Recent Patents on Anti-Cancer Potential of Helenalin

Author(s): Priyanka Kriplani*, Kumar Guarve

Journal Name: Recent Patents on Anti-Cancer Drug Discovery

Volume 15 , Issue 2 , 2020


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Abstract:

Background: Arnica montana, containing helenalin as its principal active constituent, is the most widely used plant to treat various ailments. Recent studies indicate that Arnica and helenalin provide significant health benefits, including anti-inflammatory, neuroprotective, antioxidant, cholesterol-lowering, immunomodulatory, and most important, anti-cancer properties.

Objective: The objective of the present study is to overview the recent patents of Arnica and its principal constituent helenalin, including new methods of isolation, and their use in the prevention of cancer and other ailments.

Methods: Current prose and patents emphasizing the anti-cancer potential of helenalin and Arnica, incorporated as anti-inflammary agents in anti-cancer preparations, have been identified and reviewed with particular emphasis on their scientific impact and novelty.

Results: Helenalin has shown its anti-cancer potential to treat multiple types of tumors, both in vitro and in vivo. It has also portrayed synergistic effects when given in combination with other anti- cancer drugs or natural compounds. New purification/isolation techniques are also developing with novel helenalin formulations and its synthetic derivatives have been developed to increase its solubility and bioavailability.

Conclusion: The promising anti-cancer potential of helenalin in various preclinical studies may open new avenues for therapeutic interventions in different tumors. Thus clinical trials validating its tumor suppressing and chemopreventive activities, particularly in conjunction with standard therapies, are immediately required.

Keywords: Activities, anti-cancer, Arnica, helenalin, patents, synthetic derivatives.

