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Kriplani Et Al-2017-Journal of Pharmacy and Pharmacology1 PDF
Kriplani Et Al-2017-Journal of Pharmacy and Pharmacology1 PDF
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Keywords Abstract
Arnica montana; anti-inflammatory;
helenalin; sesquiterpene lactones 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,
Correspondence phytochemistry and ethnopharmacology along with special emphasis given on
Priyanka Kriplani, Department of
pharmacological activity of plant A. montana.
Pharmaceutical Sciences, Guru Gobind Singh
College of Pharmacy, Yamunanagar,
Key findings The plant extracts have been reported to possess antibacterial, anti-
135001 Haryana, India. tumor, antioxidant, anti-inflammatory, antifungal and immunomodulatory
E-mail: priyanka15n@gmail.com activity. A wide range of chemical compounds including sesquiterpene lactones
and their short-chain carbonic acid esters, flavonoids, carotenoids, essential oils,
Received January 17, 2017 diterpenes, arnidiol, pyrrolizidine alkaloids, coumarins, phenolic acids, lignans
Accepted March 4, 2017 and oligosaccharides, etc., are found in different parts of the plant.
Summary It has been scrutinized that extensive research has been carried out to
doi: 10.1111/jphp.12724
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.
© 2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 69 (2017), pp. 925–945 925
Arnica montana L. – a plant of healing: review Priyanka Kriplani et al.
Anthemideae Cass. (Achillea ageratum L.)., them and spaced 30 cm apart. Plants may be grown indoor
Astereae Cass. (Conyza bonariensis (L.) Cronquist), by sowing in pots at 13 °C for 1 year and then transplant-
Cardueae Cass. (Centaurea granatensis Boiss. ex DC.)., ing them outdoor after last frost. These are cut before flow-
Cichorieae Lam. & DC. (Andryala integrifolia L., A. ragu- ering to keep stems short and after flowering to produce
sina L., Crepis paludosa (L.) Moench, C. vesicaria L. subsp. secondary bloom.
taraxacifolia (Thuill.) Thell. and Hieracium sp.)., The plant possesses numerous medicinal activity. The
Doroniceae Panero (Doronicum carpetanum Boiss. & Reut. flowers of the plant show greater medicinal value and are
Ex Willk. & Lange, D. grandiflorum Lam. and D. parda- used as antiphlogistic, inotropic, antibiotic, anti-inflamma-
lianches L.)., tory, immunomodulatory, antiplatelet, uterotonic, anti-
Inulaeae Cass. (Chiliadenus glutinosus (L.) Fourr, Dit- rheumatic and analgesic in febrile conditions.[11,59] Both
trichia vis- cosa (L.) Greuter, Inula britannica L., I. hele- oral administration of flowers in the form of fresh plant
nioides DC, I. helvetica mother tincture and local external application in the form
Weber, I. Montana L., I. salicina L., Asteriscus spinosus of cream, ointment or gel or in the form of wet poultice
(L.) Sch. Bip., Pulicaria odora (L.) Rchb., and P. paludosa comprising of a solution that contains one tablespoon of
Link.)., A. montana tincture to a quarter litre of light warm water
Madieae Jeps. (A. montana L.)., have been valued for curing osteoarthritis, alopecia and
Senecioneae Cass. (Senecio doronicum (L.) L., S. jacobaea chronic venous insufficiency.[12] According to European
L., and S. pyrenaicus L.).,[3] and the subgenera are Arctica, pharmacopoeia (1809), A. montana tincture is produced
Andropurpurea, Austromontana, Montana and Chamisso- from A. montana flowers with 0.04% sesquiterpene lac-
