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Arnica montana L. –a plant of healing: review
Priyanka Kriplani
a,b
, Kumar Guarve
a
and Uttam S. Baghael
c
a
Guru Gobind Singh College of Pharmacy, Yamunanagar, Haryana,
b
I.K. Gujral Punjab Technical University, Jalandhar, Punjab, and
c
Department of
Pharmaceutical Sciences, Khalsa College, Amritsar, Punjab, India
Keywords
Arnica montana; anti-inflammatory;
helenalin; sesquiterpene lactones
Correspondence
Priyanka Kriplani, Department of
Pharmaceutical Sciences, Guru Gobind Singh
College of Pharmacy, Yamunanagar,
135001 Haryana, India.
E-mail: priyanka15n@gmail.com
Received January 17, 2017
Accepted March 4, 2017
doi: 10.1111/jphp.12724
Abstract
Objectives Arnica montana is a widely used therapeutic plant used traditionally
to treat various ailments. The objective of this study was to evaluate the botany,
phytochemistry and ethnopharmacology along with special emphasis given on
pharmacological activity of plant A. montana.
Key findings The plant extracts have been reported to possess antibacterial, anti-
tumor, antioxidant, anti-inflammatory, antifungal and immunomodulatory
activity. A wide range of chemical compounds including sesquiterpene lactones
and their short-chain carbonic acid esters, flavonoids, carotenoids, essential oils,
diterpenes, arnidiol, pyrrolizidine alkaloids, coumarins, phenolic acids, lignans
and oligosaccharides, etc., are found in different parts of the plant.
Summary It has been scrutinized that extensive research has been carried out to
explore the therapeutic potential of flowers of the plant. Therefore, investigations
should be carried out to explore the therapeutic potential of other parts of the
plant for better therapeutic utilization.
Introduction
Asteraceae, also known as the aster, daisy, composite or
sunflower family, is one of the largest flowering plant fam-
ily containing about 1600 genera and more than 23 000
species and 13 subfamilies.
[1–3]
Medicinally important
compounds for curing various ailments are found in some
genera, e.g. species of Arnica, Centaurea granatensis Boiss.,
Conyza bonariensis and Senecio doronicum, which are
reported for the treatment of variety of ailments.
[3]
‘Aster-
aceae’ name is give after one of the genus of this family, i.e.
‘Aster’, which is derived from the Greek word ‘ἀrsήq’
which means star that denotes its inflorescence. Synan-
therology is the name given to the study of this family. As
its petals open in the morning and close in the evening,
members of this family are also called ‘Daisy’, which is
derived from English name: daegesege, which means ‘day’s
eye’.
[4]
The plants of this family grow as annual and peren-
nial herbs and shrubs, vines or trees in forests to high-alti-
tude grasslands.
[5]
Characteristic inflorescences (flowers in
dense heads with involucrum) and the calyx forming a pap-
pus crowning the nut are found in this family.
[6]
A. mon-
tana (Asteraceae) is a high-altitude perennial plant
indigenous to mountain slopes in Europe, northern Asia,
Siberia and America also known as fall-kraut, leopard’s
bane, sneezewort and mountain tobacco
[7]
and had proved
to be an important medicinal plant.
[3]
Occurrence, botanical description and
ethnopharmacology
Arnica montana is used since centuries in homoeopathic
system of medicine. It is used for the treatment of 66 differ-
ent pathological conditions, but frequently used for contu-
sion, wounds, rheumatism and inflammation. In early
medieval texts, the name ‘Arnica’ was not referred any-
where. This name was given in 1533 by the St, Hildegard’s
‘Physica’ editor which was further used in 16th century by
Dalechamps, who thought it was derived from Greek word
‘Ptarmika’ which means something that causes sneezing,
and Haller and Linnaeus were the first people to use the
name ‘Arnica’ in both pharmacy and botany. In northern
Spain, Arnica montana L. was named as: ‘bet
onica de los
montes’, ‘tobaco de montana’, ‘talpa’or‘talpica’, and in
1785, the plant was successfully used in hospitals for the
treatment of loss of vision that occurs without an apparent
lesion affecting the eye also called as amaurosis.
The 32 species known as ‘Arnica’ belong to six botanical
families and five subgenera. Of this, 24 species are Aster-
aceae that belong to eight tribes as follows:
©2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology,69 (2017), pp. 925–945 925
Review
Anthemideae Cass. (Achillea ageratum L.).,
Astereae Cass. (Conyza bonariensis (L.) Cronquist),
Cardueae Cass. (Centaurea granatensis Boiss. ex DC.).,
Cichorieae Lam. &DC. (Andryala integrifolia L., A. ragu-
sina L., Crepis paludosa (L.) Moench, C. vesicaria L. subsp.
taraxacifolia (Thuill.) Thell. and Hieracium sp.).,
Doroniceae Panero (Doronicum carpetanum Boiss. & Reut.
Ex Willk. &Lange, D. grandiflorum Lam. and D. parda-
lianches L.).,
Inulaeae Cass. (Chiliadenus glutinosus (L.) Fourr, Dit-
trichia vis- cosa (L.) Greuter, Inula britannica L., I. hele-
nioides DC, I. helvetica
Weber, I. Montana L., I. salicina L., Asteriscus spinosus
(L.) Sch. Bip., Pulicaria odora (L.) Rchb., and P. paludosa
Link.).,
Madieae Jeps. (A. montana L.).,
Senecioneae Cass. (Senecio doronicum (L.) L., S. jacobaea
L., and S. pyrenaicus L.).,
[3]
and the subgenera are Arctica,
Andropurpurea, Austromontana, Montana and Chamisso-
nis.
[8]
The flowers of the plant are traded by the following
pharmaceutical trade names, i.e. Arnica flos (latin), Fleur d
‘Arnica’ (Fr), Flor de
arnica (Sp), Arnikabl€
uten (Ge) and
Fiore de Arnica (It), and the trade names for the dried roots
are Arnikawurzel (Ge), Arnicae radix (latin), Raiz de Arnica
(Sp) and Racine d ‘Arnique’ (Fr). However, this species is
considered endangered in different European countries like
Bosnia-Herzegovina, Croatia, Slovenia, Germany and
Lithuania, Luxembourg, Sweden, Romania, Balkans, Spain
and Hungary, so in order to protect this species, its cultiva-
tion is increasing but its harvest is not allowed in most
European countries including Italy.
[9,10]
The plant grows
best at an altitude of 500–2500 m in less fertile meadows
and on acidic soils in alpine meadows and peat bogs health-
lands. A. montana L. (Asteraceae) is an herbaceous, peren-
nial, 1–2 ft tall plant, with dark green basal, lower cauline
leaves (obovate or elliptical to oblanceolate), hairy stems
and bright yellow daisy-like ray flowers. The ray flowers’
teeth size is as <1 mm long or between 1 and 2 mm long.
The second flowers’ diameter varies between 4.9 and
5.7 cm. The flowers appear in July and August with 1–7
flower heads.
[9]
The best harvesting time for the flowers
including the calyx in the Northern Hemisphere is June–
August; however, in central Otago, New Zealand, it is
December–January and for the roots, it is in spring (April)
and autumn (October). The fresh flowers are used to pre-
pare tincture, or they may be dried before in warm shady
area with proper air circulation to prepare tincture. Its fruit
is like a seed with white or pale tan bristles and has a pap-
pus of plumose. Seeds are of cylindrical shape. Plants are
germinated by division from cuttings in the spring or by
A. montana seed; however, seed germination is below 80%
and may take about a month or as long as 2 years to germi-
nate. Seeds are sown in the late summer by lightly covering
them and spaced 30 cm apart. Plants may be grown indoor
by sowing in pots at 13 °C for 1 year and then transplant-
ing them outdoor after last frost. These are cut before flow-
ering to keep stems short and after flowering to produce
secondary bloom.
