Arnica is one of the most popular medications in
complementary medicine. This remedy can be ex-
tracted from several plant species belonging to the
Aesteraceae family including Arnica montana,Arnica
chamissonis,Arnica fulgens,Arnica cordifolia and Arnica
sororia, and it is widely sold as tincture, ointment,
cream, gel, and tablet. In 2009, a study showed that
Asteracea-containing remedies were frequently used
in German primary care, and their uses were not asso-
ciated with serious adverse reactions.
8
Arnica can be
used as a homeopathic or herbal remedy. There are
also Arnica-based complex formulations which can
include up to 32 different plant species which share
morphological characteristics and therapeutic proper-
ties to treat inflammation, wounds, hematoma, and
contusion.
9
Among the different varieties, Arnica mon-
tana L. is one of the most used varieties and receives
different local names including leopard’s bane, wolf’s
bane, mountain tobacco, and mountain snuff.
10
This
herb (here referred as Arnica), native of the Siberian
mountains and Central Europe, has been used for the
treatment of numerous pathological conditions,
including pain, stiffness, and swelling associated with
trauma, contusions, sprains, myocarditis, cardiac
insufficiency, arteriosclerosis, angina pectoris, postop-
erative clinical conditions, and for symptomatic relief
in osteoarthritis.
10–12
In traditional medicine, patients
suffering from traumatic disease often use Arnica as an
“alternative”treatment, in the hope of resolving pain
and reducing the use of conventional drugs which
may cause adverse effects. Furthermore, according to
a review concerning the use of alternative and comple-
mentary medicine for rheumatological conditions such
as osteoarthritis, rheumatoid arthritis, and fibromyal-
gia, Arnica was used in 18% of patients attending the
rheumatology department in a Mexican hospital.
13
In
vitro studies have shown that the most active compo-
nents of Arnica, as well as of other members of the
Asteraceae family, are helenalin and other sesquiter-
pene lactones such as 11a,13-dihydrohelenalin and
chamissonolid. Early on, Lyss et al
14
showed that hel-
enalin inhibits the transcriptional factor nuclear factor
kappa B (NF-kB) through the alteration and stabiliza-
tion of the NF-kB/inhibitor of kappa B (IkappaB) com-
plex in T cells, B cells, and epithelial cells and
abrogates kappa B-driven gene expression. This repre-
sents one of the earliest evidences of the anti-
inflammatory properties of Arnica. Later work showed
that helenalin can inhibit human neutrophil migration
and chemotaxis
15
and activities of 5-lipoxygenase and
leukotriene C4 synthase.
16
Helenalin dose-
dependently reduced cell-proliferation in cluster of dif-
ferentiation (CD)4
+
T cells after the activation of the
mitochondrial apoptosis pathway and p53 rapid
stabilization and nuclear localization.
17
Furthermore,
it arrested activated CD4
+
T cell cycle in the G2/M
phase through an increase in p27
KIP1
, p21
WAF1/CIP1
,
and cyclin D2, and a decrease in cyclin B1 and cyclin
A.
17
Helenalin also decreased the expression of cell-
surface receptors CD25, CD28, CD27, and CD120b
which play a key role in NF-kB activation in T cells,
17
supporting the mechanism proposed by Lyss et al in
1997.
14
NF-kB controls the transcription of various
cytokine and adhesion molecule genes in addition to
genes required for antigen presentation.
18
NF-kB acti-
vation is associated with the induction of pain and
inflammation, as observed in animal models of inflam-
matory pain (rat carrageenan pleurisy and mouse car-
rageenan air pouch), characterized by the release of
proinflammatory cytokines (tumor necrosis factor-alpha
[TNF-a] and interleukin-1beta [IL-1b]) and local recruit-
ment of leukocytes.
19
The ability of Arnica to inhibit
activation of transcription factors NF-kBandnuclear
factor of activated T cells and proinflammatory cyto-
kines IL-1band TNF-acorrelate with their quantitative
and qualitative content of sesquiterpene lactones.
20
Additionally, Arnica treatment showed a 4.5-fold inhi-
bition of nitric oxide production, a reduction in the
levels of inducible nitric oxide synthase and
cyclooxygenase-2 protein, a 3-fold reduction in TNF-a
level, and prevented nuclear translocation of NF-kBin
J774 murine macrophage cells challenged with lipopoly-
saccharide.
21
Furthermore, in the rat, 21-day oral treat-
ment with Arnica 30
th
centesimal dilution (30c)
protected against hepatic mitochondrial membrane
FIGURE 1. Mechanisms underlying Arnica effectiveness.
COX-2, cyclooxygenase-2; TNF-a, tumor necrosis factor
alpha; IL-1b, interleukin-1 beta; NO, nitric oxide; iNOS,
inducible nitric oxide synthase; NF-kB, nuclear factor
kappa B; IkB, inhibitor of kappa B.
Effectiveness and Safety of Arnica montana e185
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