7). The lipophilic amides, alkamides, and caffeic acid derivatives appear to contribute to the immunostimulant activity of the alcoholic Echinacea extracts by stimulating phagocytosis of polymorphonuclear neutrophil granulocytes (32324). High molecular weight polysaccharides, including heteroxylan, which activates phagocytosis, and arabinogalactan, which promotes the release of tumour necrosis factor and the production of interleukin-1 and interferon beta (1922), have also been implicated in the activity of the aqueous extracts and the powdered drug when taken orally. The overall immunostimulant activity of the alcoholic and aqueous Echinacea extracts appears to depend on the combined effects of several constituents (3523).

Topical applications of Echinacea extracts have been traditionally used to promote wound healing. The first published work on the mechanism of this action was by Büsing (25), who investigated the effect of Echinacea spp. on streptococcal and tissue hyaluronidase. Inhibition of tissue and bacterial hyaluronidase is thought to localize the infection and prevent the spread of causative agents to other parts of the body. In addition to the direct antihyaluronidase activity, an indirect effect on the hyaluronic acid–hyaluronidase system has been reported (26). Stimulation of new tissue production by increasing fibroblast activity, and stimulation of both blood- and tissue-produced phagocytosis, appear to be involved in this mechanism (26). The polysaccharide fraction (echinacin B) appears to promote wound healing by forming a hyaluronic acid–polysaccharide complex that indirectly leads to the inhibition of hyaluronidase (27).

In in vitro experiments, an ethanol extract (65% by volume) of Herba Echinaceae Purpureae inhibited the contraction of collagen by mouse fibroblasts, measured by the collagen lattice diameter (28).

Mouse macrophages pretreated with polysaccharides that were isolated from the supernatant of Herba Echinaceae Purpureae cell culture increased production of tumour necrosis factor alpha, interleukin-1, and interferon beta- 2 and increased cytotoxicity against tumour cells and microorganisms (Leishmania enreittii) (2931).

Purified polysaccharides isolated from large-scale cell cultures of E. purpurea enhanced the spontaneous motility of human polymorphonuclear leukocytes under soft agar and increased the ability of these cells to kill Staphylococcus aureus. Human monocytes were activated to secrete tumour necrosis factor alpha, interleukin-1, and interleukin-6 while the expression of class II human leukocyte antigens was unaffected (32).

For purified caffeic acid derivatives, antiviral activities have been demonstrated (33). Incubation of vesicular stomatitis virus (VSV) with 125µg/ml of chicoric acid for 4 hours reduced the number of viral particles in mouse L-929 murine cells by more than 50% (34).

Clinical pharmacology

Recently 26 controlled clinical trials (18 randomized, 11 double-blind) were systematically reviewed in Germany (24), Nineteen trials studied the prophylaxis or curative treatment of infections, four trials studied the reduction of sideeffects of chemotherapy, and three investigated the modulation of specific immune parameters. The review concluded that Echinacea-containing preparations are efficacious immunomodulators (24). However, it also concluded that there was insufficient evidence for clear therapeutic recommendations as to which preparation or dosage to use for a specific indication (24).

A large-scale longitudinal trial (4598 patients) studied the effects of an ointment containing a lyophylisate of the expressed juice of Herba Echinaceae Purpureae. The ointment was used to treat inflammatory skin conditions, wounds, eczema, burns, herpes simplex, and varicose ulcerations of the legs (19). Therapeutic benefit from the ointment was observed in 85.5% of the cases. The treatment periods ranged from 7.1 to 15.5 days (19).

Contraindications

External use

Allergy to the plant.

Internal use

Should not be used in serious conditions such as tuberculosis, leukosis, collagenosis, multiple sclerosis, AIDS, HIV infection, and autoimmune disorders. Echinacea preparations should not be administered to people with a known allergy to any plant of the Asteraceae (1).

Warnings

No information available.

Precautions

General

Internal or external use should not exceed a period of 8 successive weeks (1).

Carcinogenesis, mutagenesis, impairment of fertility

Mutagenicity and carcinogenicity test results were negative (3535). Doses up to a polysaccharide concentration of 500 mg/ml caused no increase in sister chromatid exchange or structural chromosome aberrations (35).

Pregnancy: teratogenic effects

There are no reliable studies on this subject. Therefore, administration of the drug during pregnancy is not recommended (1).

Nursing mothers

There are no reliable studies on this subject. Nursing mothers should not take the drug without consulting a physician (1).

Paediatric use

Oral administration of Echinacea preparations is not recommended for small children, except on the advice of a physician. Herba Echinaceae Purpureae may be used for external treatment of small superficial wounds.

Other precautions

No information available concerning drug interactions, drug and laboratory test interactions, or non-teratogenic effects on pregnancy.