[1]
Dietz V. Homeopathic and herbal preparations of Arnica montana for treatment of musculoskeletal injuries. Integr Med 1998; 1: 42-4.
[2]
Obón C, Rivera D, Verde A, et al. Arnica: A multivariate analysis of the botany and ethnopharmacology of a medicinal plant complex in the Iberian Peninsula and the Balearic Islands. J Ethnopharmacol 2012; 144(1): 44-56.
[http://dx.doi.org/10.1016/j.jep.2012.08.024] [PMID: 22947388]
[3]
Schrder H, Lasche W, Strobach H, et al. Helenalin and 11 alpha,13-dihydrohelenalin, two constituents from Arnica montana L., inhibit human platelet function via thiol-dependent pathways. Thromb Res 1990; 57(6): 839-45.
[http://dx.doi.org/10.1016/0049-3848(90)90151-2] [PMID: 2116680]
[4]
Oberbaum M, Galoyan N, Lerner-Geva L, et al. The effect of the homeopathic remedies Arnica montana and Bellis perennis on mild postpartum bleeding-a randomized, double-blind, placebo -controlled study-preliminary results. Complement Ther Med 2005; 13(2): 87-90.
[http://dx.doi.org/10.1016/j.ctim.2005.03.006] [PMID: 16036165]
[5]
Lin X, Zhang S, Huang R, et al. Helenalin attenuates alcohol-induced hepatic fibrosis by enhancing ethanol metabolism, inhibiting oxidative stress and suppressing HSC activation. Fitoterapia 2014; 95: 203-13.
[http://dx.doi.org/10.1016/j.fitote.2014.03.020] [PMID: 24704336]
[6]
Auld CA, Hopkins RG, Fernandes KM, Morrison RF. Novel effect of helenalin on Akt signaling and Skp2 expression in 3T3-L1 preadipocytes. Biochem Biophys Res Commun 2006; 346(1): 314-20.
[http://dx.doi.org/10.1016/j.bbrc.2006.05.117] [PMID: 16750815]
[7]
Drogosz J, Janecka A. Helenalin - a sesquiterpene lactone with multidirectional activity. Curr Drug Targets 2019; 20(4): 444-52
[PMID: 30317996]
[8]
Dirsch VM, Stuppner H, Vollmar AM. Helenalin triggers a CD95 death receptor-independent apoptosis that is not affected by overexpression of Bcl-x(L) or Bcl-2. Cancer Res 2001; 61(15): 5817-23.
[PMID: 11479221]
[9]
Berges C, Fuchs D, Opelz G, Daniel V, Naujokat C. Helenalin suppresses essential immune functions of activated CD4+ T cells by multiple mechanisms. Mol Immunol 2009; 46(15): 2892-901.
[http://dx.doi.org/10.1016/j.molimm.2009.07.004] [PMID: 19656571]
[10]
Petrova M, Zayova E, Vassilevska-Ivanova R, Vlahova M. Biotechnological approaches for cultivation and enhancement of secondary metabolites in Arnica montana L.. Acta Physiol Plant 2012; 123-33.
[http://dx.doi.org/10.1007/s11738-012-0987-x]
[11]
Committee for veterinary medicinal products-Arnica montana. European agency for the evaluation of medicinal products, veterinary medicinal evaluation unit. 1999
[12]
Majoie B. Process for obtaning an extract of Arnica montana. US 3832343, 1974.
[13]
Durand GAH, Durand F. Plant extract obtained by an extraction method by means of solvents of plant origin. US20090306386, 2009.
[14]
Merfort I, Pietta PG, Mauri PL, Zini L, Catalano G, Willuhn G. Separation of sesquiterpene lactones from Arnicae Flos DAB 10 by micellar electrokinetic chromatography. Phytochem Anal 1997; 8: 5-8.
[http://dx.doi.org/10.1002/(SICI)1099-1565(199701)8:1<5::AID-PCA323>3.0.CO;2-K]
[15]
Willuhn G, Rttger PM, Matthiesen U. Helenalin- and 11,13-dihydrohelenalinester from flowers of Arnica montana. Planta Med 1983; 49(12): 226-31.
[http://dx.doi.org/10.1055/s-2007-969856] [PMID: 17405058]
[16]
Kratz F. Combination of drugs with protein-binding prodrugs. EP2560688, 2013.
[17]
Jordan A, Waldoefner N, Scholz R. Method for encapsulating therapeutic substances in cells. CA2619278, 2007.
[18]
Karimian H, Fadaeinasab M, Moghadamtousi SZ, et al. The Chemopreventive effect of tanacetum polycephalum against LA7-induced breast cancer in rats and the apoptotic effect of a cytotoxic sesquiterpene lactone in MCF7 cells: A bioassay-guided approach. Cell Physiol Biochem 2015; 36(3): 988-1003.
[http://dx.doi.org/10.1159/000430273] [PMID: 26087920]
[19]
Yosuke T, Hiroshi T, Shinjiro S. Cell death induction reagent, cell inhibitory effect reagent and for treat by the extremely caused disease of cell Proliferation medical composition. CN108064172, 2018.