The plant possesses numerous medicinal activity. The
flowers of the plant show greater medicinal value and are
used as antiphlogistic, inotropic, antibiotic, anti-inflamma-
tory, immunomodulatory, antiplatelet, uterotonic, anti-
rheumatic and analgesic in febrile conditions.
[11,59]
Both
oral administration of flowers in the form of fresh plant
mother tincture and local external application in the form
of cream, ointment or gel or in the form of wet poultice
comprising of a solution that contains one tablespoon of
A. montana tincture to a quarter litre of light warm water
have been valued for curing osteoarthritis, alopecia and
chronic venous insufficiency.
[12]
According to European
pharmacopoeia (1809), A. montana tincture is produced
from A. montana flowers with 0.04% sesquiterpene lac-
tones expressed as dihydrohelenalin tiglate. The tincture
contains one part of the drug in 10 parts of ethanol (60%
(V/V) to 70% (V/V)). According to European Union, her-
bal preparation(s) containing A. montana are tincture
(1 : 10) extracted with ethanol 70% v/v, tincture (1 : 5)
extracted with ethanol 60% v/v and liquid extract (1 : 20)
extracted with ethanol 50% m/m, mainly of flowers. Tinc-
ture is dried by evaporation, and the extract is incorporated
in numerous herbal drug products.
[12,13]
A. montana has
proved its worth as anti-inflammatory agent. A. montana
extract (3–30%) when blended with one or more therapeu-
tic or pharmaceutical agents, i.e. camphor, menthol,
eucalyptus oil, mint oil, guaifenesin, topical analgesics,
non-steroidal anti-inflammatory drugs or either transder-
mal opioid analgesics in a petroleum base or pluronic
lecithin organogel, reduces inflammation.
[14]
Alam
[15]
reported that post-traumatic bruising of skin or post-
surgery, postlaser treatment effects can be prevented by
applying ointment containing A. montana (30–40%) in a
petrolatum base to the affected area of the skin.
In Videki et al., US patent No. 5043153, compositions
are prepared for the treatment of parodonthopathy and in
Marissal et al., US patent No. 4684522, a cosmetic formula-
tion possessing anticellulitis and slandering activity com-
prising of required content of extracts of various plants
such as Hedera haelix L.,A. montana L. (containing gly-
cols), Aesculus hipocastanus L., Ruscus aculeatus L., extract
containing saponins and kola nut extract containing caf-
feine has been reported.
[16]
In another study, by Ayache et al., US patent No.
4795638 revealed a cosmetic preparation for reducing or
eliminating cellulite or fat build-up containing an oily base,
a rubefacient (extracts of capsicum; nicotinic acid salts like
triethanolamine nicotinate; nicotinic acid esters like
©2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology,69 (2017), pp. 925–945926
Arnica montana L. –a plant of healing: review Priyanka Kriplani et al.
methyl, ethyl, hexyl, phenyl and benzyl nicitinate and alpha
tocopherol nicotinate; nicotinyl alcohol and its organic acid
esters like nicotinate and nicotinyl tartarate), one oil sol-
uble plant extract of either climbing ivy, A. montana, mari-
gold, rosemary, ginseng, sage, ruscus, Saint Johns wort,
ulmaria, algae, a volatile polysiloxane and orthosiphon.
[17]
Paradise L. in US patent No. 5795573 A has concluded that
homoeopathic topical anti-inflammatory preparations con-
taining synergistic combination of extracts from A. mon-
tana, Rhus toxicodendron and Aesculus hippocastanum and
belladonna can be used to treat muscular cramps, soreness
and pain. In many inflammatory diseases in order to relieve
pain or mask pain caused by kinins and kallakreins, it is
desirable to promote healing and improve circulation to
tissues nerves. US patent No. 5162037 to Whitson-Fisch-
man discloses a homoeopathic mixture to treat pathogenic
conditions of body containing one herb or herbal extract of
A. montana, Rhus Toxicum, pineal gland and a magnetically
permeable substance.
[18]
Arnica in combination with Ruta
graveolens, Aconitum napellus, Bellis perennis, Hamamelis
virginiana, Hypericum perforatum, Calendula officinalis,
Ledum palustre, Bryonia alba is effective for treating
inflammation.
[19]
Recently, Bilia has reported that both the tincture and
the dried extract of the plant are physically incompatible
and unstable when formulated as semisolid formulations as
well as contain very less content of sesquiterpene lactones.
Therefore, he introduced a pioneering supercritical carbon
dioxide extract, analysed by both HPLC and NMR spec-
troscopy containing 9.5%(w/w) of sesquiterpenes. It can be
a good substitute for the topical semisolid preparations
available in the market.
[20]
Roots of A. montana contain
thymol, which is used for flavouring purposes, as antioxi-
dant in foodstuffs and beverages and also as fungicide,
preservative and insecticidal agent.
[21,22]
Roots of the plant
are also used as bacteriostatic, antiphlogistic, choleretic and
cholagogic due to presence of polyacetylenic compounds,
phenol esters and phenolcarboxylic acids.
[23]
Alcoholic or
isopropanolic extract of A. montana flowers in the form of
liquid formulations such as syrups, tinctures and ointments
is used for the treatment of cattle, sheep, horses, swine and
goats for inflammation of udder, joints, tendons, skin;
eczema and to cure wounds of mucous membrane and
skin.
[23]
A. montana in combination with Echinacea angus-
tifolia, Eupatorium perfoliatum and Baptisia tinctoria is used
to treat upper respiratory infections.
[24]
Numerous
homoeopathic preparations of the plant are available in the
market such as Hyland’s Arnicated hair oil, shampoo,
Arnica ointment, Arnica tablets and pellets [69,129,309,
30CH, 200CH], Hyland’s Arnica spray as the plant pos-
sesses various activities. Bioactive constituents such as
sesquiterpene lactones, i.e. helenalin an 11a,13-dihydohele-
nalin, phenolic acids and flavonoids, have been isolated by
various chemical and pharmacological analyses of the plant
which acts as anti-inflammatory agent, antioxidant,
antiphlogistic, immunomodulatory and used to treat vari-
ous ailments like osteoarthritis. Cosmetic, pharmaceutical
and nutraceutical utility of A. montana ethanolic seed
extract has been reported in combination with other plant
active constituents or either alone. It has also been reported
in literature that decoction, infusion or macerated extracts
of A. montana flowers, leaves or aerial parts of the plant
can be used to treat numerous ailments such as bowels
ache, cough, contusion, cuts, haematoma, headache and
rheumatism.
[3]
As recognized in US Pat. No. 4569839, A. montana also
has soothing and healing properties for the hair and skin.
As taught in US Pat. No. 3832343 by Majoie et al., perhaps
the most common topical use for A. montana is in the
treatment of haematomas as it prevents coagulation of
blood. In US patent No. 4938960 to Ismail, extract of
A. montana promotes blood circulation and is therefore
used for treatment and protection of the skin on the theory
that the A. montana will increase the action of the vitamin
E in the composition.
