Is the systemic administration of arnica extracts safe? A systematic review of preclinical trials

Authors

DOI:

https://doi.org/10.33448/rsd-v10i8.17257

Keywords:

Administration; Oral; Arnica; Injections; Intraperitoneal; Systematic review; Toxicity.

Abstract

“Arnica” extracts are widely used in folk medicine to treat acute and chronic inflammatory ailments. Nevertheless, their toxic effects upon systemic use are still not fully understood. Therefore, this work provides a systematic review on the safety of arnica extracts following preclinical trials covering their oral and intraperitoneal administration in animal models. Henceforth, PRISMA guideline was followed and the study protocol was registered in PROSPERO (CDR42020167112). Searches were performed in PubMed (MEDLINE), Scopus, Science Direct, Web of Science (Science Citation Index), and Health Virtual Library (BVS) databases; while SYRCLE’s Risk of Bias tool and CAMARADES checklist were used to assess scientific quality. From 382 articles, five studies met eligibility criteria and underwent qualitative analysis. Data of acute toxicity was reported in all the selected articles, and the treatment time was up to 14 days. Moreover, the following species were reported: Solidago chilensis (hazard categories of 4 and 5 for i.p and v.o administration, respectively); Solidago microglossa (hazard category of 3, i.p); Lychnophora trichocarpha (hazard category of ≥ 4, i.p); and Lychnophora pinaster (hazard category of ≥ 4, v.o). The alcoholic extracts showcased greater toxic potential, which increased in a dose-dependent manner after 100 mg/Kg. Concerning organ-specific toxicity, the articles reported hepatotoxicity and nephrotoxicity following histopathological analysis. However, the safety of S. chilensis, L. pinaster, L. trichocarpha, and S. microglossa following systemic administration remains unclear due to the limited experimental quality of the included papers, as well as the lack of reported chronic toxicity, pharmacokinetics, and mutagenicity studies.

References

Adams, S. S., Bough, R. G., Cliffe, E. E., Lessel, B., & Mills, R. F. N. (1969). Absorption, distribution and toxicity of ibuprofen. Toxicology and Applied Pharmacology, 15(2), 310–330. https://doi.org/10.1016/0041-008X(69)90032-5

Adamson, R. H. (2016). The acute lethal dose 50 (LD50) of caffeine in albino rats. Regulatory Toxicology and Pharmacology, 80, 274–276. https://doi.org/10.1016/j.yrtph.2016.07.011

Al Shoyaib, A., Archie, S. R., & Karamyan, V. T. (2020). Intraperitoneal Route of Drug Administration: Should it Be Used in Experimental Animal Studies? Pharmaceutical Research, 37(1). https://doi.org/10.1007/s11095-019-2745-x

Assini, F. L., Fabrício, E. J., & Lang, K. L. (2013). Efeitos farmacológicos do extrato aquoso de Solidago chilensis Meyen em camundongos. Revista Brasileira de Plantas Medicinais, 15(1), 130–134. https://doi.org/10.1590/S1516-05722013000100018

Athayde, A. E. de, Richetti, E., Wolff, J., Lusa, M. G., & Biavatti, M. W. (2019). “Arnicas” from Brazil: comparative analysis among ten species. Revista Brasileira de Farmacognosia. https://doi.org/10.1016/j.bjp.2019.02.006

Auboire, L., A. Sennoga, C., Hyvelin, J.-M., Ossant, F., Escoffre, J.-M., Tranquart, F., & Al., E. (2018). Quality assessment of the studies using the collaborative approach to meta-analysis and review of Animal Data from Experimental Studies (CAMARADES) checklist items. https://doi.org/PLOS ONE. Dataset. https://doi.org/10.1371/journal.pone.0191788.t007

Baatsch, B., Zimmer, S., Rodrigues, D., & Büssing, A. (2017). Complementary Therapies in Medicine Complementary and alternative therapies in dentistry and characteristics of dentists who recommend them. Complementary Therapies in Medicine, 35, 64–69. https://doi.org/10.1016/j.ctim.2017.08.008