nis.[8] The flowers of the plant are traded by the following tones expressed as dihydrohelenalin tiglate. The tincture
pharmaceutical trade names, i.e. Arnica flos (latin), Fleur d contains one part of the drug in 10 parts of ethanol (60%
‘Arnica’ (Fr), Flor de arnica (Sp), Arnikabl€ uten (Ge) and (V/V) to 70% (V/V)). According to European Union, her-
Fiore de Arnica (It), and the trade names for the dried roots bal preparation(s) containing A. montana are tincture
are Arnikawurzel (Ge), Arnicae radix (latin), Raiz de Arnica (1 : 10) extracted with ethanol 70% v/v, tincture (1 : 5)
(Sp) and Racine d ‘Arnique’ (Fr). However, this species is extracted with ethanol 60% v/v and liquid extract (1 : 20)
considered endangered in different European countries like extracted with ethanol 50% m/m, mainly of flowers. Tinc-
Bosnia-Herzegovina, Croatia, Slovenia, Germany and ture is dried by evaporation, and the extract is incorporated
Lithuania, Luxembourg, Sweden, Romania, Balkans, Spain in numerous herbal drug products.[12,13] A. montana has
and Hungary, so in order to protect this species, its cultiva- proved its worth as anti-inflammatory agent. A. montana
tion is increasing but its harvest is not allowed in most extract (3–30%) when blended with one or more therapeu-
European countries including Italy.[9,10] The plant grows tic or pharmaceutical agents, i.e. camphor, menthol,
best at an altitude of 500–2500 m in less fertile meadows eucalyptus oil, mint oil, guaifenesin, topical analgesics,
and on acidic soils in alpine meadows and peat bogs health- non-steroidal anti-inflammatory drugs or either transder-
lands. A. montana L. (Asteraceae) is an herbaceous, peren- mal opioid analgesics in a petroleum base or pluronic
nial, 1–2 ft tall plant, with dark green basal, lower cauline lecithin organogel, reduces inflammation.[14] Alam[15]
leaves (obovate or elliptical to oblanceolate), hairy stems reported that post-traumatic bruising of skin or post-
and bright yellow daisy-like ray flowers. The ray flowers’ surgery, postlaser treatment effects can be prevented by
teeth size is as <1 mm long or between 1 and 2 mm long. applying ointment containing A. montana (30–40%) in a
The second flowers’ diameter varies between 4.9 and petrolatum base to the affected area of the skin.
5.7 cm. The flowers appear in July and August with 1–7 In Videki et al., US patent No. 5043153, compositions
flower heads.[9] The best harvesting time for the flowers are prepared for the treatment of parodonthopathy and in
including the calyx in the Northern Hemisphere is June– Marissal et al., US patent No. 4684522, a cosmetic formula-
August; however, in central Otago, New Zealand, it is tion possessing anticellulitis and slandering activity com-
December–January and for the roots, it is in spring (April) prising of required content of extracts of various plants
and autumn (October). The fresh flowers are used to pre- such as Hedera haelix L., A. montana L. (containing gly-
pare tincture, or they may be dried before in warm shady cols), Aesculus hipocastanus L., Ruscus aculeatus L., extract
area with proper air circulation to prepare tincture. Its fruit containing saponins and kola nut extract containing caf-
is like a seed with white or pale tan bristles and has a pap- feine has been reported.[16]
pus of plumose. Seeds are of cylindrical shape. Plants are In another study, by Ayache et al., US patent No.