Adverse reactions

Occasionally allergic reactions may occur owing to allergy to plants in the Asteraceae (Compositae).

Posology

Oral daily dosage of Herba Echinaceae Purpureae, 6–9ml expressed juice (1) for no longer than 8 successive weeks (1). External use of semisolid preparations containing at least 15% pressed juice (1) for no longer than 8 successive weeks (1). Information on dosages for children is not available (7).

References

  1. German Commission E Monograph, Echinaceae purpureae radix. Bundesanzeiger, 1992, 162:29 August.
  2. McGregor RL. The taxonomy of the genus Echinacea (Compositae). University of Kansas science bulletin, 1968, 48:113–142.
  3. Bauer R, Wagner H. Echinacea species as potential immunostimulatory drugs. In: Wagner H, Farnsworth NR, eds. Economic and medicinal plants research. Vol. 5. London, Academic Press, 1991:253–321.
  4. Hänsel R et al., eds. Hagers Handbuch der pharmazeutischen PraxisVol. 6, 5th ed. Berlin, Springer, 1994.
  5. Bisset NG. Max Wichtl’s herbal drugs & phytopharmaceuticals. Boca Raton, FL, CRC Press, 1994.
  6. Farnsworth NR, ed. NAPRALERT database. Chicago, University of Illinois at Chicago, IL, March 15, 1995 production (an on-line database available directly through the University of Illinois at Chicago or through the Scientific and Technical Network (STN) of Chemical Abstracts Services).
  7. Awang DVC, Kindack DG. Herbal medicine, EchinaceaCanadian pharmaceutical journal, 1991, 124:512–516.
  8. Bruneton J. Pharmacognosy, phytochemistry, medicinal plants. Paris, Lavoisier, 1995.
  9. Iwu MM. Handbook of African medicinal plants. Boca Raton, FL, CRC Press, 1993.
  10. Bauer R, Khan IA, Wagner H. Echinacea-Drogen Standardisierung mittels HPLC und DC. Deutsche Apotheker Zeitung, 1986, 126:1065–1070.
  11. Bauer R, Khan IA, Wagner H. Echinacea: Nachweis einer Verfälschung von Echinacea purpurea (l.) Moench. mit Parthenium integrifolium L. Deutsche Apotheker Zeitung, 1987, 127:1325–1330.
  12. Bauer R, Remiger P, Wagner H. Echinacea-Vergleichende DC- und HPLC-Analyse der Herba-drogen von Echinacea purpureaE. pallida und E. angustifolia (3. Mitt.). Deutsche Apotheker Zeitung, 1988, 128:174–180.
  13. Bauer R, Wagner H. Echinacea-Der Sonnenhut-Stand der Forschung. Zeitschrift für Phytotherapie, 1988, 9:151.
  14. Quality control methods for medicinal plant materials. Geneva, World Health Organization, 1998.
  15. Deutsches Arzneibuch 1996. Vol. 2. Methoden der Biologie. Stuttgart, Deutscher Apotheker Verlag, 1996.
  16. European pharmacopoeia, 3rd ed. Strasbourg, Council of Europe, 1997.
  17. Guidelines for predicting dietary intake of pesticide residues, 2nd rev. ed. Geneva, World Health Organization, 1997 (unpublished document WHO/FSF/FOS/97.7; available from Food Safety, WHO, 1211 Geneva 27, Switzerland).
  18. Schöneberger D. The influence of immune-stimulating effects of pressed juice from Echinacea purpurea on the course and severity of colds. Forum immunologie, 1992, 8:2– 12.
  19. Viehmann P. Results of treatment with an Echinacea-based ointment. Erfahrungsheilkunde, 1978, 27:353–358.
  20. Stotzem CD, Hungerland U, Mengs U. Influence of Echinacea purpurea on the phagocytosis of human granulocytes. Medical science research, 1992, 20:719–720.
  21. Bittner E. Die Wirkung von Echinacin auf die Funktion des Retikuloendothelialen Systems [Dissertation]. Freiburg, University of Freiburg, 1969.
  22. Haas H. Arzneipflanzenkunde. Mannheim, BI Wissenschaftsverlag, 1991:134– 135.
  23. Bauer R, Wagner H. Echinacea. Handbuch für Apotheker und andere Naturwissenschaftler. Stuttgart, Wissenschaftliche Verlagsgesellschaft, 1990.
  24. Melchart D et al. Immunomodulation with Echinacea-a systematic review of controlled clinical trials. Phytomedicine, 1994, 1:245–254.
  25. Büsing KH. Hyaluronidase inhibition by Echinacin. ArzneimittelForschung, 1952, 2:467–469.
  26. Koch FE, Haase H. A modification of the spreading test in animal assays. Arzneimittel– Forschung, 1952, 2:464–467.
  27. Bonadeo I, Bottazzi G, Lavazza M. Essenze-Profumi-Piante. OfficinAromi-Saponi- Cosmetici-Aerosol, 1971, 53:281–295.
  28. Zoutewelle G, van Wijk R. Effects of Echinacea purpurea extracts on fibroblast populated collagen lattice contraction.Phytotherapy research, 1990, 4:77–81.
  29. Steinmüller C et al. Polysaccharides isolated from plant cell cultures of Echinacea purpurea enhance the resistance of immunosuppressed mice against systemic infections with Candida albicans and Listeria monocytogenesInternational journal for immunopharmacology, 1993, 15:605–614.
  30. Stempel M et al. Macrophage activation and induction of macrophage cytotoxicity by purified polysaccharide fractions from the plant Echinacea purpurea. Infection and immunity, 1984:845–849.
  31. Luettig B et al. Macrophage activation by polysaccharide arabinogalactan isolated from plant cell cultures of Echinacea purpurea. Journal of the National Cancer Institute, 1989, 81:669–675.
  32. Roesler J et al. Application of purified polysaccharides from cell cultures of the plant Echinacea purpurea to test subjects mediates activation of the phagocyte system. International journal for immunopharmacology, 1991, 13:931–941.
  33. Cheminat A et al. Caffeoyl conjugates from Echinacea species: structures and biological activity. Phytochemistry, 1988, 27:2787–2794.
  34. Müller-Jakic B et al. In vitro inhibition of cyclooxygenase and 5-lipoxygenase by alkamides from Echinacea and Achilleaspecies. Planta medica, 1993:37–42.
  35. Kraus C, Abel G, Schimmer O. Untersuchung einiger Pyrrolizidinalkaloide auf chromosomenschädigende Wirkung in menschlichen Lymphocyten in vitroPlanta medica, 1985, 51:89–91.