Bernardes, A. C. F. P. F., Matosinhos, R. C., de Paula Michel Araújo, M. C., Barros, C. H., de Oliveira Aguiar Soares, R. D., Costa, D. C., Sachs, D., & Saúde-Guimarães, D. A. (2021). Sesquiterpene lactones from Lychnophora species: Antinociceptive, anti-inflammatory, and antioxidant pathways to treat acute gout. Journal of Ethnopharmacology, 269, 113738. https://doi.org/https://doi.org/10.1016/j.jep.2020.113738

Bertin, H. (1864). A case report of poisoning by tincture of arnica. The Lancet, 571. https://doi.org/10.1016/s0140-6736(02)88947-4

Bolson, M., Hefler, S. R., Chaves, E. I. D., Junior, A. G., & Junior, E. L. C. (2015). Ethno-medicinal study of plants used for treatment of human ailments , with residents of the surrounding region of forest fragments of Paraná, Brazil. Journal of Ethnopharmacology, 161, 1–10. https://doi.org/10.1016/j.jep.2014.11.045

Bracken, M. B. (2009). Why animal studies are often poor predictors of human reactions to exposure. Journal of the Royal Society of Medicine, 102(3), 120–122. https://doi.org/10.1258/jrsm.2008.08k033

BRASIL. (2004). Ministério da Saúde. Agência Nacional de Vigilância Sanitária. RESOLUÇÃO-RE No90, DE 16 DE MARÇO DE 2004. Determina a publicação do guia para a realização de estudos de toxicidade pré-clínica de fitoterápicos. (pp. 14–15).

BRASIL. (2009). Ministério da Saúde. Agência Nacional de Vigilância SanitáriaRelação de Plantas Medicinais de Interesse ao Sistema Único de Saúde (RENISUS). http://bvsms.saude.gov.br/bvs/sus/pdf/marco/ms_relacao_plantas_medicinais_sus_0603.pdf

BRASIL. (2021). Ministério da Saúde. Agência Nacional de Vigilância Sanitária. Diretoria Colegiada. INSTRUÇÃO NORMATIVA IN No 86, DE 12 DE MARÇO DE 2021 Define a Lista de Medicamentos Isentos de Prescrição.

Bucciarelli, A., Minetti, A., Milczakowskyg, C., & Skliar, M. (2010). Evaluation of gastroprotective activity and acute toxicity of Solidago chilensis Meyen (Asteraceae). Pharmaceutical Biology, 48(9), 1025–1030. https://www.ncbi.nlm.nih.gov/pubmed/20731555

Bushra, R., & Aslam, N. (2010). An overview of clinical pharmacology of ibuprofen. Oman Medical Journal, 25(3), 155–161. https://doi.org/10.5001/omj.2010.49

Caldeira, T. G., Saúde-Guimarães, D. A., Lacerda, D. L. R. de, Mussel, W. da N., Yoshida, M. I., & Souza, J. De. (2019). Polymorphic characterization and implications on biopharmaceutics properties of potential anti-inflammatory drug candidate eremantholide C from Lychnophora trichocarpha (Brazilian Arnica). Journal of Pharmacy and Pharmacology, 1–10. https://doi.org/10.1111/jphp.13080

Canders, C. P., Stanford, S. R., & Chiem, A. T. (2014). A Dangerous Cup of Tea. Wilderness & Environmental Medicine, 25, 111–112. https://doi.org/10.1016/j.wem.2013.11.002

Carvalho, A. C. B., Lana, T. N., Perfeito, J. P. S., & Silveira, D. (2018). The Brazilian market of herbal medicinal products and the impacts of the new legislation on traditional medicines. Journal of Ethnopharmacology, 212, 29–35. https://doi.org/10.1016/j.jep.2017.09.040

Colalto, C. (2018). What phytotherapy needs: Evidence ‐ based guidelines for better clinical practice. Phytotherapy Research, 32, 413–425. https://doi.org/10.1002/ptr.5977

Colombo, M. L., Assisi, F., Puppa, T. Della, Moro, P., Sesana, F. M., Bissoli, M., Borghini, R., Perego, S., Galasso, G., Banfi, E., & Davanzo, F. (2010). Exposures and intoxications after herb-induced poisoning: A retrospective hospital-based study. Journal of Pharmaceutical Sciences and Research, 2(2), 123–136.