germinated by division from cuttings in the spring or by 4795638 revealed a cosmetic preparation for reducing or
A. montana seed; however, seed germination is below 80% eliminating cellulite or fat build-up containing an oily base,
and may take about a month or as long as 2 years to germi- a rubefacient (extracts of capsicum; nicotinic acid salts like
nate. Seeds are sown in the late summer by lightly covering triethanolamine nicotinate; nicotinic acid esters like
926 © 2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 69 (2017), pp. 925–945
Priyanka Kriplani et al. Arnica montana L. – a plant of healing: review
methyl, ethyl, hexyl, phenyl and benzyl nicitinate and alpha various chemical and pharmacological analyses of the plant
tocopherol nicotinate; nicotinyl alcohol and its organic acid which acts as anti-inflammatory agent, antioxidant,
esters like nicotinate and nicotinyl tartarate), one oil sol- antiphlogistic, immunomodulatory and used to treat vari-
uble plant extract of either climbing ivy, A. montana, mari- ous ailments like osteoarthritis. Cosmetic, pharmaceutical
gold, rosemary, ginseng, sage, ruscus, Saint Johns wort, and nutraceutical utility of A. montana ethanolic seed
ulmaria, algae, a volatile polysiloxane and orthosiphon.[17] extract has been reported in combination with other plant
Paradise L. in US patent No. 5795573 A has concluded that active constituents or either alone. It has also been reported
homoeopathic topical anti-inflammatory preparations con- in literature that decoction, infusion or macerated extracts
taining synergistic combination of extracts from A. mon- of A. montana flowers, leaves or aerial parts of the plant
tana, Rhus toxicodendron and Aesculus hippocastanum and can be used to treat numerous ailments such as bowels
belladonna can be used to treat muscular cramps, soreness ache, cough, contusion, cuts, haematoma, headache and
and pain. In many inflammatory diseases in order to relieve rheumatism.[3]
pain or mask pain caused by kinins and kallakreins, it is As recognized in US Pat. No. 4569839, A. montana also
desirable to promote healing and improve circulation to has soothing and healing properties for the hair and skin.
tissues nerves. US patent No. 5162037 to Whitson-Fisch- As taught in US Pat. No. 3832343 by Majoie et al., perhaps
man discloses a homoeopathic mixture to treat pathogenic the most common topical use for A. montana is in the
conditions of body containing one herb or herbal extract of treatment of haematomas as it prevents coagulation of
A. montana, Rhus Toxicum, pineal gland and a magnetically blood. In US patent No. 4938960 to Ismail, extract of
permeable substance.[18] Arnica in combination with Ruta A. montana promotes blood circulation and is therefore
graveolens, Aconitum napellus, Bellis perennis, Hamamelis used for treatment and protection of the skin on the theory
virginiana, Hypericum perforatum, Calendula officinalis, that the A. montana will increase the action of the vitamin
Ledum palustre, Bryonia alba is effective for treating E in the composition.[25]
inflammation.[19]
Recently, Bilia has reported that both the tincture and
Phytochemistry
the dried extract of the plant are physically incompatible
and unstable when formulated as semisolid formulations as One hundred and fifty therapeutically active substances are
well as contain very less content of sesquiterpene lactones. present in A. montana plant, i.e. sesquiterpene lactones, i.e.
Therefore, he introduced a pioneering supercritical carbon helenalin,11a,13-dihydohelenalin and their short-chain car-
dioxide extract, analysed by both HPLC and NMR spec- bonic acid esters (0.3–1% of dry weight in the flower heads,
troscopy containing 9.5%(w/w) of sesquiterpenes. It can be 0.1–0.5% in leaves), flavonoids (0.6–1.7%) by micellar elec-
a good substitute for the topical semisolid preparations trokinetic capillary chromatography[26] in the form of fla-
available in the market.[20] Roots of A. montana contain vonoid glycosides, flavonoid glucuronides and flavonoid
thymol, which is used for flavouring purposes, as antioxi- aglycones; essential oils, composed thoroughly of fatty
dant in foodstuffs and beverages and also as fungicide, acids, thymol derivatives, monoterpenes and sesquiterpene.