[25]
Phytochemistry
One hundred and fifty therapeutically active substances are
present in A. montana plant, i.e. sesquiterpene lactones, i.e.
helenalin,11a,13-dihydohelenalin and their short-chain car-
bonic acid esters (0.3–1% of dry weight in the flower heads,
0.1–0.5% in leaves), flavonoids (0.6–1.7%) by micellar elec-
trokinetic capillary chromatography
[26]
in the form of fla-
vonoid glycosides, flavonoid glucuronides and flavonoid
aglycones; essential oils, composed thoroughly of fatty
acids, thymol derivatives, monoterpenes and sesquiterpene.
Other constituents of A. montana are carotenoids; diterpe-
nes; arnidiol (a triterpene); pyrrolizidine alkaloids (tussi-
lagine and isotussilagine)
[27]
; polyacetylenes; coumarins
(umbelliferone and scopoletin); phenolic acids (chlorogenic
acid, caffeic acid and cynarin, 1.0–2.2%)
[26]
; lignans; dicaf-
feoyl quinic derivatives (1,3- 3,5 and 4,5 dicaffeoyl quinic
acids); and oligosaccharides.
[22]
It contains sesquiterpene
lactones being metacryl, isobutyryl, tygloyl, methacryloyl,
isovaleryl helenalin derivatives,
[28]
apigenin, luteolin, hispi-
dulin, quercetin and kaempferol glycosides in high quanti-
ties. Phytochemical study of A. montana notifies that the
nature and amount of phytochemicals such as caffeic acid
derivatives, phenolics and helenalin esters and dihydrohele-
nalin esters present in the flower heads vary according to
climatic conditions (i.e. temperature and rainfall) and alti-
tudinal variations. It has been investigated by many
researchers that flowers of the plant are mainly rich in
active constituents.
[26,29,30]
The content and nature of
sesquiterpene lactones vary with altitude. The flowers
©2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology,69 (2017), pp. 925–945 927
Priyanka Kriplani et al. Arnica montana L. –a plant of healing: review
collected from high-altitude healthlands contain principally
helenalin esters while the flowers from lower altitude mead-
ows contain dihydrohelenalin esters in large amount. In
another study, the effect of ecological factors has been
investigated on the content of sesquiterpene lactones in 10
German healthlands. Higher content of sesquiterpene lac-
tones (0.59–1.10%) was found in the flower heads collected
from the foothills of the Alps.
[23]
The phytochemistry of different parts of plant is
discussed below.
Whole plant (Arnicae planta tota)
Various analytical methods such as gas chromatography
with mass selective detection (GC-MSD), spectrophoto-
metric, reverse-phase liquid chromatography (RPLC) and
proton nuclear magnetic resonance spectroscopy
(1HNMR) have been used for analysing the quantity of
lactones present in the plant.
[28,31–33]
Geographical range
has significant effect on the ratios of helenalin and dihy-
drohelenalin esters of A. montana: helenalin esters are
mainly present in central European collections, while
dihydrohelenalin esters are present principally in Spanish
collections. Pulhmann et al. in 1991 has reported that
methylation analysis, partial acidic and enzymatic hydrol-
ysis and 13C NMR spectroscopy have been used for the
identification of two homogeneous polysaccharides from
cell cultures of A. montana, an acidic arabino-3, 6-galac-
tan-protein with mean molecular weight of 100 000 and a
neutral fucogalactoxyloglucan with mean molecular
weight of 22 500 isolated by DEAE-Sepharose CL-6B and
Sephacryl S-400 column chromatography.
[23]
Arnica montana flowers (Arnicae flos)
In 1992, Paßreiter et al. stated that ‘Arnica flower’ consti-
tutes various constituents such as flavonoids (0.4–0.6%),
sesquiterpenes, acetylenes, hydroxycoumarines and phenyl
acrylic acids and essential oil (0.2–0.35% in flower heads
and 0.2–0.5% in leaves), phenolcarbonic acids [such as
chlorogenic acid (5-o-caffeoylquinic acid), cynarin 1,3-di-
O-caffeoylquinic acid, caffeic acid) (Figure 1) by TLC and
HPLC, umbelliferone, scopoletin (Figure 2), 2-pyrrolidi-
neacetic acid and C-1 epimers of the two pyrrolizidine
acids and after Soxhlet extraction by methanol traces of
pyrrolizidine alkaloids (tussilagin and isotussilagin) (Fig-
ure 3) have also been isolated.
[21,27,34]
The flowers of
Arnica species contain especially different sesquiterpene
lactones which have a pseudo-guajonolide structure,
which often may occur as ester derivatives such as 2,3-
dihydroaromaticin, chamissonoid, mexicanin 1 (Fig-
ure 4).
[10]
The total amount of sesquiterpene lactones vary
with maturity of dry flowers; i.e. the amount increases
from 0.5% in buds to 0.9% in withered flowers. Sesquiter-
pene lactones are reported as good anti-inflammatory and
cytotoxic agents.
[23]
Seeds
Dziki in 2009 reported that seeds contain mainly phenolic
acids (chlorogenic, caffeic acid, quercetin and kaempferol)
(Figure 5) and flavonoids (luteolin and apigenin) (Fig-
ure 6), respectively, as active principles.
[35]
Aiello in 2014
reported that the seed yield can be increased with years of
cultivation if regularly fertilizers are added.
[36]
HO
O
OH
OH
OCaf f eoyl
CO
2
H
HO
O
OCaf f e oyl
OH
OCaff eoyl
CO
2
H
1,5 di-o- caffeoylquinic acid 1,4,5-tri-o-caff eoylquinic acid
HO
O
OH
OH
OH
CO
2
H
Chlorogenic acid
Figure 1 Dicaffeoyl quinic derivatives/ phenolic acids of Arnica montana plant.
[23,34]
©2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology,69 (2017), pp. 925–945928
Arnica montana L. –a plant of healing: review Priyanka Kriplani et al.
Roots (Arnicae radix)
Pljevljakusic et al. carried out both quantitative and quali-
tative analyses using GC–FID and GC–MS and concluded
that the main constituents of rhizome and root oils are aro-
matic compounds, i.e. 2,5-dimethoxyp-cymene (28.9–
30.0% and 37.9–40.6%, respectively) (Figure 7), thymol
methyl ether (26.1–27.1% and 9.6–10.6%, respectively)
(Figure 8), pmethoxyheptanophenone (6.1–8.9% and 7.0–
7.5%, respectively) and 2,6-diisopropylanisole (8.9–10.4%
and 12.8–14.1%, respectively) (Figure 9) . The essential
oil from roots and rhizome also contains camphene,
phellandrene, limonene, 5p-mentha-2,4(8)diene, terpineol,
carvacrol, methyl ether, p-diisopropyl-benzene, bornyl
acetate, thymol silphiperfol-5-ene, 7-epi-silphiperfol-5-
ene, silphiperfol-6-ene, modheph-2-ene, isocomene, iso-
bornyl isobutanoate, trans-caryophyllene, 2,5-dimethoxy-
para-cymene, trans-bergamotene, 2,6 diisopropylanisole,
cis-farnesene, germacrene, pinchotene acetate, p-methoxy-
heptanophenone, isobornyl 2-methyl butanoate, isobornyl
OOHO
OO
O
HO
Umbelliferone Scopoletin
Figure 2 Coumarins of Arnica montana plant.