Couto, R. O. do, Chequer, F. M. D., & Oliveira, V. M. (2020). Does the internal use of arnica is safe? a systematic review of animal preclinical studies. PROSPERO CRD42020167112, 1–9.

da Silva Prade, J., Bálsamo, E. C., Machado, F. R., Poetini, M. R., Bortolotto, V. C., Araújo, S. M., Londero, L., Boeira, S. P., Sehn, C. P., de Gomes, M. G., Prigol, M., & Cattelan Souza, L. (2020). Anti-inflammatory effect of Arnica montana in a UVB radiation-induced skin-burn model in mice. Cutaneous and Ocular Toxicology, 39(2), 126–133. https://doi.org/10.1080/15569527.2020.1743998

de Athayde, A. E., de Araujo, C. E. S., Sandjo, L. P., & Biavatti, M. W. (2021). Metabolomic analysis among ten traditional “Arnica” (Asteraceae) from Brazil. Journal of Ethnopharmacology, 265, 113149. https://doi.org/https://doi.org/10.1016/j.jep.2020.113149

de Barros, M., da Silva, L., Boeing, T., Somensi, L. B., Cury, B. J., de Moura Burci, L., Santin, J. R., de Andrade, S. F., Monache, F. D., & Cechinel-Filho, V. (2016). Pharmacological reports about gastroprotective effects of methanolic extract from leaves of Solidago chilensis (Brazilian arnica) and its components quercitrin and afzelin in rodents. Naunyn-Schmiedeberg’s Archives of Pharmacology, 389(4), 403–417.

de Sá Müller, C., Coelho, G. B., de Paula Michel Araújo, M., & Saúde-Guimarães, D. A. (2019). Lychnophora pinaster ethanolic extract and its chemical constituents ameliorate hyperuricemia and related inflammation. Journal of Ethnopharmacology, 242, 112040.

de Souza, M. R., de Paula, C. A., de Resende, M. L., Grabe-Guimarães, A., de Souza Filho, J. D., & Saúde-Guimarães, D. A. (2012). Pharmacological basis for use of Lychnophora trichocarpha in gouty arthritis: Anti-hyperuricemic and anti-inflammatory effects of its extract, fraction and constituents. Journal of Ethnopharmacology, 142(3), 845–850.

de Vries, R. B. M., Hooijmans, C. R., Langendam, M. W., van Luijk, J., Leenaars, M., Ritskes-Hoitinga, M., & Wever, K. E. (2015). A protocol format for the preparation, registration and publication of systematic reviews of animal intervention studies. Evidence-Based Preclinical Medicine, 2(1), e00007. https://doi.org/10.1002/ebm2.7

Dolisgan, K. K., Kiani, A. A., Galehdar, N., & Moradifar, N. (2020). A systematic review of antihypertensive effects of medical plants in Asteracae family. Journal of Critical Reviews, 7(14), 1525–1530.

Dos Santos, L., Viel, A. M., Tarosso, L. F., Momesso, L. da S., Palmieri, D. A., & Spera, K. D. (2020). Medicinal plants of the brazilian cerrado: Knowing to preserve. Bioscience Journal, 36(2), 556–567. https://doi.org/10.14393/BJ-v36n2a2020-42748

Dutra, R. C., Campos, M. M., Santos, A. R. S., & Calixto, J. B. (2016). Medicinal plants in Brazil: Pharmacological studies, drug discovery, challenges and perspectives. Pharmacological Research, 112, 4–29. https://doi.org/10.1016/j.phrs.2016.01.021

Facury Neto, M. A., Fagundes, D. J., Beletti, M. E., Novo, N. F., Juliano, Y., & Penha-Silva, N. (2004). Systemic use of Solidago microglossa DC in the cicatrization of open cutaneous wounds in rats. Braz J Morphol Sci, 21, 207–210.

