WHO monographs on selected medicinal plants

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. arkansana Steyerm., E. speciosa Paxt., Rudbeckia
purpurea L., R. hispida Hoffm., R. serotina Sweet (2, 3).
Asteraceae are also known as Compositae.

Selected vernacular names

Coneflower, purple coneflower herb, purpurfarbener Igelkopf, purpurfarbene
Kegelblume, purpurfarbener Sonnenhut, red sunflower, roter Sonnenhut (4–8).

Description
A hardy, herbaceous perennial. Stems erect, stout, branched, hirsute or gla-
brous, 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 15 cm wide,
blade abruptly narrowing to base, often cordate, decurrent on petiole, 3–5
veined; cauline leaves petiolate below, sessile above, 7–20 cm long, 1.5–8 cm
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 1.5–3 cm long and 5–10 mm broad, purplish; pales 9–
13 mm long, awn half as long as body; disc corollas 4.5–5.5 mm long, lobes
1 mm long; achene 4–4.5 mm long, pappus a low crown of equal teeth; pollen
grains yellow, 19–21 μm 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 de-
scribed above under Description. An abbreviated description is currently
unavailable.

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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
purpurea has 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 high-
performance liquid chromatography (4, 10–13) 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).

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Heavy metals
Recommended lead and cadmium levels are no more than 10 and 0.3 mg/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 extrac-
tive, 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 anal-
ysis 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 high-
performance liquid chromatography (4, 12).

Major chemical constituents

A number of chemical entities have been identified, including alkamides,
polyalkenes, polyalkynes, caffeic acid derivatives, and polysaccharides (3, 5–9).
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 acetyl-
enic 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 45 000
(e.g. PS-II).
Other constituents include trace amounts of pyrrolizidine alkaloids
(tussilagine (0.006%) and isotussilagine). At these concentrations, the alkaloids

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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.

O OH
H
CO2H OH
HO HO 2C
H
OH O

O
chicoric acid

Necine ring pyrrolizidine alkaloids : HO CH 3

O
H3C
O O O O H CH3 O
H CH 3 CH3 O O H
H H H H 1
7 7
7a
1 OH 7a
1 CH 3 7
8
6 2 6 2 6 2
5 N4 3 CH3 5 N
4
3 OH 5 N 3
4

tussilagine isotussilagine senecionine

1,2-saturated 1,2-unsaturated

Dosage forms
Powdered aerial part, pressed juice and galenic preparations thereof for internal
and external use (1, 3).

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 (1, 3, 5, 7, 8, 18).
Beneficial effects in the treatment of these infections are generally thought to be
brought about by stimulation of the immune response (3, 5, 7). External uses
include promotion of wound healing and treatment of inflammatory skin con-
ditions (1, 3, 5, 7, 8, 9, 19).

Uses described in pharmacopoeias and in traditional systems of

medicine
None.

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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 (1, 5, 7, 9).

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 (3, 5, 8). Phagocytic activity of standard-
ized 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 (20, 21). 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 alco-
holic Echinacea extracts by stimulating phagocytosis of polymorphonuclear
neutrophil granulocytes (3, 23, 24). 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 (19, 22), 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 ex-
tracts appears to depend on the combined effects of several constituents (3, 5,
23).
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 hyalu-
ronidase 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 phago-
cytosis, appear to be involved in this mechanism (26). The polysaccharide

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fraction (echinacin B) appears to promote wound healing by forming a hyalu-

ronic 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 (Leishma-
nia enreittii ) (29–31).
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 demon-
strated (33). Incubation of vesicular stomatitis virus ( VSV ) with 125 μg/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 prophy-
laxis or curative treatment of infections, four trials studied the reduction of side-
effects of chemotherapy, and three investigated the modulation of specific
immune parameters. The review concluded that Echinacea-containing prepara-
tions 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, col-
lagenosis, multiple sclerosis, AIDS, HIV infection, and autoimmune disorders.

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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 (3, 5, 35). 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, 6–9 ml 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).

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References
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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 Praxis, Vol. 6, 5th ed.
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DC. Deutsche Apotheker Zeitung, 1986, 126:1065–1070.
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cytosis of human granulocytes. Medical science research, 1992, 20:719–720.
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trolled clinical trials. Phytomedicine, 1994, 1:245–254.

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25. Büsing KH. Hyaluronidase inhibition by Echinacin. Arzneimittel-Forschung, 1952,

2:467–469.
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purpurea enhance the resistance of immunosuppressed mice against systemic infec-
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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
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31. Luettig B et al. Macrophage activation by polysaccharide arabinogalactan isolated
from plant cell cultures of Echinacea purpurea. Journal of the National Cancer Institute,
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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.
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alkamides from Echinacea and Achillea species. Planta medica, 1993:37–42.
35. Kraus C, Abel G, Schimmer O. Untersuchung einiger Pyrrolizidinalkaloide auf
chromosomenschädigende Wirkung in menschlichen Lymphocyten in vitro. Planta
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