Casearia sylvestris Sw., Salicaceae, is an important medicinal plant widely used in Brazil for the treatment of various cardiovascular disorders. This species was included as of interest by Brazilian Unified Health System. Although preclinical studies described cardiovascular protective effects and apparent absence of toxicity, no studies have evaluated its carcinogenic potential. In this study, we proposed a short-term carcinogenesis evaluation of C. sylvestris in Wistar rats, aiming to check the safety of this species to use it as proposed by Brazilian Unified Health System. C. sylvestris leaves were obtained and the crude extract was prepared by maceration from methanol/water. Wistar rats were orally treated for 12 weeks with 50, 250 or 500 mg kg−1 of crude extract or vehicle. Body weight, daily morbidity and mortality were monitored. Blood and bone marrow samples were collect for micronucleus test, comet assay and tumor markers evaluation. Vital organs were removed to macro and histopathological analyses. The crude extract did not induce mutagenic and genotoxic effects and no alterations were observed in important tumor markers. Finally, no detectable signs of injury through gross pathology or histopathological examinations were observed. Our results certify the absence of the crude extract toxicity, indicating its safety, even at prolonged exposure as proposed by Brazilian Unified Health System.
Albano, M.N., da Silveira, M.R., Danielski, L.G., Florentino, D., Petronillio, F., Piovezan, A.P., 2013. Anti-inflammatory and antioxidant properties of hydroalcoholic crude extract from Casearia sylvestris Sw. (Salicaceae). J. Ethnopharmacol. 147, 612–617.
Ameni, A.Z., Latorre, O.A., Torres, L.M., Górniak, S.L., 2015. Toxicity study about a medicinal plant Casearia sylvestris: a contribution to the Brazilian Unified Health System (SUS). J. Ethnopharmacol. 175, 9–13.
Anvisa, 2011. Formulário de Fitoterápicos da Farmacopéia Brasileira, Agência Nacional de Vigilância Sanitária. Anvisa, Brasilia, pp. 1–126.
Bajpayee, M., Pandey, A.K., Parmar, D., Dhawan, A., 2005. Current status of short-term tests for evaluation of genotoxicity, mutagenicity, and carcinogenicity of environmental chemicals and NCEs. Toxicol. Mech. Methods 15, 155–180.
Brant, N.M.F., Gasparotto, F.M., Araújo, V.O., Maraschin, J.C., Ribeiro, R.C.L., Lourenço, E.L.B., Gasparotto Junior, A., 2014. Cardiovascular protective effects of Casearia sylvestris Swartz in Swiss and C57BL/6 LDLr-null mice undergoing high fat diet. J. Ethnopharmacol. 154, 419–427.
Carvalho, A.C.B., Perfeito, J.P.S., Silva, L.V.C., Ramalho, L.S., de Oliveira Marques, R.F., Silveira, D., 2011. Regulation of herbal medicines in Brazil: advances and perspectives. Bras. J. Pharm. Sci. 47, 467–474.
Cohen, S.M., Arnold, L.L.J., 2016. Critical role of toxicologic pathology in a short-term screen for carcinogenicity. Toxicol. Pathol. 29, 215–227.
Duff, M.J., 2001. Clinical uses of tumor markers: a critical review. Crit. Rev. Clin. Lab. Sci. 38, 225–262.
Ferreira, P.M., Bezerra, D.P., Silva, J.N., da Costa, M.P., Ferreira, J.R., Alencar, N.M., Figueiredo, I.S., Cavalheiro, A.J., Machado, CM., Chammas, R., Alves, A.P., Moraes, M.O., Pessoa, C., 2016. Preclinical anticancer effectiveness of a fraction from Casearia sylvestris and its component casearin X: in vivo and ex vivo methods and microscopy examinations. J. Ethnopharmacol. 186, 270–279.
Ferreira, P.M.P., Carvalho, A.F.F.U., Souza, D.F., Magalhães, J.F., Martins, A.R., Martins, M.A.C., Queiroz, M.G.R., 2007. Water extract of Moringa oleifera seeds: a toxicological approach. REPM 1, 45–57.
Ferreira, P.M.P., Costa-Lotufo, L.V., Moraes, M.O., Barros, F.W.A., Martins, A.M.A., Cavalheiro, A.J., Bolzani, V.S., Santos, A.G., Pessoa, C., 2011. Folk uses and pharmacological properties of Casearia sylvestris: a medicinal review. An. Acad. Bras. Cienc. 83, 1373–1384.
OECD, 1997. Guideline 474: mammalian erythrocyte micronucleus test. In: OECD (Ed.), Guideline for Testing of Chemicals. Organization for Economic Cooperation and Development, Paris, pp. 1–10.
OECD, 2014. Guideline 489: in vivo mammalian alkaline comet assay. In: OECD (Ed.), Guideline for Testing of Chemicals. Organization for Economic Co-Operation and Development, Paris, pp. 1–25.
Sauzay, C., Petit, A., Bourgeois, A.M., Barbare, J.C., Chauffert, B., Galmiche, A., Houessinon, A., 2016. Alpha-foetoprotein (AFP): a multi-purpose marker in hepatocellular carcinoma. Clin. Chim. Acta 463, 39–44.
Schoenfelder, T., Pich, CT., Geremias, R., Avila, S., Daminelli, E.N., Pedrosa, R.C., Bettiol, J., 2008. Antihyperlipidemic effect of Casearia sylvestris methanolic extract. Fitoterapia 79, 465–467.
Sponchiado, G., Adam, M.L., Silva, CD., Soley, B.S., de Mello-Sampayo, C., Cabrini, DA, Correr, C.J., Otuki, M.F., 2016. Quantitative genotoxicity assays for analysis of medicinal plants: a systematic review. J. Ethnopharmacol. 178, 289–296.
Tafazoli, S., Vo, T.D., Petersen, A., Constable, A., Coulet, M., Phothirath, P., Lang.J., Baldwin, N., 2017. Genotoxicity,acute and subchronic toxicity evaluation of savory food ingredients. Regul. Toxicol. Pharmacol. 87, 71–87.
Torres, R.B., Yamamoto, K., 1986. Taxonomia das espécies de Casearia Jacq. (Flacour-tiaceae) do estado de São Paulo. Rev. Bras. Bot. 9, 239–258.
Touitou, Y., Bogdan, A., 1998. Tumor marker in non malignant diseases. Eur. J. Cancer Clin. Oncol. 24, 1083–1091.
Varanda, E.A., 2006. Atividade mutagênica de plantas medicinais. Rev. Ciênc. Farm. Básica Apl. 27, 1–7.
WHO, 2011. The World Medicines Situation 2011: Traditional Medicines: Global Situation, Issues and Challenges. World Health Organization, Geneva, pp. 1–12.
CAST: in vivo experiments and data analyses. ELCJ: LC-MS analyses. SDVN, RDFJ and TCP: in vivo experiments. JAS, GKT and SAO: mutagenicity analyses. ACS and RICS: histopathological analyses. FARL: data analysis, data discussion and manuscript preparation. AGJ: data discussion and manuscript correction.
Conflicts of interest
The authors declare no conflicts of interest.
About this article
Cite this article
Tirloni, C.A.S., Traesel, G.K., Lívero, F.A.R. et al. Short-term carcinogenesis evaluation of Casearia sylvestris. Rev. Bras. Farmacogn. 27, 603–610 (2017). https://doi.org/10.1016/j.bjp.2017.05.009
- Short-term carcinogenesis
- Tumor markers