Ferrari, F. C., Grabe-Guimarães, A., Carneiro, C. M., de Souza, M. R., Ferreira, L. C., de Oliveira, T. T., & Saúde-Guimarães, D. A. (2012). Toxicological evaluation of ethanolic extract of Lychnophora trichocarpha, Brazilian arnica. Brazilian Journal of Pharmacognosy, 22(5), 1104–1110. https://doi.org/10.1590/S0102-695X2012005000089

Ferreira, S A, Guimarães, A. G., Ferrari, F. C., Carneiro, C. M., de Paiva, N. C. N., & Guimarães, D. A. S. (2014). Assessment of acute toxicity of the ethanolic extract of Lychnophora pinaster (Brazilian arnica). Brazilian Journal of Pharmacognosy, 24(5), 553–560.

Ferreira, S A., Grabe-Guimarães, A., Assis, N. A., & Saúde-Guimarães, D. A. (2019). Efeitos anti-inflamatório tópico e antinociceptivo do extrato etanólico de Lychnophora pinaster (Arnica Brasileira). Brazilian Journal of Health and Pharmacy, 1(1), 26–39. https://doi.org/10.29327/226760.1.1-4

Gras, A., Hidalgo, O., D’Ambrosio, U., Parada, M., Garnatje, T., & Vallès, J. (2021). The Role of Botanical Families in Medicinal Ethnobotany : A Phylogenetic Perspective. Plants, 10(163), 1–17. https://doi.org/10.3390/plants10010163

Halevy, A. H. (2018). CRC Handbook of flowering. In CRC Handbook of Flowering (Vol. 5, Issue 3). https://doi.org/10.1201/9781351072571

Hooijmans, C. R., Rovers, M. M. ., Vries, R. B. ., Leenaars, M., Hoitinga Ritskes, M., & Langendam, M. W. (2014). SYRCLE’s risk of bias tool for animal studies. Medical Research Methodology, 43, 1–9. https://doi.org/10.1016/S0140-6736(02)09812-4

Hudson, A., Lopez, E., Almalki, A. J., Roe, A. L., & Calderón, A. I. (2018). A Review of the Toxicity of Compounds Found in Herbal Dietary Supplements. Planta Medica, 84, 613–626.

Iannitti, T., Morales-Medina, J. C., Bellavite, P., Rottigni, V., & Palmieri, B. (2016). Effectiveness and Safety of Arnica montana in Post-Surgical Setting , Pain and Inflammation. American Journal of Therapeutics, 23, 184–197.

Jayasundera, M., Florentine, S., Tennakoon, K. U., & Chauhan, B. S. (2021). Medicinal value of three agricultural weed species of the asteraceae family: A review. In Pharmacognosy Journal (Vol. 13, Issue 1, pp. 264–277). https://doi.org/10.5530/pj.2021.13.36

Kenny, O., Smyth, T. J., Walsh, D., Kelleher, C. T., Hewage, C. M., & Brunton, N. P. (2014). Investigating the potential of under-utilised plants from the Asteraceae family as a source of natural antimicrobial and antioxidant extracts. Food Chemistry, 161, 79–86. https://doi.org/10.1016/j.foodchem.2014.03.126

Khuda-Bukhsh, A. R., & Chakrabart, J. (1998). Effects of sonication on chromosomes of mice, Mus musculus , and modifying effects of a homeopathic drug, Arnica Montana, on them. Perspectives in Cytology and Genetics, 9, 333–340.

Kriplani, P., Guarve, K., & Baghael, U. S. (2017). Arnica montana L. – a plant of healing: review. Journal of Pharmacy and Pharmacology, 69(8), 925–945. https://doi.org/https://doi.org/10.1111/jphp.12724

Landis, J. R., & Koch, G. G. (1977). The Measurement of Observer Agreement for Categorical Data. Biometrics, 33(1), 159–174. https://doi.org/10.2307/2529310

Leenaars, C. H. C., Kouwenaar, C., Stafleu, F. R., Bleich, A., Ritskes-Hoitinga, M., De Vries, R. B. M., & Meijboom, F. L. B. (2019). Animal to human translation: A systematic scoping review of reported concordance rates. Journal of Translational Medicine, 17(1), 1–22. https://doi.org/10.1186/s12967-019-1976-2

