Evaluation of the acute toxicity, antitumor and acute inflammation inhibitory effects of Drimys brasiliensis (winteraceae)
DOI:
https://doi.org/10.21527/2176-7114.2024.48.14659Keywords:
Phytotherapy, Toxicity, Antineoplastic, Anti-inflammatory AgentsAbstract
The genus Drimys, belonging to the Winteraceae botanical family, is widely recognized and valued. Its species have been used in folk medicine to treat various health problems, such as gastric pain, toothache and anemia. In certain localities, the dried leaves and berries of the fruit are used as condiments due to their spicy flavor. This study aims to evaluate the phytochemical profile, acute toxicity, anti-inflammatory and antitumor activities of the ethanolic leaf extract of Drimys brasiliensis. In this study, we conducted an analysis of the phytochemical profile and quantification of phenolic and flavonoids compounds. We evaluated the acute toxicity administering a dose of 2000 mg.kg-1 in mice. Futhermore, we investigated the anti-inflammatory activity using experimental models of paw edema, peritonitis and air pouch, and carried out an antitumor test using the 180-sarcoma model. Chromatographic analysis revealed the presence of anthocyanidins, phenolic compounds, coumarins, anthracene derivatives, terpenes, naphthoquinones, saponins and triterpenes. The extract showed a large amount of phenolic and flavonoids compounds. We also observed low toxicity in rodents, with an LD50 greater than 2000 mg.kg-1. Additionally, we verified that the extract showed inhibition of leukocytes and neutrophils at the tested doses of 50, 100 and 200 mg.kg-1. In the paw edema model, the concentrations of 100 and 200 mg.kg-1 were statistically different (p<0.05). In the 180-sarcoma model, the dose of 300 mg.kg-1 resulted in tumor inhibition of 64.33%. In view of these promising results, further studies are needed to better understand the bioavailability and pharmacokinetics of the plant extract.
References
Huang L, LaBonte MJ, Craig SG, Finn SP, Allott EH. Inflammation and Prostate Cancer: A Multidisciplinary Approach to Identifying Opportunities for Treatment and Prevention. Cancers. 2022;14(6):1367. doi:10.3390/cancers14061367
Neganova M, Liu J, Aleksandrova Y, Klochkov S, Fan R. Therapeutic Influence on Important Targets Associated with Chronic Inflammation and Oxidative Stress in Cancer Treatment. Cancers. 2021;13(23):6062. doi:10.3390/cancers13236062
Nigam M, Mishra A P, Deb V K, Dimri, D B, Tiwari V, Bungau S G, Bungau A F, Radu A-F. Evaluation of the association of chronic inflammation and cancer: Insights and implications. Biomedicine & Pharmacotherapy. 2023; 164: 115015. doi: 10.1016/j.biopha.2023.115015
Greten F R, Sergei I G. Inflammation and Cancer: triggers, mechanisms, and consequences. Immunity. 2019; 51 (1):27-41. doi: 10.1016/j.immuni.2019.06.025
Baek AE. Bacteria benefit tumor cells. Sci Signal. 2022;15(729):eabq4492. doi:10.1126/scisignal.abq4492
Shawki S, Ashburn J, Signs SA, Huang E. Colon Cancer: Inflammation Associated Cancer. Surg Oncol Clin N Am. 2018;27(2):269-287. doi:10.1016/j.soc.2017.11.003
Bujak JK, Kosmala D, Szopa IM, Majchrzak K, Bednarczyk P. Inflammation, Cancer and Immunity-Implication of TRPV1 Channel. Front Oncol. 2019;9. https://www.frontiersin.org/articles/10.3389/fonc.2019.01087
Ramos-Inza S, Ruberte AC, Sanmartín C, Sharma AK, Plano D. NSAIDs: Old Acquaintance in the Pipeline for Cancer Treatment and Prevention─Structural Modulation, Mechanisms of Action, and Bright Future. J Med Chem. 2021;64(22):16380-16421. doi: 10.1021/acs.jmedchem.1c01460
Fiorentino S, Urueña C, Fiorentino S, Urueña C. La fitoterapia como fuente de medicamentos reguladores del metabolismo tumoral y activadores de la respuesta inmunitaria. Rev Acad Colomb Ciencas Exactas Físicas Nat. 2018;42(163):132-144. doi:10.18257/raccefyn.542