[23,33]
N
H
OH
O
N
H
OMe
O
2-pyrrolidineacetic acid Methyl ester of 2-pyrrolidineacetic aci
d
H
n-Bu
OMe
Me
H
n-Bu
OMe
OH
Tussilagine C-2 epimer isotussilagine
H
O
OMe
Me
OH H
O
OMe
OH
Me
1- epimer of tussilagine 1- epimer of isotussilagine
Figure 3 Pyrrolizidine Alkaloids of Arnica montana plant.
[27]
©2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology,69 (2017), pp. 925–945 929
Priyanka Kriplani et al. Arnica montana L. –a plant of healing: review
isovalerate, sesquiphellandrene, dimethyl-ionone, lignans
and zierone (Figures 4, 7 and 9). Light microscopy, scan-
ning microscopy and transmission microscopy were used
to study the secretory tissues localized as idioblastic secre-
tory cells in the cortical region of the root and rhizome for
essential oil synthesis.
[37]
Petrova reported that the amount
of essential oils varies in different parts of A. montana, from
2.70 to 6.91% in rhizomes and 1.77 to 3.76% in roots. Ken-
nedy in 1998 found that ethanolic extract of roots contains
a panel of non-reducing oligofructosides in later period of
growth and both non-reducing oligofructosides and reduc-
ing inulin-type oligofructosides in early growth period.
[38]
In 2011, Weremczuk-Jezyna et al. separated 56 active
principles from the essential oil of which 10-isobutyryloxy-
8,9-didehydro-thymol isobutyrate and 10-isobutyryloxy-
8,9-didehydro-thymol methyl ether were the main
components obtained by hydrodistillation of hairy roots of
the plant (Shown in Figure 3). He carried out image analy-
sis using LEICA DCML microscope having IM1000 (Imagic
Bildverarbeitung AG Software company, Opfikon, Switzer-
land) software and a digital camera.
[39,58]
Bioactivity
Arnica montana possesses significant anti-inflammatory,
antibacterial, antifungal antioxidant and immunomodula-
tory activity.
Anti-inflammatory activity
Arnica montana has significant anti-inflammatory potential.
Huber et al. in 2011 disclosed that the molecular mechanism
of sesquiterpene lactones differs from that of non-steroidal
anti-inflammatory drugs, i.e. indomethacin and acetyl
salicylic acid. These lactones significantly decrease NFkap-
paB-mediated inflammation as they pass through the skin
easily.
[40]
Phosphorylation and degeneration of IkappaB,
NF-kappaB’s inhibitory subunit, stimulates NF-kappaB.
NFkappaB activation by T cells, B cells and epithelial cells is
inhibited by helenalin which in turn blocks kappaB-driven
gene expression. This blockage is precise and is due to alter-
ation of NF-kappaB/IkappaB complex, inhibiting the dis-
charge of IkappaB by helenalin.
[41]
Arnica 6c has been
O
O
H
3
C
H
H
3
C
OOR H
2
C
O
O
H
3
C
H
H
3
C
OOR H
3
C
Helenalin 11a,13 dihydrohelenalin
R
aCH3CO- acetyl
bCH2=C(CH3)CO- a-methacryl
c CH3CH=C(CH3)CO- tigloyl
d (CH3)2CHCO- isobutyryl
e CH3CH2CH(CH3)CO- 2-methylbutyryl
f (CH3)2CHCH2CO- isovaleryl
CH
3
H
2
CH
CH
3
H
3
C
HO
O
HO
O
H
Trans caryophyllene ß-cis-f arnesene 2, 3 -dihydroaromatici
n
O
O
HO
HO
AcO H
O
O
HO
O
H
Germacrene 7-Epi-silphiperfol-5-ene Chamissonoid Mexicanin 1
Figure 4 Sesquiterpene lactones and its derivatives of Arnica montana plant.
[28,37]
©2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology,69 (2017), pp. 925–945930
Arnica montana L. –a plant of healing: review Priyanka Kriplani et al.
investigated for its anti-inflammatory potential on car-
rageenin and rat paw oedema induced by nystatin. Arnica 6c
significantly reduced inflammation while in case of his-
tamine-induced oedema, the action of histamine was inhib-
ited and the vascular permeability was increased.
[42]
Research
also investigated that when a solution of A. montana 6cH,
dexamethasone or 5% hydroalcoholic solution is injected
into male adult Wistar rats, they show marked anti-inflam-
matory activity. Kawakami et al. in 2011 reported a series of
inflammatory-positive cells, which play a major role in
inflammatory process, i.e. CD54 (ICAM-1), CD18 (BETA 2
integrin), CD45RA (B lymphocytes), CD3 (T lymphocytes),
CD163 (ED2 protein) and MAC 387 (monocytes and macro-
phages). It was concluded that rats that presented oedema
after a long time exhibited minor oedema, less degranulation
of mast cells and increase in diameter of lymphatic vessels.
[43]
In another study, it was concluded that acute non-fibrosed
mastitis can be effectively treated with Arnica 30CH when
taken orally in combination with Healwell VT-6 (comprising
of Calcarea fluorica 200CH, Conium 30CH, Silicea 30CH, Phy-
tolacca 200CH, Belladonna 30CH, Ipecacuanha 30CH and Bry-
onia 30CH).
[42]
It has also been reported by Sandra et al.,
[12]
that A. montana when administered with herbs like Rue, Wil-
low bark, St. John’s Wort and Comfrey treats by improving
musculoskeletal healing in case of deep-rooted complaints like
arthritis or mainly in the first 24–48 h of an accident.
Anti-osteoarthritic activity
Widrig et al. in 2007 prepared a topical A. montana gel
containing helenalin, 11_,13-dihydrohelenalin and its ester
that shows significant antiosteoarthritic activity by blocking
the transcription factor NF-aB and NF-AT. It promotes
functional capacity of hands and reduces the time period
and extent of morning stiffness, intensity of pain and the
number of painful joints.
[44]
Immunomodulatory activity
Polysaccharide fraction of A. montana flowers are reported
to show significant immunostimulating properties (in-
crease of phagocytosis by granulocytes).
[24]
DEAE-Sepharose CL-6B and Sephacryl S-400 column
chromatographic techniques were used to isolate two
OHO
H
OH O
OH
H
OH
OHO
H
OH O
OH
OH
OH
OHO
OH
3
C
OH O
OH
H
OH
OHO
OH
3
C
OH O
OH
OH
OH
OHO
H
OH O
Oglc
H
OH
OHO
H
3
CO
OH O
Oglc
H
OH
OHO
H
3
CO
OH O
H
H
OH
Kaempferol 3-O-glucoside 6-methoxy-kaempferol 3-O-glucoside Hispidulin
OHO
H
OH O
Oglc
OH
OH
OHO
H
3
CO
OH O
Oglc
OH
OH
OHO
H
OH O
Ogla
OH
OH
Quercetin 3-O-glucoside Patuletin 3-O-glucoside Quercetin 3-O-glucuronic acid
Kaempferol Quercetin 6-methoxykaempferol Patuletin
Figure 5 Flavonols of Arnica montana plant.
[26,62]
©2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology,69 (2017), pp. 925–945 931
Priyanka Kriplani et al. Arnica montana L. –a plant of healing: review
OHO
H
OH O
H
H
OH
OHO
H
OH O
H
OH
OH
OHO
OH
3
C
OH O
H
H
OH
OHO
OH
3
C
OH O
H
OH
OH
Apige nin Luteolin
Hispidulin Eupafolin
Figure 6 Flavones of Arnica montana plant.