Llorent-Martínez, E. J., Zengin, G., Sinan, K. I., Polat, R., Canlı, D., Picot-Allain, M. C. N., & Mahomoodally, M. F. (2020). Impact of different extraction solvents and techniques on the biological activities of Cirsium yildizianum (Asteraceae: Cynareae). Industrial Crops and Products, 144, 112033. https://doi.org/https://doi.org/10.1016/j.indcrop.2019.112033

Lorke, D. (1983). A new approach to practical acute toxicity testing. Archives of Toxicology, 54(4), 275–287. https://doi.org/10.1007/BF01234480

Macleod, M. R., O’Collins, T., Howells, D. W., & Donnan, G. A. (2004). Pooling of animal experimental data reveals influence of study design and publication bias. Stroke, 35(5), 1203–1208. https://doi.org/10.1161/01.STR.0000125719.25853.20

Magalhães, K. do N., Guarniz, W. A. S., Sá, K. M., Freire, A. B., Monteiro, M. P., Nojosa, R. T., Bieski, I. G. C., Custódio, J. B., Balogun, S. O., & Bandeira, M. A. M. (2019). Medicinal plants of the Caatinga, northeastern Brazil: Ethnopharmacopeia (1980–1990) of the late professor Francisco José de Abreu Matos. Journal of Ethnopharmacology, 237, 314–353. https://doi.org/https://doi.org/10.1016/j.jep.2019.03.032

Malpezzi-Marinho, E. L. A., Molska, G. R., Freire, L. I. G. P., Silva, C. I., Tamura, E. K., Berro, L. F., Parada, C. A., & Marinho, E. A. V. (2019). Effects of hydroalcoholic extract of Solidago chilensis Meyen on nociception and hypernociception in rodents. BMC Complementary and Alternative Medicine, 19(1). https://www.scopus.com/inward/record.uri?eid=2-s2.0-85063301471&doi=10.1186%2Fs12906-019-2478-8&partnerID=40&md5=504dca75ddbe1313620f0262a82a6550

Marisco, G., Silva, T. S., Assunção, R., Brendel, M., & Pungartnik, C. (2017). The Use of Herbal Medicine in a Rural Community in Vitória Da Conquista, Bahia, Brazil: An Indication for Pharmacological Studies. International Journal of Complementary & Alternative Medicine, 7(1), 1–11. https://doi.org/10.15406/ijcam.2017.07.00214

Mawardi, H., Ghazalh, S., Shehatah, A., Abdelwahid, A., Aljohani, A., Felemban, O., Almazrooa, S., Elbadawi, L., & Shawky, H. (2020). Systemic Use of Arnica Montana for the Reduction of Postsurgical Sequels following Extraction of Impacted Mandibular 3rd Molars: A Pilot Study. Evidence-Based Complementary and Alternative Medicine, 2020, 6725175. https://doi.org/10.1155/2020/6725175

Meinhart, A. D., Damin, F. M., Caldeirão, L., Teixeira-Filho, J., & Godoy, H. T. (2020). Rutin in herbs and infusions: Screening of new sources and consumption estimation. Food Science and Technology, 40(June), 113–120. https://doi.org/10.1590/fst.01219

Meinhart, A. D., Damina, F. M., Caldeirão, L., Silveira, T. F. F. da, Filho, J. T., & Godoy, H. T. (2017). Chlorogenic acid isomer contents in 100 plants commercialized in Brazil. Food Research International, 99, 522–530. https://doi.org/10.1016/j.foodres.2017.06.017

Mercandeli, A. A., Bessa, G. P., Ronchi, S. N., Segato, T. P. S., & Silva, A. G. da. (2012). Evidence for the Safe Use of the Extract from the Brazilian Arnica, Solidago chilensis Meyen. Primary Health Care. Chinese Medicine, 03(01), 4–8. https://doi.org/10.4236/cm.2012.31002