Ochwang'i DO, Kimwele CN, Oduma JA, Gathumbi PK, Kiama SG, Efferth T. Cytotoxic activity of medicinal plants of the Kakamega County (Kenya) against drug-sensitive and multidrug-resistant cancer cells. J Ethnopharmacol. 2018;215:233-240. doi:10.1016/j.jep.2018.01.004
Teodor ED, Ungureanu O, Gatea F, Radu GL. The Potential of Flavonoids and Tannins from Medicinal Plants as Anticancer Agents. Anticancer Agents Med Chem. 2020;20(18):2216-2227. doi:10.2174/1871520620666200516150829
Flora and fungi of Brazil - Drimys J.R.Forst. & G.Forst. Accessed June 15, 2023. http://floradobrasil.jbrj.gov.br/reflora/floradobrasil/FB15323
Tropicos | Name - !!Drimys J.R. Forst. & G. Forst. Missouri Botanical Garden. Accessed June 15, 2023. http://legacy.tropicos.org/Name/40035760
Mariot A, Mantovani A, Bittencourt R, Ferreira DK, Reis MS. Population structure and annual current increment of casca-de-anta (Drimys brasiliensis Miers - Winteraceae) in Caçador, Santa Catarina, Brazil. Rev Bras Plantas Med. 2010;12:168-178. doi:10.1590/S1516- 05722010000200008
Lorenzi H, Matos FJ de A. Plantas medicinais no Brasil: nativas e exóticas. Instituto Plantarum de Estudos da Flora; 2002
Wagner H, Bladt S. Plant Drug Analysis: A Thin Layer Chromatography Atlas. Springer Science & Business Media; 1996
Singleton VL, Orthofer R, Lamuela-Raventós RM. Analysis of total phenols and other oxidation substrates and antioxidants by means of folin-ciocalteu reagent. In: Methods in Enzymology. Vol 299. Oxidants and Antioxidants Part A. Academic Press; 1999:152-178. doi:10.1016/S0076-6879(99)99017-1
OECD. Test No. 423: Acute Oral Toxicity - Acute Toxic Class Method. Organization for Economic Co-operation and Development; 2002. Accessed June 15, 2023. https://www.oecd- ilibrary.org/environment/test-no-423-acute-oral-toxicity-acute-toxic-class- method_9789264071001-en
Ferreira SH. A new method for measuring variations of rat paw volume. J Pharm Pharmacol. 1979;31(9):648. doi:10.1111/j.2042-7158.1979.tb13616.x
Oliveira AM de, Nascimento MF do, Ferreira MRA, et al. Evaluation of acute toxicity, genotoxicity and inhibitory effect on acute inflammation of an ethanol extract of Morus alba L. (Moraceae) in mice. J Ethnopharmacol. 2016;194:162-168. doi:10.1016/j.jep.2016.09.004
Cavalcante da Silva G, Macário de Oliveira A, Soares de Freitas AF, Paiva PMG, Napoleão TH. Antinociceptive and Anti-Inflammatory Effects of Saline Extract and Lectin-Rich Fraction from Microgramma vacciniifolia Rhizome in Mice. Chem Biodivers. 2021;18(6):e2100125. doi:10.1002/cbdv.202100125
Stock CC, Clarke DA, Philips FS, Barclay RK. Sarcoma 180 inhibition screening data. Cancer Res. 1955;Suppl. 2:179-331
Negri LM, Spontón EA, Salgado O, Sancho A, Denoya GI. Effect of different drying conditions on volatile compounds of Canelo pepper (Drimys winteri). J Phytol. Published online September 16, 2020:56-61. doi:10.25081/jp.2020.v12.6297
Mecchi MC, Lago JHG. Chemical constituents derived from Drimys brasiliensis Miers (Winteraceae). Nat Prod Res. 2013;27(20):1927-1929. doi:10.1080/14786419.2013.782491
Bridi R, Giordano A, Peñailillo MF, Montenegro G. Antioxidant Effect of Extracts from Native Chilean Plants on the Lipoperoxidation and Protein Oxidation of Bovine Muscle. Mol Basel Switz. 2019;24(18):3264. doi:10.3390/molecules24183264
Gastaldi B, Marino G, Assef Y, Silva Sofrás FM, Catalán C a. N, González SB. Nutraceutical Properties of Herbal Infusions from Six Native Plants of Argentine Patagonia. Plant Foods Hum Nutr Dordr Neth. 2018;73(3):180-188. doi:10.1007/s11130-018-0680-3
Maleki SJ, Crespo JF, Cabanillas B. Anti-inflammatory effects of flavonoids. Food Chem. 2019;299:125124. doi:10.1016/j.foodchem.2019.125124.