[20]
Attardo GG, Belleau B. Heteroanthracycline antitumor analogs. ZA199201121, 1993.
[21]
Howes MR. Prooxidant cancer chemo-suppressors and chemo-protectors and methods of use related thereto. US20190275119, 2019.
[22]
Brunner L, Dirix Y, Jani S, Tommasini R. Medical implant producing wear particles with benign body response. WO2010096053, 2009.
[23]
Qazi NG, Taneja CS, Singh J, et al. Semi-synthetic sesquiterpene lactone parthenin compound useful for cytotoxicity against cancer cell lines and anticander agent. WO2009122447, 2009.
[24]
Nakagawa-Goto K, Chen JY, Cheng YT, et al. Novel sesquiterpene lactone analogues as potent anti-breast cancer agents. Mol Oncol 2016; 10(6): 921-37.
[http://dx.doi.org/10.1016/j.molonc.2016.03.002] [PMID: 27055598]
[25]
Finley C, Bestwick PH. Cannabis oil compositions and methods for preparation thereof. CA3006182, 2017.
[26]
Beekman AC, Woerdenbag HJ, van Uden W, et al. Structure-cytotoxicity relationships of some helenanolide-type sesquiterpene lactones. J Nat Prod 1997; 60(3): 252-7.
[http://dx.doi.org/10.1021/np960517h] [PMID: 9090867]
[27]
Kordi S, Zarghami N, Akbarzadeh A, et al. A comparison of the inhibitory effect of nano-encapsulated helenalin and free helenalin on telomerase gene expression in the breast cancer cell line, by real-time PCR. Artif Cells Nanomed Biotechnol 2016; 44(2): 695-703.
[http://dx.doi.org/10.3109/21691401.2014.981270] [PMID: 25435410]
[28]
Ghasemali S, Nejati-Koshki K, Tafsiri E, et al. Inhibitory effects of I -cyclodextrin-helenalin complexes on H-TERT gene expression in the T47D breast cancer cell line - results of real time quantitative PCR. Asian Pac J Cancer Prev 2013; 14(11): 6949-53.
[http://dx.doi.org/10.7314/APJCP.2013.14.11.6949] [PMID: 24377631]
[29]
Fernandes KM, Auld CA, Hopkins RG, Morrison RF. Helenalin -mediated post-transcriptional regulation of p21(Cip1) inhibits 3T3-L1 preadipocyte proliferation. J Cell Biochem 2008; 105(3): 913-21.
[http://dx.doi.org/10.1002/jcb.21894] [PMID: 18729080]
[30]
Wang Y, Wu H, Wu X, Bian Z, Gao Q. Interleukin 17A promotes gastric cancer invasiveness via NF-I B mediated matrix metalloproteinases 2 and 9 expression. PLoS One 2014; 9(6): e96678
[http://dx.doi.org/10.1371/journal.pone.0096678] [PMID: 24905806]
[31]
Chen D, Cao G, Qiao C, Liu G, Zhou H, Liu Q. Alpha B-crystallin promotes the invasion and metastasis of gastric cancer via NF-I B-induced epithelial-mesenchymal transition. J Cell Mol Med 2018; 22(6): 3215-22.
[http://dx.doi.org/10.1111/jcmm.13602] [PMID: 29566309]
[32]
Jang JH, Iqbal T, Min KJ, et al. Helenalin-induced apoptosis is dependent on production of reactive oxygen species and independent of induction of endoplasmic reticulum stress in renal cell carcinoma. Toxicol. In Vitro 2013; 27(2): 588-96.
[http://dx.doi.org/10.1016/j.tiv.2012.10.014] [PMID: 23123298]
[33]
Powis G, Gallegos A, Abraham RT, et al. Increased intracellular Ca2+ signaling caused by the antitumor agent helenalin and its analogues. Cancer Chemother Pharmacol 1994; 34(4): 344-50.
[http://dx.doi.org/10.1007/BF00686043] [PMID: 8033301]
[34]
Hoffmann R, von Schwarzenberg K, López-Antón N, et al. Helenalin bypasses Bcl-2-mediated cell death resistance by inhibiting NF-I B and promoting reactive oxygen species generation. Biochem Pharmacol 2011; 82(5): 453-63.
[http://dx.doi.org/10.1016/j.bcp.2011.05.029] [PMID: 21669190]
[35]
Harikumar KB. Complementary and Alternative Medicines in Prostate Cancer: A comprehensive review. 1st ed. CRC Press: Boca Raton, FL, USA 2016.
[36]
Jakobs A, Steinmann S, Henrich SM, Schmidt TJ, Klempnauer KH. Helenalin acetate, a natural sesquiterpene lactone with anti-inflammatory and anti-cancer activity, disrupts the cooperation of CCAAT box/enhancer-binding protein I (C/EBPI ) and co-activator p300. J Biol Chem 2016; 291(50): 26098-108.
[http://dx.doi.org/10.1074/jbc.M116.748129] [PMID: 27803164]
[37]
