acid thymyl ether.1–5 Other constituents
include resins, arnicin (bitter principle), ses-
quiterpene lactones (e.g., helenalin, 11a,13-
dihydrohelenalin, helenalin and 11a,13-dihy-
drohelenalin esters, 2b-ethoxy-6-O-isobutyryl
1-2,3-dihydrohelenalin and 6-O-isobutyrylte-
trahydrohelenalin6–8); tannin, arnisterin (a
sterol), carotenoids (a- andb-carotene, cryp-
toxanthin, lutein, etc.) (KARRER; MERCK);^9
flavonoids (astragalin, betuletol, 6-methoxy-
kaempferol, hispidulin, isoquercetin, jaceosi-
din, pectolinarigenin, etc.),10–12 coumarins
(umbelliferone, scopoletin),^12 and phenolic
acids (p-hydroxybenzoic,p-coumaric, genti-
sic, ferulic, caffeic, vanillic, etc.).^13
Pseudoguaianolides have been reported in
leaves of A. montana, including arnifolin,
arnicolides A, B, C, and D, and loliolide.14,15
PHARMACOLOGY AND BIOLOGICAL
ACTIVITIES
An extract ofArnica montanawas shown to
increase the resistance of animals to bacterial
infections by stimulating phagocytosis of the
bacteria involved, particularlyListeria mono-
cytogenesandSalmonella typhimurium.^16
The sesquiterpene lactones helenalin ace-
tate and 11,13-dihydrohelenalin have shown
platelet aggregation, 5-hydroxytryptamine se-
cretion, and thromboxane formation-inhibit-
ing,^17 and antibacterial and antifungal activi-
tiesin vitro.^18 Numerous esters of helenalin
have shown anti-inflammatory activity in
mice and rats.^19 The anti-inflammatory activ-
ity of A. montanaflowers is attributed to
helenalin,^20 which has the ability to inhibit
proinflammatory gene expression^21 by direct-
ly modifying the transcription factor NF-kB
in vitro.^22 Helenalin has also shownin vitro
antitrypanosomal activity (Trypanosoma
cruziandT. brucei rhodesiense),^23 and anti-
tumor activity against human colorectal cancer
(COLO 320 cells) and human small cell lung
carcinoma (GLC4 cells).^24 It also induces
apoptosis in leukemia (Jurkat T cells).^25
Acidic polysaccharides derived from an
extract ofA. montanahave shown immunos-
timulating activitiesin vitro.^18 Helenalin also
showed immunostimulating activity in a pre-
liminary screening.^26
Double-blind, placebo-controlled clinical
trials of homeopathic preparations ofA. mon-
tanahaveshown questionable or no benefits in
the treatment of postoperative pain,27,28post-
operative bruising,29,30postoperative hemato-
mas,28,31 postoperative swelling,^30 muscle
soreness,32,33post-laser treatment bruising,^29
wound healing, pain, edema, stroke, and
symptoms of acute trauma.^32TOXICOLOGYArnica montanais not recommended for any
internal uses. The plant is an irritant to mucous
membranes, and ingestion may cause burning
pain in the stomach, diarrhea, vomiting, gid-
diness, intense muscular weakness, collapse,
decrease or increase of the pulse rate, short-
ness of breath, and death. One ounce (ca.
30 mL) of the tincture (1 : 0.2 or 20%) has
been reported to produce serious but not fatal
symptoms (USD 23 RD).^34 Evidence suggests
that helenalin is responsible for many, if not
all, of these toxic effects.^34
Reported cases of contact allergic reactions
toA. montanapreparations are numerous and
date from as early as 1844. Cross-reactivity
withotherplantsisalsoreported(e.g.,sunflow-
er, Tagetes, Chrysanthemum).^12 Sesquiter-
pene lactones, especially helenalin and its de-
rivatives, are known sensitizers.6,34–36Data on
the safety of Arnica Montana extract, which is
made from the dried flower heads ofA. mon-
tana,arelacking.IthasanoralLD 50 of>5g/kg
in rats, whereas in mice the LD 50 was 123 mg/
kg p.o. An extract made from the dried plant
showed mutagenic activity in the Ames test, an
effect attributed to the flavonol content.^37USESMedicinal, Pharmaceutical, and Cosmetic.
No longer (or rarely) used in preparations
intended for internal use. Current use is mostlyArnica 43