Michel, J., Abd Rani, N. Z., & Husain, K. (2020). A Review on the Potential Use of Medicinal Plants From Asteraceae and Lamiaceae Plant Family in Cardiovascular Diseases. Frontiers in Pharmacology (Vol. 11, p. 852). https://www.frontiersin.org/article/10.3389/fphar.2020.00852

Mishra, D., Joshi, S., Sah, S. P., & Bisht, G. (2011). Chemical composition, analgesic and antimicrobial activity of Solidago canadensis essential oil from India. Journal of Pharmacy Research, 4(1), 63–66. www.jpronline.info

Moher, D., Liberati, A., Tetzlaff, J., & Altman, D. G. (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses : The PRISMA Statement. Plos Medicine, 6(7), e1000097. https://doi.org/10.1371/journal.pmed.1000097

Obón, C., Rivera, D., Verde, A., Fajardo, J., Valdés, A., Alcaraz, F., & Carvalho, A. M. (2012). Árnica: A multivariate analysis of the botany and ethnopharmacology of a medicinal plant complex in the Iberian Peninsula and the Balearic Islands. Journal of Ethnopharmacology, 144(1), 44–56. https://doi.org/https://doi.org/10.1016/j.jep.2012.08.024

OECD/OCDE. (2001). Acute Oral toxicity - Acute Toxic Class Method (OECD 423). In OECD Guideline for Testing of Chemicals (Issue December). https://doi.org/10.1787/9789264071001-en

OECD/OCDE. (2008). OECD Guidelines for the Testing of Chemicals (OECD 425) - Acute Oral Toxicity – Up-and-Down-Procedure (UDP) (Issue November, pp. 1–13).

Ouzzani, M., Hammady, H., Fedorowicz, Z., & Elmagarmid, A. (2016). Rayyan — a web and mobile app for systematic reviews. Systematic Reviews, 5(210), 1–10. https://doi.org/10.1186/s13643-016-0384-4

Oyedepo, T. A., & Palai, S. (2021). Chapter 6: Herbal remedies, toxicity, and regulations. In C. Egbuna, A. P. Mishra, & M. R. B. T. Goyal (Eds.), Preparation of Phytopharmaceuticals for the Management of Disorders - The Development of Nutraceuticals and Traditional Medicine (pp. 89–127). Academic Press. https://doi.org/https://doi.org/10.1016/B978-0-12-820284-5.00014-9

Panda, S. K., da Silva, L. C. N., Sahal, D., & Leonti, M. (2019). Ethnopharmacological Studies for the Development of Drugs With Special Reference to Asteraceae. Frontiers in Pharmacology (Vol. 10, p. 955). https://www.frontiersin.org/article/10.3389/fphar.2019.00955

Paula-Freire, L. I. G., Malpezzi-Marinho, E. L. A., Molska, G. R., Kohn, D. O., Correa, L., & Marinho, E. A. V. (2014). Evaluation of the Acute Toxicity of the Hydroalcoholic Extract of Solidago chilensis Meyen ( Arnica Do Campo ) in Mice. American Journal of Phytomedicine and Clinical Therapeutics, 2(2), 217–228.

Raghibi, A., Salar, A., Askari, H., & Keykha, R. (2018). Investigating the Effect of Arnica Ointment and Distraction on the Pain Caused by Fistula Needle Insertion in Hemodialysis Patients: A Clinical Trial. Med Surg Nurs J, 7(2), 1–7. https://doi.org/10.5812/msnj.85338.Research

Ribeiro Neto, J. A., Pimenta Tarôco, B. R., Batista dos Santos, H., Thomé, R. G., Wolfram, E., & Maciel de A Ribeiro, R. I. (2020). Using the plants of Brazilian Cerrado for wound healing: From traditional use to scientific approach. Journal of Ethnopharmacology, 260(January). https://doi.org/10.1016/j.jep.2020.112547

Ribeiro, R. V., Bieski, I. G. C., Balogun, S. O., & Martins, D. T. de O. (2017). Ethnobotanical study of medicinal plants used by Ribeirinhos in the North Araguaia microregion, Mato Grosso, Brazil. Journal of Ethnopharmacology, 205, 69–102. https://doi.org/https://doi.org/10.1016/j.jep.2017.04.023