preservative and insecticidal agent.[21,22] Roots of the plant Other constituents of A. montana are carotenoids; diterpe-
are also used as bacteriostatic, antiphlogistic, choleretic and nes; arnidiol (a triterpene); pyrrolizidine alkaloids (tussi-
cholagogic due to presence of polyacetylenic compounds, lagine and isotussilagine)[27]; polyacetylenes; coumarins
phenol esters and phenolcarboxylic acids.[23] Alcoholic or (umbelliferone and scopoletin); phenolic acids (chlorogenic
isopropanolic extract of A. montana flowers in the form of acid, caffeic acid and cynarin, 1.0–2.2%)[26]; lignans; dicaf-
liquid formulations such as syrups, tinctures and ointments feoyl quinic derivatives (1,3- 3,5 and 4,5 dicaffeoyl quinic
is used for the treatment of cattle, sheep, horses, swine and acids); and oligosaccharides.[22] It contains sesquiterpene
goats for inflammation of udder, joints, tendons, skin; lactones being metacryl, isobutyryl, tygloyl, methacryloyl,
eczema and to cure wounds of mucous membrane and isovaleryl helenalin derivatives,[28] apigenin, luteolin, hispi-
skin.[23] A. montana in combination with Echinacea angus- dulin, quercetin and kaempferol glycosides in high quanti-
tifolia, Eupatorium perfoliatum and Baptisia tinctoria is used ties. Phytochemical study of A. montana notifies that the
to treat upper respiratory infections.[24] Numerous nature and amount of phytochemicals such as caffeic acid
homoeopathic preparations of the plant are available in the derivatives, phenolics and helenalin esters and dihydrohele-
market such as Hyland’s Arnicated hair oil, shampoo, nalin esters present in the flower heads vary according to
Arnica ointment, Arnica tablets and pellets [69, 129, 309, climatic conditions (i.e. temperature and rainfall) and alti-
30CH, 200CH], Hyland’s Arnica spray as the plant pos- tudinal variations. It has been investigated by many
sesses various activities. Bioactive constituents such as researchers that flowers of the plant are mainly rich in
sesquiterpene lactones, i.e. helenalin an 11a,13-dihydohele- active constituents.[26,29,30] The content and nature of
nalin, phenolic acids and flavonoids, have been isolated by sesquiterpene lactones vary with altitude. The flowers
© 2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 69 (2017), pp. 925–945 927
Arnica montana L. – a plant of healing: review Priyanka Kriplani et al.
CO2H CO2H
OCaf f eoyl OCaf f eoyl
HO HO
OH OH
O O
OH OCaf f eoyl
CO2H
HO OH
OH
O
OH
Chlorogenic acid
928 © 2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 69 (2017), pp. 925–945
Priyanka Kriplani et al. Arnica montana L. – a plant of healing: review
HO O O
O O OH
O
Umbellif erone Scopoletin
Figure 2 Coumarins of Arnica montana plant.[23,33]
O O
OH OMe
N N
H H
2-pyrrolidineacetic acid Methyl ester of 2-pyrrolidineacetic acid
n-Bu n-Bu
OMe OMe
H H
Me OH
O
OMe O
H OMe
OH H
Me
Me
OH
© 2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 69 (2017), pp. 925–945 929
Arnica montana L. – a plant of healing: review Priyanka Kriplani et al.
H3C H3C
H O H O
H3C O OH3C O
O
OR OR
H2C H3C
Helenalin 11a,13 dihydrohelenalin
R
a CH3 CO- acetyl
b CH2=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
H
H3C CH3
H O
H2C
H O
O
HO
CH3
Trans caryophyllene ß-cis-f arnesene 2, 3 -dihydroaromaticin
AcO H H
O O
O O O
HO HO
HO
Germacrene 7-Epi-silphiperf ol-5-ene Chamissonoid Mexicanin 1
930 © 2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 69 (2017), pp. 925–945
Priyanka Kriplani et al. Arnica montana L. – a plant of healing: review
H OH H
OH OH
OH OH OH
HO O HO O HO O HO O
H OH
H OH OH O OH3C OH OH3C OH
OH O OH O OH O
Kaempf erol Quercetin 6-methoxykaempf erol Patuletin
H
H H
OH
OH OH
HO O
HO O HO O
H Oglc
H3CO Oglc H3CO H
OH O OH O
OH O
Kaempf erol 3-O-glucoside 6-methoxy-kaempf erol 3-O-glucoside Hispidulin
OH
OH OH
OH
OH OH
HO O HO O
HO O
investigated for its anti-inflammatory potential on car- that A. montana when administered with herbs like Rue, Wil-
rageenin and rat paw oedema induced by nystatin. Arnica 6c low bark, St. John’s Wort and Comfrey treats by improving
significantly reduced inflammation while in case of his- musculoskeletal healing in case of deep-rooted complaints like
tamine-induced oedema, the action of histamine was inhib- arthritis or mainly in the first 24–48 h of an accident.
