Flos Arnicae, Herbal Medicine Plant

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Definition

Flos Arnicae consists of the dried fl ower heads (capitula) of Arnica montana

L. (Asteraceae) (1–3).

Synonyms

Doronicum arnica Desf., D. montanum Lam. (4). Asteraceae are also

known as Compositae.

Selected vernacular names

Arnica, arnika, arnique, betoine des montagnes, betouana, Bergwohlverleih,

celtic bane, dokhanolfouh, Echtes Wolferlei, estourniga, estrunica,

Fallkraut, Kraftwurz, leopard’s bane, mountain arnica, mountain tobacco,

St Luzianskraut, Stichwurzel, strunica, Verfangkraut, Wohlverleih,

wolf’s bane, Wundkraut (4–9).

Geographical distribution

Indigenous to central Europe. Widely cultivated around the world (1, 4, 7).

Description

A perennial herb, 20–50 cm high. Aerial portion consists of a basal

rosette of entire oblanceolate leaves up to 17 cm long, five to seven

veins, from the centre of which projects an erect, simple, glandular

hairy stem up to 0.6 m high. Stem bears two to four pairs of cauline

leaves, ovate, elliptic-oblong, lanceolate or oblanceolate, with rounded

or rounded-toothed apex and clothed with numerous nonglandular

and glandular hairs, up to 16 cm long and 5 cm wide. Peduncles, one

to three, bearing alternate bracteoles, extending from the uppermost

pair of cauline leaves; glandular–puberulent, each terminating in a

hemispherical or turbinate capitulum bearing orange-yellow flowers,

which are tubular. Fruits, black to brown, five-ribbed, with a bristle

tuft of hairs (5, 8).

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Plant material of interest: dried fl ower heads

General appearance

Capitulum about 20 mm in diameter and 15 mm deep, with a peduncle

2–3 cm long. Involucre with 18–24 elongated lanceolate bracts, 8–10 mm

long with acute apices, arranged in one or two rows, green with yellowishgreen

external hairs visible under a lens. Receptacle, about 6 mm in diameter,

convex, alveolate and covered with hairs; periphery bears about 20

ligulate fl orets 20–30 mm long; disc bears a greater number of tubular

fl orets about 15 mm long. Ovary, 4–8 mm long, crowned by a pappus of

whitish bristles 4–8 mm long. Some brown achenes, crowned or not by a

pappus, may be present (3).

Organoleptic properties

Odour: characteristic aromatic (1, 3, 5); taste: bitter and acrid (1, 5).

Microscopic characteristics

Epidermis of corolla papillose, containing yellow-orange globular masses,

some cells also containing dark brown–black patches of phytomelan;

base of corolla tube of ligulate fl orets with uniseriate covering trichomes

of four to six cells, up to 1 mm in length; bristles of pappus four to six

cells in diameter and barbed by exertion of the pointed cell apices. Cells

of ovary or fruit walls contain abundant black patches of phytomelan.

Corolla and ovary wall with numerous composite glandular trichomes;

ovary wall with numerous appressed twin hairs each composed of two

narrow parallel cells diverging at the tips. Pollen grains spiky, spherical

35–52 μm in diameter, with fi nely granular exine, spines up to 8 μm long,

three pores and furrows (1).

Powdered plant material

Light yellowish-brown to light olive-brown. Epidermis of the involucre

bracts with stomata and trichomes, which are more abundant on the outer

surface. Trichomes include: uniseriate multicellular covering trichomes,

50–500 μm long, particularly abundant on the margins; secretory trichomes

about 300.0 μm long with uni- or biseriate multicellular stalks

and with multicellullar, globular heads, abundant on the outer surface;

similar trichomes, 80.0 μm long, abundant on the inner surface of the

bract. Epidermis of the ligulate corolla consists of lobed or elongated

cells, a few stomata and trichomes of different types: covering trichomes,

with very sharp ends, whose length may exceed 500 μm; secondary trichomes

with multicellular stalks and multicellular globular heads. Ligule

ends in rounded papillose cells. Epidermis of the ovary covered with trichomes:

secondary trichomes with short stalks and multicellular globular

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heads; twinned covering trichomes usually consisting of two longitudinally

united cells, with common punctuated walls, their ends sharp and

sometimes bifi d. Epidermis of the calyx consists of elongated cells bearing

short, unicellular, covering trichomes pointing towards the upper end of

the bristle. Pollen grains, about 30 μm in diameter, rounded, with spiny

exine, and three germinal pores (3).

General identity tests

Macroscopic and microscopic examinations (1, 3–5), and thin-layer chromatography

for phenolic compounds (3).

Purity tests

Microbiological

Tests for specifi c microorganisms and microbial contamination limits are

as described in the WHO guidelines on quality control methods for medicinal

plants (10).

Foreign organic matter

Not more than 5.0% (3).

Total ash

Not more than 10% (3).