Rodrigues, D. F., Luna, S. P. L., Brondani, J. T., & Minto, B. W. (2016). Comparison of morphine, ketoprofen and arnica montana 6x and 30x per oral transmucosal or subcutaneous route for control of postoperative pain in cats subjected to hysterectomy with bilateral salpingo-oophorectomy. Ciencia Rural, 46(2), 330–335. https://www.scopus.com/inward/record.uri?eid=2-s2.0-84949796798&doi=10.1590%2F0103-8478cr20150203&partnerID=40&md5=25d8eec3e1e2c22859ac95a249953648

Rodríguez-Chávez, J. L., Egas, V., Linares, E., Bye, R., Hernández, T., Espinosa-garcía, F. J., & Delgado, G. (2017). Mexican Arnica (Heterotheca inuloides Cass . Asteraceae: Astereae): Ethnomedical uses, chemical constituents and biological properties. Journal of Ethnopharmacology, 195, 39–63. https://doi.org/10.1016/j.jep.2016.11.021

Sabir, S. M., Ahmad, S. D., Hamid, A., Khan, M. Q., Athayde, M. L., Santos, D. B., Boligon, A. A., & Rocha, J. B. T. (2012). Antioxidant and hepatoprotective activity of ethanolic extract of leaves of Solidago microglossa containing polyphenolic compounds. Food Chemistry, 131(3), 741–747. https://doi.org/10.1016/j.foodchem.2011.09.026

Saraiva, M. E., Ulisses, A. V. R. de A., Ribeiro, D. A., Oliveira, L. G. S. de, Macêdo, D. G. de, Sousa, F. de F. S. de, Menezes, I. R. A. de, Sampaio, E. V. de S. B., & Souza, M. M. de A. (2015). Plant species as a therapeutic resource in areas of the savanna in the state of Pernambuco , Northeast Brazil. Journal of Ethnopharmacology, 171, 141–153. https://doi.org/10.1016/j.jep.2015.05.034

Schneider, M., Sachett, A., Schönell, A. P., Ibagy, E., Fantin, E., Bevilaqua, F., Piccinin, G., Santo, G. D., Giachini, M., Chitolina, R., Wildner, S. M., Mocelin, R., Zanatta, L., & Roman Junior, W. A. (2015). Hypoglycemic and hypolipidemic effects of Solidago chilensis in rats. Revista Brasileira de Farmacognosia, 25(3), 258–263. http://www.sciencedirect.com/science/article/pii/S0102695X15000897

Sharma, S., Arif, M., Nirala, R. K., Gupta, R., & Thakur, S. C. (2016). Cumulative therapeutic effects of phytochemicals in Arnica montana flower extract alleviated collagen-induced arthritis: Inhibition of both pro-inflammatory mediators and oxidative stress. Journal of the Science of Food and Agriculture, 96(5), 1500–1510. https://www.scopus.com/inward/record.uri?eid=2-s2.0-84959540252&doi=10.1002%2Fjsfa.7252&partnerID=40&md5=b4c9f55f13f91538fa2d6e0bef1f104c

Shin, J., Seol, I., & Son, C. (2010). Interpretation of Animal Dose and Human Equivalent Dose for Drug Development. The Journal of Korean Oriental Medicine, 31(3), 1–7.

Silva, A. G. da, Machado, E. R., Almeida, L. M. de, Nunes, R. M. M., Giesbrecht, P. C. P., Costa, R. M., Costa, H. B., Romão, W., & Kuster, R. M. (2015). A Clinical Trial with Brazilian Arnica (Solidago chilensis Meyen) Glycolic Extract in the Treatment of Tendonitis of Flexor and Extensor Tendons of Wrist and Hand. Phytotherapy Research, 29, 864–869.