ited and the vascular permeability was increased.[42] Research
also investigated that when a solution of A. montana 6cH,
Anti-osteoarthritic activity
dexamethasone or 5% hydroalcoholic solution is injected
into male adult Wistar rats, they show marked anti-inflam- Widrig et al. in 2007 prepared a topical A. montana gel
matory activity. Kawakami et al. in 2011 reported a series of containing helenalin, 11_,13-dihydrohelenalin and its ester
inflammatory-positive cells, which play a major role in that shows significant antiosteoarthritic activity by blocking
inflammatory process, i.e. CD54 (ICAM-1), CD18 (BETA 2 the transcription factor NF-aB and NF-AT. It promotes
integrin), CD45RA (B lymphocytes), CD3 (T lymphocytes), functional capacity of hands and reduces the time period
CD163 (ED2 protein) and MAC 387 (monocytes and macro- and extent of morning stiffness, intensity of pain and the
phages). It was concluded that rats that presented oedema number of painful joints.[44]
after a long time exhibited minor oedema, less degranulation
of mast cells and increase in diameter of lymphatic vessels.[43]
Immunomodulatory activity
In another study, it was concluded that acute non-fibrosed
mastitis can be effectively treated with Arnica 30CH when Polysaccharide fraction of A. montana flowers are reported
taken orally in combination with Healwell VT-6 (comprising to show significant immunostimulating properties (in-
of Calcarea fluorica 200CH, Conium 30CH, Silicea 30CH, Phy- crease of phagocytosis by granulocytes).[24]
tolacca 200CH, Belladonna 30CH, Ipecacuanha 30CH and Bry- DEAE-Sepharose CL-6B and Sephacryl S-400 column
onia 30CH).[42] It has also been reported by Sandra et al.,[12] chromatographic techniques were used to isolate two
© 2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 69 (2017), pp. 925–945 931
Arnica montana L. – a plant of healing: review Priyanka Kriplani et al.
H OH
OH
OH
HO O
HO O
H H
OH O H H
OH O
Apigenin Luteolin
H
OH
OH OH
HO O HO O
OH3C H OH3C H
OH O OH O
CH3 CH3
CH2
CH3
CH3
OH
O
932 © 2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 69 (2017), pp. 925–945
Priyanka Kriplani et al. Arnica montana L. – a plant of healing: review
OH
O I-But
10-isobutyryloxy-8,9-didehydro-thymol Thymol methyl ether
O
O
O
O
OH
O
Zierone (terpenoid) Dimethyl-ionone Pinchotene acetate Isobornyl 2-methyl butanoate Terpineol
H3C CH3
O
O
O
O
O
CH3
O
O
O
O
HO N O
polysaccharides from cell cultures of A. montana, i.e. an factor and possess anticomplementary activity and neutral
acidic arabino-3,6-galactan-protein (mean Mr 100 000), fucogalactoxyloglucan (mean Mr 22 500), which increases
which activates macrophages to release tumour necrosis phagocytosis.[45]
© 2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 69 (2017), pp. 925–945 933
Arnica montana L. – a plant of healing: review Priyanka Kriplani et al.
934 © 2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 69 (2017), pp. 925–945
Priyanka Kriplani et al. Arnica montana L. – a plant of healing: review
© 2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 69 (2017), pp. 925–945 935
Table 1 Clinical Studies of Arnica montana.