 

X X X X X 

Echinacea (Echinacea spp.)

Synonyms / Common Names / Related Terms

Alkamides, American coneflower, Asteraceae (family), black sampson, black susan, cichoric acid and polysaccharides, cock-up-hat, combflower, Echinacea angustifoliaEchinacea 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

Pharmacology:

  • 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 albicansListeria 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 (CD3CD56+) 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.

 

Pharmacodynamics/Kinetics:

  • 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.

 

References

  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 Ther2005;30(4):363-369. 15985050
  2. Hu, C. and Kitts, D. D. Studies on the antioxidant activity of Echinacea root extract. J Agric Food Chem2000;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 Chem7-11-2007;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 Bull2004;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 Anal5-16-2004;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 Pharmacol2001;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 Chem1972;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 Ther2004;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 Med2005;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 Res2005;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 Res1998;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 Ther2006;22(6):431-436. 17238809
  14. Coeugniet, E. G. and Elek, E. Immunomodulation with Viscum album and Echinacea purpurea extracts. Onkologie1987;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 Ther2004;75(1):89-100. 14749695
  16. Hall, H., Fahlman, M. M., and Engels, H. J. Echinacea purpurea and mucosal immunity. Int J Sports Med2007;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. Phytomedicine2005;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 Pharmacol2005;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 Immunopharmacol1993;15(5):605-614. 8375943
  20. Wacker, A. and Hilbig, W. [Virus-inhibition by echinacea purpurea (author’s transl)]. Planta Med1978;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 Res1998;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 Pharm8-1-2007;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 Immun1984;46(3):845-849. 6389368
  25. Mose, J. R. [Effect of Echinacin on phagocytosis and natural killer cells]. Med Welt12-30-1983;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 Immunopharmacol1997;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 Immun1997;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 Inst5-3-1989;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 Prod2005;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. Biogerontology2005;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 Phytoterapie1989;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 Sci2003;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. Immunopharmacology1997;35(3):229-235. 9043936
  36. Bodinet C, Willigmann I, and Beuscher N. Host-resistance increasing activity of root extracts from Echinacea species. Planta Med1993;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 Res2006;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 Lett6-1-1999;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 Onkol1988;164(5):278-283. 3131904
  40. Sartor, K. J. [Efficacy of Esberitox in the treatment of radiation-induced leukopenia]. Ther Ggw1972;111(8):1147-1150. 4558285
  41. Pohl, P. [Treatment of radiation-induced leukopenia with Esberitox]. Ther Ggw1970;109(6):902-906. 5453889
  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 Toxicol1985;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 Pharmacol1987;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 Forsch1956;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 Ther2006;44(9):401-408. 16995328

 

Izvor: www.sigmaaldrich.com

 

 

vrh