Siqueira, B. V. L., Sakuragui, C. M., Soares, B. E., & Oliveira, D. R. De. (2018). The rise of medicalization of plants in Brazil: A temporal perspective on vernacular names. Journal of Ethnopharmacology, 224(May), 535–540. https://doi.org/10.1016/j.jep.2018.06.024

Sorrentino, L., Piraneo, S., Riggio, E., Basilicò, S., Sartani, A., Bossi, D., & Corsi, F. (2017). Is there a role for homeopathy in breast cancer surgery? A first randomized clinical trial on treatment with Arnica montana to reduce post-operative seroma and bleeding in patients undergoing total mastectomy. Journal of Intercultural Ethnopharmacology, 6(1), 1–8. https://doi.org/10.5455/jice.20161229055245

Souza, J. S. S., Gomes, E. l C., Rocha, T. C., & Böger, B. (2017). Uso de plantas medicinais por comunidades do município de Curitiba. Divers@ Revista Eletrônica Interdisciplinar, 10(2), 91–97.

Stalikas, C. D. (2007). Extraction, separation, and detection methods for phenolic acids and flavonoids. Journal of Separation Science, 30(18), 3268–3295. https://doi.org/10.1002/jssc.200700261

Valverde, S. S., Souza, S. P. O., Barroso, K. T., Maia, A., Costa, N. F., Calheiros, A. S., Lima, K. S. C., Frutuoso, V. S., & Lima, A. L. S. (2020). Chemical composition and antinociceptive activity of volatile fractions of the aerial parts of Solidago chilensis (Compositae). Rodriguesia, 71: e00862019. https://doi.org/10.1590/2175-7860202071053.

van Dam, R. M., Hu, F. B., & Willett, W. C. (2020). Coffee, Caffeine, and Health. New England Journal of Medicine, 383(4), 369–378. https://doi.org/10.1056/nejmra1816604

Van Norman, G. A. (2019). Limitations of Animal Studies for Predicting Toxicity in Clinical Trials: Is it Time to Rethink Our Current Approach? JACC: Basic to Translational Science, 4(7), 845–854. https://doi.org/10.1016/j.jacbts.2019.10.008

Van Norman, G. A. (2020). Limitations of Animal Studies for Predicting Toxicity in Clinical Trials: Part 2: Potential Alternatives to the Use of Animals in Preclinical Trials. JACC: Basic to Translational Science, 5(4), 387–397. https://doi.org/10.1016/j.jacbts.2020.03.010

Vogas, R. S., Pereira, M. T. M., Duarte, L. S., Carneiro, M. J., Farsura, A. F., Machado, J. A. M. M., Costa, I. F., Tomé, M. R. N., MIilton, F. A., Neves, F. A. R., Andreo, M. A., Lopez, B. G.-C., Sawaya, A. C. H. F., Pascoal, V. D. Á. B., & Pascoal, A. C. R. F. (2020). Evaluation of the anti-inflammatory potential of Solidago microglossa (Arnica-brasileira) in vivo and its effects on PPARy activity. Anais da Academia Brasileira de Ciências, 92(2), e20191201. https://doi.org/10.1590/0001-3765202020191201

Yousuf, M. A., Devaraj, E., & Narayan, V. (2019). Asteraceae: A review of hepatoprotective plant principles. Drug Invention Today, 11, 22–24.

Zank, S., & Hanazaki, N. (2017). The coexistence of traditional medicine and biomedicine: A study with local health experts in two Brazilian regions. PLoS ONE, 12(4), 1–17. https://doi.org/10.1371/journal.pone.0174731

Zbinden, G., & Flury-Roversi, M. (1981). Significance of the LD50-test for the toxicological evaluation of chemical substances. Archives of Toxicology, 47(2), 77–99. https://doi.org/10.1007/BF00332351

Published

12/07/2021

How to Cite

OLIVEIRA, V. M. .; THOMAZ, D. V. .; BALDONI, F. M. D. C.; BALDONI, N. R. .; COUTO, R. O. do. Is the systemic administration of arnica extracts safe? A systematic review of preclinical trials. Research, Society and Development, [S. l.], v. 10, n. 8, p. e27110817257, 2021. DOI: 10.33448/rsd-v10i8.17257. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/17257. Acesso em: 5 nov. 2024.

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Section

Review Article