936
Study design Duration of Number of subjects by
Authors (years) control type treatment Study and control drugs arms dose; age Diagnosis inclusion criteria Exclusion criteria Efficacy results
Savage et al. Double-blind, placebo- 3 months 1 Arnica 30C, one tablet of medi- 40 patients (20 men and Acute stroke illness Not reported No statistically significant
(1978)[48] controlled cated lactose after every 2 h 20 women) of 77.2– difference in both groups
Placebo: Lactose tablets 80.5 years
Kaziro et al. Double-blind trial, placebo- 8 days after 1 Metronidazole (400 mg tablets) 118 patients Patients with impacted Not reported Metronidazole reduced the pain
(1984)[62] controlled removal of 2 Arnica 200 tablets mandibular wisdom and enhanced the healing
teeth 3 Placebo tablets teeth process after surgery. Arnica
was even less effective than
the placebo
Albertini and Randomized placebo- 1 Arnica 7c and Hypericum 15c 30 patients Dental neuralgic pain after 76% of the patients treated
Goldberg et al. controlled trial 2 Placebo tooth extraction with homoeopathic remedies
(1986)[63] had pain relief vs 40% of
patients receiving placebo
Arnica montana L. – a plant of healing: review
Dorfman et al. Double-blind, placebo- 1 Arnica 5c 39 patients Prolonged venous perfusion Arnica reduced pain,
(1988)[64] controlled clinical study 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. Double-blinded; placebo- 3 weeks 1 Combination ointment: (100 g 159 overall; not reported, Chronic venous No diuretica Changes were in the
(1991)[10] controlled contain: 10 g extract from Arnica how many per group; insufficiency combination treatment, but
flowers with sunflower oil (1 + 5) age not reported differences were not
4000 IU Heparin 5 mg Oil. statistically significant
Chamomillae 5 mg Guajazulen)
2 Mono-ointment: (100 g contains:
10 g extract from Arnica flowers
with sunflower oil (1 + 5))
3 Placebo ointment base
Lokken et al. Double-blind, placebo- 1 Arnica 30D 24 Pain after surgical removal No difference in postsurgical
(1995)[65] controlled crossover trial 2 placebo of bilaterally impacted pain was observed between
mandibular third molars Arnica and placebo.
Postoperative swelling and
bleeding were not
significantly affected by
homoeopathy
Hart et al. Double-blind placebo- 2–3 weeks after 1 Arnica C30 93 women Patients undergoing Patients with previous Arnica in homoeopathy has no
(1997)[66] controlled operation 2 placebo abdominal hysterectomy chronic pain or undergo significant effect on
operations postoperative recovery
Tveiten et al. Randomized double-blind 5 days (1 day 1 Arnica D30 24 in group A (27– Muscle soreness Not reported Arnica D30 has positive effect
(1998)[67] before 2 placebo 54 years) on muscle soreness than
marathon 22 in group in group B placebo but not on cell
running and (31–50 years) damage
3 days after
the run
Priyanka Kriplani et al.
© 2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 69 (2017), pp. 925–945
Table 1 (Continued)
Study design Duration of Number of subjects by
Authors (years) control type treatment Study and control drugs arms dose; age Diagnosis inclusion criteria Exclusion criteria Efficacy results
Ernst et al. Computerized literature NA Pure Arnica formulations NA NA Arnica in combination with Homoeopathic arnica is not
(1998)[58] searches were other herbs efficacious beyond a placebo
performed to retrieve all effect
placebo-controlled
Priyanka Kriplani et al.