Jin F, Liu X, Zhou Z, et al. Activation of nuclear factor-kappaB contributes to induction of death receptors and apoptosis by the synthetic retinoid CD437 in DU145 human prostate cancer cells. Cancer Res 2005; 65(14): 6354-63.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-4061] [PMID: 16024638]
[38]
Inohara S, Kishida N, Konishi M. Androgen receptor-binding inhibitor. JP2007230916, 2010.
[39]
Helgason C, Crea F, Wang Y, et al. Methods and uses for diagnosis and treatment of prostate cancer. WO2014205555, 2014.
[40]
Cagir A, Kasapler P, Cakmak YO. A new class of highly apoptotic anti-cancer agents. WO2011099947A1 , 2018.
[41]
Attardo GG, Belleau B. Heteroanthracycline antitumor analogs. US5348946A , 1994.
[42]
Gertsch J, Sticher O, Schmidt T, Heilmann J. Influence of helenanolide-type sesquiterpene lactones on gene transcription profiles in Jurkat T cells and human peripheral blood cells: Anti-inflammatory and cytotoxic effects. Biochem Pharmacol 2003; 66(11): 2141-53.
[http://dx.doi.org/10.1016/j.bcp.2003.08.006] [PMID: 14609739]
[43]
Ren Y, Yu J, Kinghorn AD. Development of anticancer agents from plant-derived sesquiterpene lactones. Curr Med Chem 2016; 23(23): 2397-420.
[http://dx.doi.org/10.2174/0929867323666160510123255] [PMID: 27160533]
[44]
Lee KH, Anuforo DC, Huang ES, Piantadosi C. Antitumor agents. I. Augustibalin, a new cytotoxic sesquiterpene lactone from Balduina angustifolia (Pursh.) Robins. J Pharm Sci 1972; 61(4): 626-8.
[http://dx.doi.org/10.1002/jps.2600610431] [PMID: 4335374]
[45]
Li J, Lau G, Chen L, et al. Interleukin 23 promotes hepatocellular carcinoma metastasis via NF-kappa B induced matrix metalloproteinase 9 expression. PLoS One 2012; 7(9): e46264
[http://dx.doi.org/10.1371/journal.pone.0046264] [PMID: 23050001]
[46]
Lui NILO, Lee WKT. Combination use of CD47 antibodies/inhibitors with sorafenib for treatment of liver cancer. US20170071918, 2017.
[47]
Chapman DE, Holbrook DJ, Chaney SG, Hall IH, Lee KH. In vivo and in vitro effects of helenalin on mouse hepatic microsomal cytochrome P450. Biochem Pharmacol 1991; 41(2): 229-35.
[http://dx.doi.org/10.1016/0006-2952(91)90481-J] [PMID: 1989634]
[48]
Gorman J. Novel regimens for treating diseases and disorders. US20080019975, 2008.
[49]
Grippo AA, Hall IH, Kiyokawa H, Muraoka O, Shen YC, Lee KH. The cytotoxicity of helenalin, its mono and difunctional esters, and related sesquiterpene lactones in murine and human tumor cells. Drug Des Discov 1992; 8(3): 191-206.
[PMID: 1525302]
[50]
Kim SH, Oh SM, Kim TS. Induction of human leukemia HL-60 cell differentiation via a PKC/ERK pathway by helenalin, a pseudoguainolide sesquiterpene lactone. Eur J Pharmacol 2005; 511(2-3): 89-97.
[http://dx.doi.org/10.1016/j.ejphar.2005.02.008] [PMID: 15792776]
[51]
Hall IH, Grippo AA, Lee KH, Chaney SG, Holbrook DJ. Effect of helenalin and bis(helenalinyl)malonate on nucleic acid and protein synthesis in human KB carcinoma cells. Pharm Res 1987; 4(6): 509-14.
[http://dx.doi.org/10.1023/A:1016435807362] [PMID: 2907784]
[52]
Zwicker P, Schultze N, Niehs S, et al. Differential effects of Helenalin, an anti-inflammatory sesquiterpene lactone, on the proteome, metabolome and the oxidative stress response in several immune cell types. Toxicol. In Vitro 2017; 40: 45-54.
[http://dx.doi.org/10.1016/j.tiv.2016.12.010] [PMID: 27998807]
[53]
Faustman LD. Methods for expansion or depletion of t-regulatory cells. US20180161370, 2018.
[54]
Kratz F, Merfort I. Dual acting prodrugs. WO2008098789, 2008.
[55]
Reid BC, Collins TQ. Compositions of natural extracts and use thereof in methods for preventing or treating diseases. US20190224193, 2017.
[56]
Hans-Eric C, Magnus B. Use of Ltb4 inhibitors for the treatment of b-cell leukemias and lymphomas. US20080081835, 2008.
[57]
Dudakov J, Kinsella S. Compositions and methods to promote thymic regeneration. WO2019140300, 2019.
[58]
Huang H. Methods and materials for treating cancer. WO2019169145A1 , 2019.
[59]
Tergaonkar V. Telomerase inhibitors for use in therapy. US20150232856, 2015.
[60]
Bell IR, Sarter B, Koithan M, et al. Integrative nanomedicine: treating cancer with nanoscale natural products. Glob Adv Health Med 2014; 3(1): 36-53.