Witaicenis A, Roldão EF, Seito LN, Rocha NP, Di Stasi LC. Pharmacological and toxicological studies of Drimys angustifolia Miers. (Winteraceae). J Ethnopharmacol. 2007;111(3):541-546. doi:10.1016/j.jep.2006.12.025
Fratoni E, de Athayde AE, da Silva Machado M, et al. Antiproliferative and toxicological properties of drimanes obtained from Drimys brasiliensis stem barks. Biomed Pharmacother Biomedecine Pharmacother. 2018;103:1498-1506. doi:10.1016/j.biopha.2018.04.103
Gomes MRF, Schuh RS, Jacques ALB, et al. Biological assessment (antiviral and antioxidant) and acute toxicity of essential oils from Drimys angustifolia and D. brasiliensis. Rev Bras Farmacogn. 2013;23:284-290. doi:10.1590/S0102-695X2012005000142
Matos FJ de A. Plantas medicinais: guia de seleção e emprego de plantas medicinais do nordeste do Brasil; volume II. In: Plantas medicinais: guia de seleção e emprego de plantas medicinais do nordeste do Brasil; volume II; 1989:144-144. Accessed June 15, 2023. https://pesquisa.bvsalud.org/portal/resource/pt/lil-85607
Burgos V, Paz C, Saavedra K, Saavedra N, Foglio MA, Salazar LA. Drimenol, isodrimeninol and polygodial isolated from Drimys winteri reduce monocyte adhesion to stimulated human endothelial cells. Food Chem Toxicol Int J Publ Br Ind Biol Res Assoc. 2020;146:111775. doi:10.1016/j.fct.2020.111775
Yang W, Chen X, Li Y, Guo S, Wang Z, Yu X. Advances in Pharmacological Activities of Terpenoids. Nat Prod Commun. 2020;15(3):1934578X20903555. doi:10.1177/1934578X20903555
Burgos V, Paz C, Saavedra K, et al. Drimys winteri and isodrimeninol decreased foam cell formation in THP-1 derived macrophages. Food Chem Toxicol Int J Publ Br Ind Biol Res Assoc. 2020;146:111842. doi:10.1016/j.fct.2020.111842
Abu-Izneid T, Rauf A, Shariati MA, et al. Sesquiterpenes and their derivatives-natural anticancer compounds: An update. Pharmacol Res. 2020;161:105165. doi:10.1016/j.phrs.2020.105165
Russo A, Cardile V, Graziano ACE, et al. Antigrowth activity and induction of apoptosis in human melanoma cells by Drymis winteri forst extract and its active components. Chem Biol Interact. 2019;305:79-85. doi:10.1016/j.cbi.2019.03.029
Liu J, Zhang X, Cheng Y. Dendritic cell migration in inflammation and immunity. Cell Mol Immunol. 2021;18: 2461-2471. doi: doi.org/10.1038/s41423-021-00726-4
Zhao H, Wu L, Yan G, Chen Y, Zhou M, Wu Y, Li Y. Inflammation and tumor progression: signaling pathways and targeted intervention. Signal Transduct. Target. Ther. 2021;6(1):263. doi: 10.1038/s41392-021-00658-5
Mantovani A. The Inflammation - Cancer Connection. FEBS J. 2018;285(4):638-640. doi:10.1111/febs.14395
Gandhi Y, Kumar R, Grewal J, Rawat H, Mishra SK, Kumar V, Shakya SK, Jain V, Babu G, Sharma P, Singh A, Singh R, Acharya R. Advances in anti-inflammatory medicinal plants and phytochemicals in the management of arthritis: A comprehensive review. Food Chemistry Advances. 2022; 1: 100085. doi: 10.1016/j.focha.2022.100085
Chandra S, Gahlot M, Choudhary AN, Palai S, Almeida RS, Vasconcelos JEL, Santos FA V, Farias PAM, Coutinho HDM. Scientific evidences of anticancer potential of medicinal plants. Food Chemistry Advances. 2023;2: 100239. doi: 10.1016/j.focha.2023.100239
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Revista Contexto & Saúde
This work is licensed under a Creative Commons Attribution 4.0 International License.
Autores que publicam na Revista Contexto & Saúde concordam com os seguintes termos:
a) A submissão de trabalho(s) científico(s) original(is) pelos autores, na qualidade de titulares do direito de autor do(s) texto(s) enviado(s) ao periódico, nos termos da Lei 9.610/98, implica na cessão de direitos autorais de publicação na Revista Contexto e Saúde do(s) artigo(s) aceitos para publicação à Universidade Regional do Noroeste do Estado do Rio Grande do Sul, autorizando-se, ainda, que o(s) trabalho(s) científico(s) aprovado(s) seja(m) divulgado(s) gratuitamente, sem qualquer tipo de ressarcimento a título de direitos autorais, por meio do site da revista e suas bases de dados de indexação e repositórios, para fins de leitura, impressão e/ou download do arquivo do texto, a partir da data de aceitação para fins de publicação. Isto significa que, ao procederem a submissão do(s) artigo(s) à Revista Contexto e Saúde e, por conseguinte, a cessão gratuita dos direitos autorais relacionados ao trabalho científico enviado, os autores têm plena ciência de que não serão remunerados pela publicação do(s) artigo(s) no periódico.
b). Autores mantém os direitos autorais e concedem à revista o direito de primeira publicação, com o trabalho simultaneamente licenciado sob a Licença Creative Commons Attribution que permite o compartilhamento do trabalho com reconhecimento da autoria e publicação inicial nesta revista.
c). Autores têm autorização para assumir contratos adicionais separadamente, para distribuição não-exclusiva da versão do trabalho publicada nesta revista (ex.: publicar em repositório institucional ou como capítulo de livro), com reconhecimento de autoria e publicação inicial nesta revista.
d. Autores têm permissão e são estimulados a publicar e distribuir seu trabalho online (ex.: em repositórios institucionais ou na sua página pessoal) a qualquer ponto antes ou durante o processo editorial, já que isso pode gerar alterações produtivas, bem como aumentar o impacto e a citação do trabalho publicado (Veja O Efeito do Acesso Livre).