[62]
CH
3
CH
3
H
3
C
CH
3
CH
3
H
2
C
CH
2
CH
3
CH
3
O
O
OH
Phellandrene Limonene Camphene
2,5-dimethyl-p-cymene Carvacrol ß- Sesquiphellandrene
Figure 7 Terpenes of Arnica montana plant.
[37]
©2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology,69 (2017), pp. 925–945932
Arnica montana L. –a plant of healing: review Priyanka Kriplani et al.
polysaccharides from cell cultures of A. montana, i.e. an
acidic arabino-3,6-galactan-protein (mean Mr 100 000),
which activates macrophages to release tumour necrosis
factor and possess anticomplementary activity and neutral
fucogalactoxyloglucan (mean Mr 22 500), which increases
phagocytosis.
[45]
OH
OI-But
O
10-isobutyryloxy-8,9-didehydro-thymol Thymol methyl ether
Figure 8 Thymol derivatives of Arnica montana plant.
[37]
O
O
O
O
O
OH
Zierone (terpenoid) Dimethyl-ionone Pinchotene acetate Isobornyl 2-methyl butanoate Terpineol
O
O
CH
3
H
3
CCH
3
O
O
O
Isobornyl isovalerate p-mentha-2,4-diene 2,6 diisopropyl anisole Isobornyl isobutanoate
O
O
Bornyl acetate a-isocomene Modeph-2-ene Trans-a-bergamotene
N
O
HO
O
O
Silphiperf ol-6-ene Diisopropyl benzene Pyrrolideneacetic acid p-methoxyheptanophenone
Figure 9 Other phytoconstituents of Arnica montana plant.
[37]
©2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology,69 (2017), pp. 925–945 933
Priyanka Kriplani et al. Arnica montana L. –a plant of healing: review
Antimicrobial activity
Arnica montana extracts also exhibit antimicrobial activ-
ity against Streptococcus sobrinus 6715 and Strep.
Mutans –OMZ 175. Agar diffusion method was used,
and zones of inhibition were measured. Slight inhibition
was observed of the growing cells (19% for Strep.
mutans –OMZ 175 and 15% for Streptococcus sobrinus
6715) and of water-insoluble glucan formation (29%) at
these same concentrations.
[46]
These thymol derivatives present in the roots of A. mon-
tana have been reported to have bactericidal and fungicidal
property whereas the essential oil extracted from the roots
of the plant shows antiphlogistic action.
[21]
Anti-osteoporotic activity (ossification)
US Pat. No. 5478579 by Sawruk taught that A. montana is
a significant source of flavonol aglycone glycoside which
when combined in specific dose with calcium assists in
absorption of calcium through a chelation delivery
system.
[47]
Improves circulation
Arnica montana is reported to relieve symptoms of diseases
relating to the restricted blood flow to nerve endings and
the limbs of patients, and reflex sympathetic dystrophy syn-
drome, which includes fibromyalgia, toxic neuropathy and
diabetic neuropathy.
[18]
Ureotonic activity
The alcoholic extracts of A. montana flower heads or
sesquiterpene lactones isolated from the plant show signifi-
cant uterotonic and contraction-enhancing activity in rab-
bits, rats and cats when injected intravenously (0.3 ml of an
extract).
[21,48]
Increase respiration
Sesquiterpene lactones, i.e. 6-O-acetyl-11,13-dihydrohele-
nalin present in A. montana, are also reported to increases
respiration frequency and volume by 35 and 43%, respec-
tively, in rats and rabbits when injected intravenously,
0.25 mg/kg bw.
[21]
Inotropic activity
Helenalin isolated from A. montana show significant
biphasic positive inotropic effect on the myocardium of
guinea pigs at concentrations of 10
5
–10
3
mol.
[49]
How-
ever, concentrations above 10
3
mol cause an irreversible
negative inotropic action leading to a block of muscle con-
traction.
[21]
Internal use of A. montana at a dose of five drops, three
times a day, improves the mild weakness of heart and ang-
ina pectoris.
[12]
Anxiolytic activity
Ahmed et al. in 2013 evaluated various neuropharmacolog-
ical screening tests like open field activity, stationary rod
activity test and head dip activity of A. montana.
It was observed that the tannins and flavonoids present
in A. montana extract decrease the exploratory activity and
locomotor activity in mice and mice spent more time
in light compartment and therefore had anxiolytic effect.
The development of immobility during forced
swimming test indicated the cessation of affective/motiva-
tional behaviour.
[50]
Antioxidant and protective effect
Arnica montana extract shows significant antioxidant
potential. DPPH (2,20-diphenyl-1-picrylhydrazyl radical)
free radical scavenging method and phosphomolybdate
method have been utilized to determine the antioxidant
potential of the plant. At concentration of 5 mg/ml,
A. montana shows 71.52% DPPH scavenging potential and
63.68% total antioxidant activity (phosphomolybdate
method) which is mainly attributed due to the presence of
flavonoids and phenolic compounds.
[49,51]
Camargo et al. in 2013, evaluated homoeopathic A.
montana’s effect on Ca2
+
and inorganic phosphate-induced
mitochondrial oxidative stress or/and lipid peroxidation
mediated by Fe2
+
citrate by alterations rates of oxygen con-
sumed using mitochondrial suspensions prepared by the
livers of Wistar strain male rats. Arnica 30cH showed
remarkable reduction in mitochondrial O
2
consumption.
Arnica 30cH provides protection against Ca
2+
and inor-
ganic phosphate-induced hepatic mitochondrial membrane
permeability, lipid peroxidation mediated by Fe
2+
citrate
and reactive oxygen-mediated protein fragmentation.
[52]
Hepatoprotective activity
Phenolic compounds isolated from A. montana are used to
revive the bile forming function of liver and improve
the release of chelates and bilirubin and the removal of
cholesterol.
[53]
Marchishin et al. in 1983 have reported that Arnica when
administered to rats with carbon tetrachloride that induced
liver injury increases the synthesis and excretion of bile
acids, bilirubin and cholesterol; bile secretion also acceler-
ates the activity of serum enzymes.
[53]
©2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology,69 (2017), pp. 925–945934
Arnica montana L. –a plant of healing: review Priyanka Kriplani et al.
Insecticidal activity
Arnica montana furnished insecticidal monoterpenoids
which play significant role against store grain pest Tri-
bolium castaneum. Alcoholic dilutions of extracts of drugs
were prepared in various concentrations, increase the per-
centage mortality when used in concentrations, 1–100 mg/
2 ml against store grain pest. In this study, methanol was
used as control and permethrin as standard.
[50]
Hypopigmentation activity
Skin withers with age and also by different environmental
stressors such as solar ultraviolet radiation, which leads to
skin damage such as thickening like plaque, deep furrow-
ing, wrinkle formation, erythema, loss of skin tone and also
hyperpigmentation as a result of increased melanin forma-
tion. AM-2 (helenalin 2-methylbutyrate) or A. montana
extract when used to treat cultured mouse melanoma cells
boosts the HSP70 gene expression with increase in dose
and also activates the transcription factor for hsp genes, i.e.
heat shock factor-1. It is concluded that both A. montana
extract and AM-2 can give good results if incorporated in
hypopigmenting cosmetics.
[54]
Antihair loss activity
Kennedy et al. in 2012 concluded that A. montana (1.6–
2.6% by weight of formulation) in combination with aqua
ammonia in herbal preparations promote hair follicles,
increase hair strength and growth of hair.