[http://dx.doi.org/10.7453/gahmj.2013.009] [PMID: 24753994]
[61]
Doi K. Agent for inhibiting increase in expression of stem cell factor and agent for inhibiting increase in expression of basic fibroblast growth factor. JP2008169118, 2008.
[62]
Korsun BF, Kuhara PS. Agent for treatment of patients with uterus myoma as hormone-dependent tumor and method of its realization. RU2145232, 2000.
[63]
Solecki B. Cannabis root extract, method of manufacture, method of use. WO2019195943, 2019.
[64]
Mc Clung HJ. Composition for topical application to skin. US6579543, 2003.
[65]
Bebirakuadamute MP, Seronos BM. Systems and methods for characterizing a biological condition or agent using calibrated gene expression profiles. KR20020079364, 2002.
[66]
Polich JN. Homeopathic therapeutic method and compositions. US20160324910, 2016.
[67]
Kurzrock R, Li L, Mehta K, Aggarawal BB, Helson L. Liposomal curcumin for treatment of diseases. US20140322303, 2014.
[68]
Aioi A. Inflammatory mediator production inhibitor and skin care agent for external use containing the same. JP2011178705, 2011.
[69]
Paradise L. Homeopathic pharmaceutical compositions. US5795573, 1998.
[70]
Archer KH, Pettit SM. Analgesic and antiphlogistic compositions and therapeutic wrap for topical delivery. US 5976547, 1999.
[71]
Garruto AJ, Widgerow DA. Compositions and methods for invasive and non-invasive procedural skincare. US10286030, 2019.
[72]
Costin JM, Williams JM. Compositions and methods for treating and preventing joint pain. WO2019106574, 2019.
[73]
Elliot P. Methods for treatment of inflammatory diseases. US20010003753, 2001.
[74]
Li Liu. Traditional chinese medicine liquid for treating skin itch and preparation method. CN103893495, 2014.
[75]
Babish J, Howell T, Pacioretty L. Compositions exhibiting synergistic inhibition of the expression and/or activity of clyclooxygenase-2. US20020077350, 2002.
[76]
Oswal DG, Oswal GP. A homeopathic formulation. EP2296681, 2011.
[77]
Roland L. Nasal spray containing a plant extract for the treatment of diseases such as herpes zoster, hematoma, mastitis and cardiovasculatory weakness. EP1374883, 2004.
[78]
Gabriele V. Cyclohexyl carbamate compounds as skin and/or hair lightening actives. EP2593077, 2016.
[79]
Grollier FJ, Alec J, Fourcadier C, Rosenbaum G, Darmenton P. Cosmetic composition for the treatment of the hair and skin comprising a powder of flowers or flower tops and a cohes on agen. US4459285, 1984.
[80]
Schneider E, Ferone J. Skin care preparation. US4973473A, 1990.
[81]
Soudant E, Nadaud J. Use of a growth factor in a slimming composition. US5436230, 1995.
[82]
Bissette LD. Method of reducing cellulite in mamalian skin. US5962482, 1999.
[83]
Kirzinger H. Anti-stress agents for aquatic animals. US6306453, 2001.
[84]
Tyrrell D Lange B Krzysik D. Antioxidant-containing wipes and absorbent products. WO2004045575, 2004.
[85]
Hersh T. Reparatives for chemosurgery and laser (thermal) therapy. US6630442B1, 2003.
[86]
Forman Y, Maabarot K, Levin O, Friedman D, Friedman KM. Effervescent granules. US59484397, 1999.
[87]
Hoffmann H, Roreger M. Hydrophilic pressure sensitive hot-meltadhesives. US6190689, 2001.
[88]
Dirksing SR, Errey JP, Johnson LT. Cosmetic or dermapharmaceutical patch. WO2001001816, 2001.
[89]
Alam M. Topical Arnica treatment for reducing bruising. US20090104292, 2009.
[90]
Yichun L. Nasal sticker for removing blackheads and shrinking pores. CN106511201, 2017.
[91]
Assessment report on Arnica montanaL. flos. European Medicines Agency (Science medicines agency) EMA/HMPC/198794/2012, 2012; 1-25.
[92]
Iannitti T, Morales-Medina JC, Bellavite P, Rottigni V, Palmieri B. Effectiveness and safety of Arnica montana in post-surgical setting, pain and inflammation. Am J Ther 2016; 23(1): e184-97.
[http://dx.doi.org/10.1097/MJT.0000000000000036] [PMID: 25171757]
[93]
Savage RH, Roe PF. A further double blind trial to assess the benefit of Arnica montana in acute stroke illness. Br Homeopath J 1978; 67: 210-22.
[http://dx.doi.org/10.1016/S0007-0785(78)80008-8]