© 2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 69 (2017), pp. 925–945
Alonso et al. Double-blinded placebo- 2 weeks, either in 1 Arnica gel (A. montana with 45% 9 pretreatment, 10 post- Facial telangiectases Patients on anticoagulant No statistically significant
(2002)[71] controlled pretreatment alcohol, purified water, with hazel, treatment; dose not therapy difference in both groups
or post- trolamine, carboner, EDTA, specified; age unknown
treatment methyl/propyl paraben)
2 Vehicle
Rosen-zweig et al. Double-blinded placebo- 4 weeks 1 Arnica compress (prepared from 16 Arnica 14 placebo; Acute soft tissue pain (foot/ Not reported No statistically significant
(2002)[10] controlled the whole plant extract, 0.7%) one compress; age ankle, knee, neck/ analgesic benefit compared
2 Placebo compress (contained unknown shoulder) to placebo one hour after
water and food colouring) therapy
Knuesel et al. This open multicentre trial Applied twice 1 Arnica montana fresh plant gel 26 men and 53 women Mild-to-moderate Not reported Arnica gel was found to be
(2002)[72] daily for osteoarthritis (OA) of the effective in treating mild-to-
6 weeks knee moderate osteoarthritis
Jeffrey and Randomized double-blind, 1 Arnica 6D tablets 37 Hand surgery (endoscopic No difference in grip strength or
Belcher placebo-controlled study 2 Arnica Ointment carpal tunnel release) wrist circumference was
(2002)[73] 3 placebo found between Arnica and
placebo. A significant
reduction in pain was
observed in the Arnica-
treated group vs placebo. (P
5 0.03)
Arnica montana L. – a plant of healing: review
937
Table 1 (Continued)
938
Study design Duration of Number of subjects by
Authors (years) control type treatment Study and control drugs arms dose; age Diagnosis inclusion criteria Exclusion criteria Efficacy results
Wolf et al. Prospective, randomized, 1 Arnica 12D 60 Varicose vein surgery Haematoma surface was
(2003)[74] double-blind, placebo- 2 Placebo reduced with Arnica by
controlled pilot trial 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
Arnica montana L. – a plant of healing: review
© 2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 69 (2017), pp. 925–945
Table 1 (Continued)
Study design Duration of Number of subjects by
Authors (years) control type treatment Study and control drugs arms dose; age Diagnosis inclusion criteria Exclusion criteria Efficacy results
Seeley et al. Randomized double-blind 1 Arnica (SinEcch) 29 patients Rhytidectomy Patients receiving Arnica had a
(2006)[77] placebo-controlled study 2 placebo smaller area of ecchymosis
on postoperative days 1, 5, 7
and 10. These differences
Priyanka Kriplani et al.
© 2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 69 (2017), pp. 925–945
Widrig et al. Double-blind Doses of gel Gel preparations 204 patients Osteoarthritis of hands Not reported Preparation of arnica is not
(2007)[44] (4 cm strip), 1 Ibuprofen (5%) inferior to ibuprofen when
gently rubbed 2 Arnica (50 g tincture/100 g, DER treating osteoarthritis of
over the 1 : 20) hands
affected joints
thrice-daily for
3 weeks
Totonchi and Randomized double-blind 1 Arnica 48 patients Rhinoplasty Arnica and dexamethasone
Guyuron et al. clinical study 2 Intravenous dexamethasone plus reduced swelling oedema if
[80]
(2007) oral tapering dose of methylpred- compared with control (P,
nisone or no treatment (control 0.0001). Arnica and control
group) group exhibited more
resolution of ecchymosis if
compared with
dexamethasone
Arnica montana L. – a plant of healing: review
939
Table 1 (Continued)
940
Study design Duration of Number of subjects by
Authors (years) control type treatment Study and control drugs arms dose; age Diagnosis inclusion criteria Exclusion criteria Efficacy results
Paris et al. A phase 3 monocentric 1 Granule composition containing 158 patients Knee ligament Homoeopathic treatment was
(2008)[81] randomized placebo- Arnica 5c, Bryonia alba 5c, Hyper- reconstruction not superior to placebo in
controlled study icum perforatum 5c and Ruta reducing 24-h morphine
graveolens 3D consumption after knee
2 Placebo or no treatment ligament reconstruction.
Nonsignificant difference in
pain assessed by visual
analog scale was observed
between Arnica and placebo
Karow et al. Randomized double-blind, 1 Arnica 4D 88 patients Hallux valgus surgery Arnica and diclofenac had
(2008)[82] parallel-group study 2 Diclofenac sodium equivalent efficacy on wound
irritation, patient mobility
and use of analgesics.