[55]
Similarly,
Keeney et al. in 2000 introduced a solution containing aloe
vera gel, A. montana flowers, comfrey leaves, jaborandi
leaves, elkweed, chamomile flowers, colloidal silver solu-
tion, horsetail herbal extract, jojoba, collagen, napca, elas-
tin, saponins and rosemary leaves to be applied topically
for boosting growth of hair.
[51]
Antiplatelet activity
Pawlaczyk et al. in 2009 found that hexuronic acids and
phenolic glycoconjugates present in A. montana are
responsible for the anticoagulant activity of the plant.
[56]
The activity was calculated tests on human plasma such as
prothrombin time and activated partial thromboplastin
time test.
[49]
In 1990, Schroder et al. demonstrated that the
sesquiterpene lactones, i.e. helenalin and 11a-13-dihydro-
helenalin, are mainly responsible for the antiplatelet activ-
ity of the plant using human venous blood for test.
Helenalin contains an a-methylene-r-butyrolactone and an
R-unsaturated cyclopentenone moiety which reacts with
intracellular thiol groups leading to their depletion and
inhibiting aggregatory activity and secretory activity in
platelets. Both compounds interact with platelet sulfhydryl
groups causing inhibition of formation of thromboxane,
secretion of 5-hydroxytryptamine and platelet aggregation
induced by collagen at 3–300 ukl concentration as a result
of decreased phospholipase A2 activity.
[11]
Analgesic
Arnica montana extract is also marked in literature to heal
wounds. In mice, acetic acid-induced writhing test was
used to measure this activity. 0.6% acetic acid per kg was
injected intraperitoneal, and it was concluded that A. mon-
tana, reduces writhes maximally at a dose of 100 mg/kg.
[49]
In another study, it is reported that A. montana alone or
in combination with H.perforatum gel heals surgically
induced incision on the back of Wistar rats effectively.
[57]
Anticough
Arnica 6CH pills showed significant potential against oeso-
phageal reflux which is a very productive cough, hiatus her-
nia. Bruises disappeared immediately, and the cough was
gone too.
[58]
Antihaemorrhagic activity
Stem tincture of A. montana was found to possess anti-
haemorrhagic activity in women of age group 20–35 years,
which reduced postpartum blood loss, which is the signifi-
cant cause of perinatal morbidity and worldwide mortality,
and which occurs in 4% of vaginal deliveries.
[59]
Clinical studies
Many clinical studies have been carried out on A. montana.
Data are given in Table 1.
Toxicological studies
The oral LD50 of an extract was >5 g/kg in rats and
123 mg/kg in mice. The LD50 using intraperitoneal
administration was 31 mg/kg for mice. It has been
reported in literature that Arnica preparations does not
show any signs of contact dermatitis (when used topi-
cally), or any ocular irritation, phototoxicity but shows
mutagenic effects due to flavanols present in the plant.
The Arnica extract increased the numbers of revertants
2–4 times when determined by utilizing S. Typhimurium
TA98 and TA100 in the AMES test. The adverse effects
may occur with a frequency of 1 : 100, and it depends
on the immune system of individual.
[10]
Some of the
laboratory findings of side effects of Arnica preparations
are reported in Table 2.
©2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology,69 (2017), pp. 925–945 935
Priyanka Kriplani et al. Arnica montana L. –a plant of healing: review
Table 1 Clinical Studies of Arnica montana.
Authors (years)
Study design
control type
Duration of
treatment Study and control drugs
Number of subjects by
arms dose; age Diagnosis inclusion criteria Exclusion criteria Efficacy results
Savage et al.
(1978)
[48]
Double-blind, placebo-
controlled
3 months 1Arnica 30C, one tablet of medi-
cated lactose after every 2 h
Placebo: Lactose tablets
40 patients (20 men and
20 women) of 77.2–
80.5 years
Acute stroke illness Not reported No statistically significant
difference in both groups
Kaziro et al.
(1984)
[62]
Double-blind trial, placebo-
controlled
8 days after
removal of
teeth
1Metronidazole (400 mg tablets)
2Arnica 200 tablets
3Placebo tablets
118 patients Patients with impacted
mandibular wisdom
teeth
Not reported Metronidazole reduced the pain
and enhanced the healing
process after surgery. Arnica
was even less effective than
the placebo
Albertini and
Goldberg et al.
(1986)
[63]
Randomized placebo-
controlled trial
1Arnica 7c and Hypericum 15c
2Placebo
30 patients Dental neuralgic pain after
tooth extraction
76% of the patients treated
with homoeopathic remedies
had pain relief vs 40% of
patients receiving placebo
Dorfman et al.
(1988)
[64]
Double-blind, placebo-
controlled clinical study
1Arnica 5c 39 patients Prolonged venous perfusion Arnica reduced pain,
hyperaemia, oedema and
haematoma formation.
Improvement in the blood
flow and slight increase in
coagulation factors and in
platelet aggregation were
observed after Arnica
treatment
Brock et al.
(1991)
[10]
Double-blinded; placebo-
controlled
3 weeks 1Combination ointment: (100 g
contain: 10 g extract from Arnica
flowers with sunflower oil (1 + 5)
4000 IU Heparin 5 mg Oil.
Chamomillae 5 mg Guajazulen)
2Mono-ointment: (100 g contains:
10 g extract from Arnica flowers
with sunflower oil (1 + 5))
3Placebo ointment base
159 overall; not reported,
how many per group;
age not reported
Chronic venous
insufficiency
No diuretica Changes were in the
combination treatment, but
differences were not
statistically significant
Lokken et al.
(1995)
[65]
Double-blind, placebo-
controlled crossover trial
1Arnica 30D
2placebo
24 Pain after surgical removal
of bilaterally impacted
mandibular third molars
No difference in postsurgical
pain was observed between
Arnica and placebo.
Postoperative swelling and
bleeding were not
significantly affected by
homoeopathy
Hart et al.
(1997)
[66]
Double-blind placebo-
controlled
2–3 weeks after
operation
1Arnica C30
2placebo
93 women Patients undergoing
abdominal hysterectomy
Patients with previous
chronic pain or undergo
operations
Arnica in homoeopathy has no
significant effect on
postoperative recovery
Tveiten et al.
(1998)
[67]
Randomized double-blind 5 days (1 day
before
marathon
running and
3 days after
the run
1Arnica D30
2placebo
24 in group A (27–
54 years)
22 in group in group B
(31–50 years)
Muscle soreness Not reported Arnica D30 has positive effect
on muscle soreness than
placebo but not on cell
damage
©2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology,69 (2017), pp. 925–945936
Arnica montana L. –a plant of healing: review Priyanka Kriplani et al.
Table 1 (Continued)
Authors (years)
Study design
control type
Duration of
treatment Study and control drugs
Number of subjects by
arms dose; age Diagnosis inclusion criteria Exclusion criteria Efficacy results
Ernst et al.
(1998)
[58]
Computerized literature
searches were
performed to retrieve all
placebo-controlled
studies on the subject.
The following databases
were searched:
MEDLINE, EMBASE,
CISCOM, and the
Cochrane Library. 89
studies were included
NA Pure Arnica formulations NA NA Arnica in combination with
other herbs
Homoeopathic arnica is not
efficacious beyond a placebo
effect
Andrew et al.
(1998)
[68]
Double-blind placebo-
controlled trial
2 days after run 1A homoeopathic medicine (Arnica
309)
2placebo
519 runners Delayed-onset muscles
soreness after long-
distance races
Not reported Homoeopathic Arnica 309is
ineffective for muscle
soreness
Baillargean et al.