Acid-insoluble ash

Not more than 1.2% (11).

Sulfated ash

Not more than 13% (2).

Water-soluble extractive

Not less than 17% (2).

Alcohol-soluble extractive

Not less than 15% using 45% ethanol (1).

Loss on drying

Not more than 10% (3).

Pesticide residues

The recommended maximum limit of aldrin and dieldrin is not more than

0.05 mg/kg (12). For other pesticides, see the European Pharmacopoeia

Flos Arnicae

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 (12) and the WHO guidelines on quality control methods for medicinal

plants (10) and pesticide residues (13).

Heavy metals

For maximum limits and analysis of heavy metals, consult the WHO

guidelines on quality control methods for medicinal plants (10).

Radioactive residues

Where applicable, consult the WHO guidelines on quality control

methods for medicinal plants (10) for the analysis of radioactive isotopes.

Other purity tests

Chemical tests to be established in accordance with national requirements.

Chemical assays

Contains not less than 0.40% of total sesquiterpene lactones calculated as helenalin

tiglate, determined by high-performance liquid chromatography (3).

Major chemical constituents

The major constituents include the essential oil (0.5%), fatty acids (content

not specifi ed), thymol (content not specifi ed), pseudoguaianolide

sesquiterpene lactones (0.2–0.8%) and fl avonoid glycosides (0.2–0.6%)

(4, 9, 14). The primary sesquiterpene lactones are helenalin, 11α,13-dihydrohelenalin

and their fatty acid esters. Flavonoids include glycosides

and/or glucuronides of spinacetin, hispidulin, patuletin and isorhamnetin,

among others (4, 7, 9, 14–16). The structures of helenalin and 11α,13-

dihydrohelenalin are presented below.

Medicinal uses

Uses supported by clinical data

None.

Pharmacology

Experimental pharmacology

Analgesic and anti-infl ammatory activity

In vitro, helenalin, 5.0 μmol/l, signifi cantly (P < 0.01) suppressed the activity

of prostaglandin synthetase in mouse and rat homogenates, and human

polymorphonuclear neutrophils, indicating an anti-infl ammatory

effect (18). Human polymorphonuclear neutrophil chemotaxis was

inhibited by helenalin, 5.0 μmol/l, in vitro. It was concluded that the

α-methylene-γ-lactone moiety played a role in the anti-infl ammatory

activity of this compound (18). Helenalin, 4.0 μmol/l, selectively inhibited

the transcription factor nuclear factor (NF)-κβ (19).

Intragastric administration of 100.0 mg/kg body weight (bw) of an

80% ethanol extract of Flos Arnicae reduced carrageenan-induced hind

paw oedema by up to 29% in rats (20). Intraperitoneal administration of

2.5–5.0 mg/kg bw of helenalin signifi cantly (P < 0.001) inhibited carrageenan-

induced hind paw oedema in rats by 77% after 72 hours (21). Intraperitoneal

administration of 20.0 mg/kg bw of helenalin strongly inhibited

acetic acid-induced writhing by 93% in mice but did not have

analgesic effects in mice in the hot-plate test. Intraperitoneal administration

of 2.5 mg/kg bw of helenalin to rats inhibited arthritis induced by

Mycobacterium butyricum by 87% (21).

Antioxidant activity

The effect of a tincture of Flos Arnicae on lipid peroxidation and glutathione

metabolism in rat liver was assessed following induction of hepatitis

by the administration of carbon tetrachloride. Intragastric administration

of 0.2 ml/g bw of the tincture to rats decreased the rate of lipid oxidation

and increased the activities of the enzymes involved in glutathione metabolism

(22). Intragastric administration of 0.2 ml/g bw of the tincture

per day for 14 days to rats with hepatitis induced by carbon tetrachloride

led to a normalization of the hydrolytic enzymes (23).

Antitumour activity

Helenalin is cytotoxic to a wide variety of cancer cell lines in vitro, with a

median effective dose (ED50) range of 0.03–1.0 μg/ml (24–27). Intraperi-

Flos Arnicae

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WHO monographs on selected medicinal plants

toneal administration of 1.5–33.3 mg/kg bw of helenalin to mice and rats

had antitumour activity against a variety of chemically induced tumours

(28–30).

Cardiovascular effects

Flos Arnicae and extracts of the fl ower heads have cardiotonic and hypotensive

effects in various animal models. Intravenous administration of a

single dose of 1.0 ml of a tincture of the fl ower heads to rabbits had negative

chronotropic effects and reduced blood pressure (31). Intravenous administration

of 1.0 ml of an aqueous or 95% ethanol extract of the fl ower

heads had cardiotonic effects in frogs, and a tincture demonstrated hypotensive

activity in rabbits after intravenous administration of 1.0 ml (32,

33). A 30% ethanol extract of the fl ower heads, 0.1–0.3% in the bath medium,

had positive inotropic effects in isolated guinea-pig hearts (33).