Arnica montana L. – a plant of healing: review
© 2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 69 (2017), pp. 925–945
Table 1 (Continued)
Study design Duration of Number of subjects by
Authors (years) control type treatment Study and control drugs arms dose; age Diagnosis inclusion criteria Exclusion criteria Efficacy results
Kucera et al. Double-blind placebo- 10 days 1 Combination of Arnica tincture 570 patients Acute ankle joint distortion Patients with fractures or On days 3–4, improvement in
(2011)[86] controlled study and HES (spray) complete tears of pain on active motion was
2 Arnica or HES or placebo ligaments, sports significantly higher in the
professionals and Arnica + HES group if
pregnant women compared with the other
Priyanka Kriplani et al.
three groups
Goedemans et al. 12 months 1 Arnica cream 40 patients Pain and bruising following There were no statistical
(2014)[87] 2 mucopolysaccharide polysulfuric postneedling infiltration differences in the effects of
acid arnica and hirudoid on pain
and bruising
Clinical trials.gov Double-blind, placebo- 4 days 1 Arnica montana 28 subjects of 18–89 years Candidates for rhinoplasty Patients who are prisoner,
(2016)[88] controlled 2 Placebo of age surgery at UW pregnant and
Transformations, breastfeeding women,
Ecchymosis 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
© 2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 69 (2017), pp. 925–945
inflammatory
gastrointestinal disease,
oral or contact allergies
to Arnica montana or to
any other member of
the Asteraceae family
Mariani et al. Not reported Aqueous extract Arnica planta tota Rh D3 30 inpatients (age 50–87) Low back pain Patients with other Patients improved during acute
(2009)[89] of Arnica pathologies treatment with no side effect
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 montana L. – a plant of healing: review
941
Arnica montana L. – a plant of healing: review Priyanka Kriplani et al.
Hausen et al. Body lotion containing Skin lesions Allergic contact dermatitis of the NS
(1985)[10] extracts of Arnica face and hands
Leeuw et al. Jogging cream, a Dermatitis
(1987)[10] multicombination with
32 constituents, one of
them Arnica
Delmonte et al. A cream containing 1.5% Enlarging necrotic lesions Sweet’s Syndrome, often
(1998)[10] Arnica of the face and left correlated with leukaemia
leg, together with
malaise and high fever
Knuesel et al. Gel (topical application) Knee osteoarthritis One allergic reaction (not NS
(2002)[90] specified)
Stevinson et al. Tablets (oral treatment) Hand surgery (carpal Dry mouth Arnica 6c (for drowsiness
(2003)[90] tunnel syndrome) Headache and sore tongue)
Feeling ‘throbby’ in head/neck Arnica 30c (for dry
Drowsiness mouth, headache, and
Sore tongue feeling ‘throbby’)
Widrig et al. Gel (topical application) Hand osteoarthritis Skin irritations NS
(2007)[90] Itching
Reddening
Allergic eczema
Increased finger pain
Bronchitis
Chill
Cystitis
Rhinitis
Vertigo
Karow et al. Pills (oral treatment) Hallux valgus surgery Abdominal complaints Arnica 4D
(2008)[90] Racing heart
Cornu et al. (2010)[90] Granules (oral treatment) Aortic valve surgery Cardiovascular events (observed Arnica 5c and Bryonia
in both homoeopathy and alba 5c
placebo groups)
942 © 2017 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 69 (2017), pp. 925–945
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