(1998)
[70]
Double-blind, double-
period, crossover
randomized
2 weeks 1Arnica montana 5CH
2placebo
18 men of 22–46 years of
age
Healthy subjects Patients having any
coagulation disorder,
chronic disease, smoking
or on any other
medication
Arnica montana has no
significant effect on bleeding
time in minutes, and no
clinical significant difference
on other tests of blood
coagulation was observed
Ramelet et al.
(2000)
[70]
Randomized, prospective,
multicentre double-blind
trial
1Arnica 5c
2placebo
130 Saphenousstripping No significant difference in
postoperative haematomas
was observed between
Arnica and placebo
Brock (2001)
[10]
3 weeks 1100 g Arnica gel (contained 25 g
Arnica tincture)
2placebo
50 per group; 77 woman;
23 men; age in average
59.2
Chronic venous
insufficiency
Not reported Statistically significant
improvement in both groups;
a significant better effect in
the verum group
Alonso et al.
(2002)
[71]
Double-blinded placebo-
controlled
2 weeks, either in
pretreatment
or post-
treatment
1Arnica gel (A. montana with 45%
alcohol, purified water, with hazel,
trolamine, carboner, EDTA,
methyl/propyl paraben)
2Vehicle
9 pretreatment, 10 post-
treatment; dose not
specified; age unknown
Facial telangiectases Patients on anticoagulant
therapy
No statistically significant
difference in both groups
Rosen-zweig et al.
(2002)
[10]
Double-blinded placebo-
controlled
4 weeks 1Arnica compress (prepared from
the whole plant extract, 0.7%)
2Placebo compress (contained
water and food colouring)
16 Arnica 14 placebo;
one compress; age
unknown
Acute soft tissue pain (foot/
ankle, knee, neck/
shoulder)
Not reported No statistically significant
analgesic benefit compared
to placebo one hour after
therapy
Knuesel et al.
(2002)
[72]
This open multicentre trial Applied twice
daily for
6 weeks
1Arnica montana fresh plant gel 26 men and 53 women Mild-to-moderate
osteoarthritis (OA) of the
knee
Not reported Arnica gel was found to be
effective in treating mild-to-
moderate osteoarthritis
Jeffrey and
Belcher
(2002)
[73]
Randomized double-blind,
placebo-controlled study
1Arnica 6D tablets
2Arnica Ointment
3placebo
37 Hand surgery (endoscopic
carpal tunnel release)
No difference in grip strength or
wrist circumference was
found between Arnica and
placebo. A significant
reduction in pain was
observed in the Arnica-
treated group vs placebo. (P
5 0.03)
©2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology,69 (2017), pp. 925–945 937
Priyanka Kriplani et al. Arnica montana L. –a plant of healing: review
Table 1 (Continued)
Authors (years)
Study design
control type
Duration of
treatment Study and control drugs
Number of subjects by
arms dose; age Diagnosis inclusion criteria Exclusion criteria Efficacy results
Wolf et al.
(2003)
[74]
Prospective, randomized,
double-blind, placebo-
controlled pilot trial
1Arnica 12D
2Placebo
60 Varicose vein surgery Haematoma surface was
reduced with Arnica by
75.5% and with placebo by
71.5% (not significant). Pain
score decreased by 1, 6, 2.2
points with Arnica and 0.3,
6, 0.8 points with placebo.
The results of the study
showed a trend towards a
beneficial effect of Arnica
regarding the reduction in
haematoma and pain during
the postoperative course
Stevinson et al.
(2003)
[75]
Double-blind, placebo-
controlled, randomized
trial
21 days 1Three tablets daily of homoeo-
pathic Arnica 30 or 6 °C
or
2Placebo for 7 days before surgery
and 14 days after surgery
64 adults (18–70 years) Adults undergoing elective
surgery for carpal tunnel
syndrome
Patients currently taking
homoeopathic remedies,
reported previous
hypersensitivity to
homoeopathy, were
taking aspirin, or were
unable to complete the
study diary or attend
follow-up appointments
No statistical differences were
found between
homoeopathic arnica over
placebo in reducing
postoperative pain, bruising
and swelling in patients
Totonchi et al.
(2005)
[10]
Double-blinded placebo-
controlled
6 days, resp.
4 days
1Intravenous dexamethasone intra-
operatively, followed by a 6-day
dose of prednisone
2Arnica SinEcch
3none (as control)
48 overall; 11 male; 37
female; age from 15 to
65
Primary rhinoplasty with
osteotomy
Not reported Statistically no significance
between the groups in
ecchymosis; statistically
significance in reducing
oedema in both groups
Oberbaum et al.
(2005)
[59]
Double-blind, placebo-
controlled, randomized,
clinical trial
Before delivery
and 72 h after
delivery
1Arnica montana C6 and Bellis
perennis C6
2Arnica montana C30 and Bellis
perennis
C30,
or
3Double placebo
Women aged 20–35, at
week 37–43 of
pregnancy, after one to
four previous deliveries,
and scheduled for
spontaneous vaginal
delivery of a single fetus
Pregnant women Women with previous
Caesarean section,
antepartum or
postpartum
haemorrhage in previous
pregnancies, and
coagulopathies
Homoeopathic Arnica montana
and Bellis perennis may
reduce postpartum blood
loss, as compared with
placebo
Leivers (2005)
[76]
Double-blind, placebo-
controlled, randomized,
clinical trial
6 weeks 1Arnica gel (20% tincture)
2placebo
89 patients Venous insufficiency Not reported There was improvement in
venous tone and oedema in
patients on Arnica treatment
than on placebo
Leivers (2005)
[76]
Open, multicentre trail 6 weeks 1Arnica gel (20% tincture)
2placebo
79 patients Mild-to-moderate knee
osteoarthritis
Not reported Arnica decreased the pain,
stiffness of knee and was
effective than placebo
©2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology,69 (2017), pp. 925–945938
Arnica montana L. –a plant of healing: review Priyanka Kriplani et al.
Table 1 (Continued)
Authors (years)
Study design
control type
Duration of
treatment Study and control drugs
Number of subjects by
arms dose; age Diagnosis inclusion criteria Exclusion criteria Efficacy results
Seeley et al.
(2006)
[77]
Randomized double-blind
placebo-controlled study
1Arnica (SinEcch)
2placebo
29 patients Rhytidectomy Patients receiving Arnica had a
smaller area of ecchymosis
on postoperative days 1, 5, 7
and 10. These differences
were statistically significant
only on postoperative days 1
(P, 0.005) and 7 (P, 0.001)
Brinkhaus et al.
(2006)
[78]
Three randomised, placebo-
controlled, double-blind,
sequential clinical trials
Patients were
treated and
followed up for
2 (ART), 8
(CLR)or
11 days (ARJ)
Homoeopathic Arnica 309(a
homoeopathic dilution of
1 : 1030) administered orally with
sucrose globules as the carrier
substance
A total of 227 patients
were enrolled patients
of both genders, age 18
–75 years
Patients with knee diseases
necessitating
arthroscopy, artificial
knee joint implantations
or cruciate ligament
reconstructions
Recent traumas, acute knee
inflammation,
autoimmune disease,
tumour diseases, alcohol
abuse, serious systemic
mental or physical
disease, severe allergic
disease, pregnancy,
breastfeeding, regular
analgesic consumption,
drug abuse or
participation in another
clinical trial
Patients receiving homoeopathic
arnica showed a less
postoperative swelling mainly
in CLR trails.