Intravenous administration of 5.0 g/kg bw of a fl uid extract or tincture of

the fl ower heads increased the blood pressure of cats and guinea-pigs (34).

Helenalin, 50.0 μg/ml, decreased intracellular calcium levels in cultured

fi broblasts, and potentiated the responses induced by vasopressin

and bradykinin (35). Intravenous administration of helenalin had cardiotoxic

effects in mice (25.0 mg/kg bw) and dogs (90.0 mg/kg bw) (36).

Choleretic activity

Intravenous administration of 1.0 ml of a 95% ethanol extract of the fl ower

heads to dogs increased bile secretion by 25–120% (37). Intragastric administration

of a hot aqueous extract of the fl ower heads had choleretic effects

in rats (dose not specifi ed) (38) and dogs (50.0 ml/animal) (39).

Toxicology

The oral median lethal dose (LD50) of a 30% ethanol extract of the fl ower

heads was 37.0 ml/kg in mice (33). The intragastric LD50 for helenalin has

been established for numerous species: mice 150.0 mg/kg bw, rats

125.0 mg/kg bw, rabbits 90.0 mg/kg bw, hamsters 85.0 mg/kg bw and

ewes 125.0 mg/kg bw (40).

Uterine stimulant effects

Intragastric administration of a tincture of the fl ower heads (dose not

specifi ed) had uterine stimulant effects in guinea-pigs (41). Intragastric

administration of a hot aqueous extract of the fl ower heads (dose not

specifi ed) stimulated uterine contractions in rats (38).

Clinical pharmacology

No information available. Clinical trials of homeopathic preparations

were not assessed.

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Adverse reactions

Numerous cases of dermatitis of toxic or allergic origin have been reported

(42), usually following prolonged, external application of a tincture

of Flos Arnicae. The compounds responsible for the hypersensitivity

reaction are the sesquiterpene lactones helenalin and helenalin acetate

(43). Cross-reactivity to other Asteraceae fl owers has been reported (44–47).

The fl ower heads are irritant to the mucous membranes and ingestion

may result in gastroenteritis, muscle paralysis (voluntary and cardiac), an

increase or decrease in pulse rate, heart palpitations, shortness of breath

and death. A fatal case of poisoning following the ingestion of 70.0 g of a

tincture of the fl ower heads has been reported (48).

A case of severe mucosal injuries following the misuse of an undiluted

mouth rinse with a 70% alcohol content, which also contained oil of peppermint

and Flos Arnicae, has been reported (49).

Contraindications

Flos Arnicae is used in traditional systems of medicine as an emmenagogue

(9), and its safety during pregnancy and nursing has not been established.

Therefore, in accordance with standard medical practice, the fl ower

heads should not be administered to pregnant or nursing women. Flos

Arnicae is also contraindicated in cases of known allergy to Arnica or

other members of the Asteraceae (Compositae) (37, 42, 50, 51).

Warnings

A fatal case of poisoning following the ingestion of 70.0 g of a tincture of

Flos Arnicae has been reported (48). Internal use of Flos Arnicae or extracts

of the fl ower heads is not recommended. For external use only. Do

not apply to open or broken skin. Keep out of the reach of children (17).

Precautions

General

Avoid excessive use. Chronic, frequent external applications may induce

allergy-related skin rashes with itching, blister formation, ulcers and superfi

cial necrosis. Prolonged treatment of damaged or injured skin or indolent

leg ulcers may induce the formation of oedematous dermatitis with

the formation of pustules (17).

Carcinogenesis, mutagenesis, impairment of fertility

Helenalin has cytotoxic effects in vitro (see Experimental pharmacology).

However, in the Salmonella/microsome assay, helenalin was not muta-

Flos Arnicae

genic in S. typhimurium strains TA102, TA98 or TA100 at concentrations

of up to 30 μg/ml (52, 53).

Pregnancy: teratogenic effects

Intraperitoneal administration of 6.0–20.0 mg/kg bw of helenalin was not

teratogenic in mice (21).

Pregnancy: non-teratogenic effects

See Contraindications.

Nursing mothers

See Contraindications

.

Paediatric use

See Warnings. For external use only. Do not apply to abraded or broken

skin.

Other precautions

No information available on precautions concerning drug interactions; or

drug and laboratory test interactions.

Dosage forms

Dried fl ower heads and other galenical preparations. Store protected from

light and moisture (7).

Posology

(Unless otherwise indicated)

For external applications only, apply undiluted externally on the affected

area two or three times daily: infusion for compresses, 2 g of Flos Arnicae

per 100 ml water; tincture for compresses, one part Flos Arnicae to 10

parts 70% ethanol; mouth rinse, 10-fold dilution of tincture, do not swallow;

ointment, 20–25% tincture of Flos Arnicae or not more than 15%

essential oil (vehicle not specifi ed) (17).