[94]
Kaziro GSN. Metronidazole (Flagyl) and Arnica Montana in the prevention of post-surgical complications, a comparative placebo controlled clinical trial. Br J Oral Maxillofac Surg 1984; 22(1): 42-9.
[http://dx.doi.org/10.1016/0266-4356(84)90007-X] [PMID: 6365158]
[95]
LAkken P, Straumsheim PA, Tveiten D, Skjelbred P, Borchgrevink CF. Effect of homoeopathy on pain and other events after acute trauma: Placebo controlled trial with bilateral oral surgery. BMJ 1995; 310(6992): 1439-42.
[http://dx.doi.org/10.1136/bmj.310.6992.1439] [PMID: 7613277]
[96]
Hart O, Mullee MA, Lewith G, Miller J. Double-blind, placebo- controlled, randomized clinical trial of homoeopathic Arnica C30 for pain and infection after total abdominal hysterectomy. J R Soc Med 1997; 90(2): 73-8.
[http://dx.doi.org/10.1177/014107689709000205] [PMID: 9068434]
[97]
Ernst E. The benefits of Arnica: 16 case reports. Homeopathy 2003; 92(4): 217-9.
[http://dx.doi.org/10.1016/j.homp.2003.07.001] [PMID: 14587689]
[98]
Vickers AJ, Fisher P, Smith C, Wyllie SE, Rees R. Homeopathic Arnica 30x is ineffective for muscle soreness after long-distance running: A randomized, double-blind, placebo-controlled trial. Clin J Pain 1998; 14(3): 227-31.
[http://dx.doi.org/10.1097/00002508-199809000-00009] [PMID: 9758072]
[99]
Baillargean L, Drouin J, Desjardins L, Leroux D, Audet D. The effects of Arnica montana on bleeding time. A randomized clinical trial. Biomed Therap 1998; 16: 272-6.
[100]
Ramelet AA, Buchheim G, Lorenz P, Imfeld M. Homeopathic Arnica in postoperative haematomas: A double-blind study. Dermatology (Basel) 2000; 201(4): 347-8.
[http://dx.doi.org/10.1159/000051551] [PMID: 11146347]
[101]
Alonso D, Lazarus MC, Baumann L. Effects of topical Arnica gel on post-laser treatment bruises. Dermatol Surg 2002; 28(8): 686-8.
[PMID: 12174058]
[102]
Jeffrey SL, Belcher HJ. Use of Arnica to relieve pain after carpal-tunnel release surgery. Altern Ther Health Med 2002; 8(2): 66-8.
[PMID: 11892685]
[103]
Stevinson C, Devaraj VS, Fountain-Barber A, Hawkins S, Ernst E, Homeopathic E. Homeopathic Arnica for prevention of pain and bruising: Randomized placebo-controlled trial in hand surgery. J R Soc Med 2003; 96(2): 60-5.
[http://dx.doi.org/10.1177/014107680309600203] [PMID: 12562974]
[104]
Widrig R, Suter A, Saller R, Melzer J. Choosing between NSAID and Arnica for topical treatment of hand osteoarthritis in a randomised, double-blind study. Rheumatol Int 2007; 27(6): 585-91.
[http://dx.doi.org/10.1007/s00296-007-0304-y] [PMID: 17318618]
[105]
Paris A, Gonnet N, Chaussard C, et al. Effect of homeopathy on analgesic intake following knee ligament reconstruction: A phase III monocentre randomized placebo controlled study. Br J Clin Pharmacol 2008; 65(2): 180-7.
[http://dx.doi.org/10.1111/j.1365-2125.2007.03008.x] [PMID: 18251757]
[106]
Karow JH, Abt HP, FrAhling M, Ackermann H. Efficacy of Arnica montana D4 for healing of wounds after Hallux valgus surgery compared to diclofenac. J Altern Complement Med 2008; 14(1): 17-25.
[http://dx.doi.org/10.1089/acm.2007.0560] [PMID: 18199022]
[107]
Adkison JD, Bauer DW, Chang T. The effect of topical Arnica on muscle pain. Ann Pharmacother 2010; 44(10): 1579-84.
[http://dx.doi.org/10.1345/aph.1P071] [PMID: 20807867]
[108]
Cornu C, Joseph P, Gaillard S, et al. No effect of a homoeopathic combination of Arnica montana and Bryonia alba on bleeding, inflammation, and ischaemia after aortic valve surgery. Br J Clin Pharmacol 2010; 69(2): 136-42.
[http://dx.doi.org/10.1111/j.1365-2125.2009.03574.x] [PMID: 20233176]
[109]
Goedemans A, Liang K, Bennett PN. Topical Arnica and mucopolysaccharide polysulfate (Hirudoid) to decrease bruising and pain associated with haemodialysis cannulation related infiltration: A pilot study. Renal Soc Australas J 2014; 10: 62-5.


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VOLUME: 15
ISSUE: 2
Year: 2020
Published on: 02 July, 2020
Page: [132 - 142]
Pages: 11
DOI: 10.2174/1574892815666200702142601
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