Robertson et al.
(2007)
[79]
Randomised double-blind,
placebo-controlled
2 tablets 6 times
in the first
postoperative
day and then 2
tablets twice a
day for the
next 7 days.
14 days trail
Arnica 30c or identical placebo 190 patients over the age
of 18
Patients under
tonsillectomy
Patients who had
tonsillectomy in
combination with other
surgery (e.g.
uvulopharyngopalato-
plasty
Arnica montana given after
tonsillectomy provides a
small, but statistically
significant, decrease in pain
scores compared to placebo
Widrig et al.
(2007)
[44]
Double-blind Doses of gel
(4 cm strip),
gently rubbed
over the
affected joints
thrice-daily for
3 weeks
Gel preparations
1Ibuprofen (5%)
2Arnica (50 g tincture/100 g, DER
1 : 20)
204 patients Osteoarthritis of hands Not reported Preparation of arnica is not
inferior to ibuprofen when
treating osteoarthritis of
hands
Totonchi and
Guyuron et al.
(2007)
[80]
Randomized double-blind
clinical study
1Arnica
2Intravenous dexamethasone plus
oral tapering dose of methylpred-
nisone or no treatment (control
group)
48 patients Rhinoplasty Arnica and dexamethasone
reduced swelling oedema if
compared with control (P,
0.0001). Arnica and control
group exhibited more
resolution of ecchymosis if
compared with
dexamethasone
©2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology,69 (2017), pp. 925–945 939
Priyanka Kriplani et al. Arnica montana L. –a plant of healing: review
Table 1 (Continued)
Authors (years)
Study design
control type
Duration of
treatment Study and control drugs
Number of subjects by
arms dose; age Diagnosis inclusion criteria Exclusion criteria Efficacy results
Paris et al.
(2008)
[81]
A phase 3 monocentric
randomized placebo-
controlled study
1Granule composition containing
Arnica 5c, Bryonia alba 5c, Hyper-
icum perforatum 5c and Ruta
graveolens 3D
2Placebo or no treatment
158 patients Knee ligament
reconstruction
Homoeopathic treatment was
not superior to placebo in
reducing 24-h morphine
consumption after knee
ligament reconstruction.
Nonsignificant difference in
pain assessed by visual
analog scale was observed
between Arnica and placebo
Karow et al.
(2008)
[82]
Randomized double-blind,
parallel-group study
1Arnica 4D
2Diclofenac sodium
88 patients Hallux valgus surgery Arnica and diclofenac had
equivalent efficacy on wound
irritation, patient mobility
and use of analgesics.
Diclofenac was more
effective in reducing pain if
compared with Arnica
Adkison et al.
(2010)
[83]
Randomized, double-blind,
placebo-controlled trial
1Arnica cream
2placebo
53 patients Leg pain after calf raises Arnica increased pain scores if
compared with placebo. No
difference in muscle
tenderness and ankle motion
was observed
Cornu et al.
(2010)
[84]
Double-blind placebo-
controlled parallel trial
1A combination of Arnica montana
5c and Bryonia alba 5c granules
2Placebo
90 patients Aortic valve surgery No difference between
homoeopathic treatment and
placebo on bleeding, C-
reactive protein, troponin I
and cumulated morphine
was observed
Leu et al.
(2010)
[85]
Randomized, double-blind
placebo-controlled trial
15% vitamin K
21% vitamin K and 0.3% retinol or
35% vitamin K or
420% Arnica or white petrolatum
(placebo)
16 patients 595-nm pulsed-dye laser-
induced bruises on the
bilateral upper inner
arms
The mean improvement in
bruising associated with 20%
Arnica was greater than with
white petrolatum (P5
0.003), and the mixture of
1% vitamin K and 0.3%
retinol (P5 0.01) while
improvement with Arnica
was not greater than with
5% vitamin K cream
Huber et al.
(2011)
[40]
Single-blind, randomized 30 days Combudoron consists of an
ethanolic extract of stinging nettle
(Urtica urens) and Arnica (Arnica
montana). Placebo liquid
consisted of equivalent ethanol
without extract from stinging
nettle and Arnica
Two healthy male subjects
(Caucasian, age 33 and
47 years, body mass
index 24 and 23 kg/m
2
)
Erbium YAG-
Laser-induced burns
Not reported Combudoron seems to have
positive effects on healing of
grade 2 laser-induced burns
©2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology,69 (2017), pp. 925–945940
Arnica montana L. –a plant of healing: review Priyanka Kriplani et al.
Table 1 (Continued)
Authors (years)
Study design
control type
Duration of
treatment Study and control drugs
Number of subjects by
arms dose; age Diagnosis inclusion criteria Exclusion criteria Efficacy results
Kucera et al.
(2011)
[86]
Double-blind placebo-
controlled study
10 days 1Combination of Arnica tincture
and HES (spray)
2Arnica or HES or placebo
570 patients Acute ankle joint distortion Patients with fractures or
complete tears of
ligaments, sports
professionals and
pregnant women
On days 3–4, improvement in
pain on active motion was
significantly higher in the
Arnica +HES group if
compared with the other
three groups
Goedemans et al.
(2014)
[87]
12 months 1Arnica cream
2mucopolysaccharide polysulfuric
acid
40 patients Pain and bruising following
postneedling infiltration
There were no statistical
differences in the effects of
arnica and hirudoid on pain
and bruising
Clinical trials.gov
(2016)
[88]
Double-blind, placebo-
controlled
4 days 1Arnica montana
2Placebo
28 subjects of 18–89 years
of age
Candidates for rhinoplasty
surgery at UW
Transformations,
Ecchymosis
Patients who are prisoner,
pregnant and
breastfeeding women,
taking anticoagulants
(such as blood thinners),
antiplatelet drugs (such
as NSAIDS), oral
corticosteroid or other
homoeopathic remedies
during the peri-operative
period
Patients with a bruising
or bleeding disorder,
severe liver or kidney
disease, malignancy,
infection,
immunodeficiency,
metabolic syndrome,
infectious or
inflammatory
gastrointestinal disease,
oral or contact allergies
to Arnica montana or to
any other member of
the Asteraceae family
Mariani et al.
(2009)
[89]
Not reported Aqueous extract
of Arnica
planta tota Rh
D3,
administered
locally
subcutaneously
once a day for
6 days. 15
patients (group
A) received
further
3 months of
arnica
ampoules
Arnica planta tota Rh D3 30 inpatients (age 50–87) Low back pain Patients with other
pathologies
Patients improved during acute
treatment with no side effect
©2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology,69 (2017), pp. 925–945 941
Priyanka Kriplani et al. Arnica montana L. –a plant of healing: review
Conclusion
In this review, the morphology, distribution, pharmacolog-
ical data and phytochemistry of the medicinal plant,
A. montana, have been studied. The pharmacological and
phytochemical studies of the plant have revealed that the
plant possess numerous activities. Although from time
immemorial, the extracts of the plant have been utilized to
treat various ailments but proper investigation of its
mechanism of action, pharmacotherapeutics, toxicity pro-
file, standardization and clinical studies, modern dosage
forms of various phytoconstituents present in the plant can
be prepared. Till date, significant investigations have been
carried out on exploring the medicinal potential of the
flowers of the plant. So, now there is a need to explore the
medicinal potential of other parts of the plant to produce
economic and therapeutically better products.
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[10]
Body lotion containing
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Priyanka Kriplani et al. Arnica montana L. –a plant of healing: review
