Immunomodulatory and toxicological evaluation of the fruit seeds from Platonia insignis, a native species from Brazilian Amazon Rainforest

Abstract

The “bacuri” (Platonia insignis Mart., Clusiaceae) is a native tropical fruit from the Brazilian Amazon and Northeast Regions. Its seeds are used to treat inflammatory diseases, diarrhea and skin problems in traditional medical practices. Regarding its widespread medicinal uses, it is important to evaluate the biological and toxicological potential of this species. This way, the aim of this study was to investigate the in vitro cytotoxic and immunomodulatory effects of the hexanic extract of P. insignis seeds, as well as its in vivo acute oral toxicity. The biological evaluation was performed by the determination of cytotoxic (MTT and hemolysis assay) and immunomodulatory (phagocytic capacity, lysosomal volume and nitrite production) activities of EHSB in murine peritoneal macrophages. In addition, the oral acute toxicity was evaluated using female Wistar rats treated with EHSB (2.0 g/kg), in accordance with the OECD 423 Guideline. The EHSB showed low toxicity for macrophages in the MTT test (CC50 value: 90.03 μg/ml), as well as for erythrocytes, which caused only 2.5% hemolysis at the highest concentration. A strong immunomodulatory activity was observed by a markedly increase of the NO production, phagocytic ability and lysosomal volume. On the other hand, it was not observed deaths or changes in the clinical and behavioral parameters in the toxicological evaluation. This manner, the present study contributes to the knowledge about the immunomodulatory and toxicological properties of the P. insignis. This may provide perspectives for the evaluation and development of effective and safe phytomedicines created from the Brazilian local biodiversity.

References

  1. Acuna, U.M., Jancovski, N., Kennelly, E.J., 2009. Polyisoprenylated benzophenones from clusiaceae: potential drugs and lead compounds. Curr. Top. Med. Chem. 9, 1560–1580.

    CAS  PubMed  Google Scholar 

  2. Agra, F.M., Silva, K.N., Basilio, I.J.L.D., Freitas, P.F., Barbosa-Filho, J.M., 2008. Survey of medicinal plants used inthe region Northeast of Brazil. Rev. Bras. Farmacogn. 18, 472–508.

    Google Scholar 

  3. Arcanjo, D.D.R., Costa-Júnior, J.S., Moura, L.H.P., Ferraz, A.B.F., Rossatto, R.R., David, J.M., Quintans-Junior, L.J., Oliveira, R.C.M., Citó, A.M.G.L., Oliveira, A.P., 2014. Garcinielliptone FC, a polyisoprenylated benzophenone from Platonia insignis Mart., promotes vasorelaxant effect on rat mesenteric artery. Nat. Prod. Res. 28, 923–927.

    CAS  PubMed  Google Scholar 

  4. Bentes, M.H., Serruya, H., Rocha Filho, G.N., Godoy, R.L.O., Cabral, J.A.S., Maia, J.G., 1986/1987. Estudo químico das sementes de bacuri. Acta Amaz. 16-17, 363–368.

    Google Scholar 

  5. Beutier, B., 2004. Innate immunity: an overview. Mol. Immunol. 40, 845–859.

    Google Scholar 

  6. Bonatto, S.J.R., Folador, A., Aikawa, J., Yamazaki, R.K., Pizatto, N., Oliveira, H.H.P., Vecchi, R., Calder, P.C., Fernandes, L.C., 2004. Lifelong exposure to dietary fish oil alters macrophage responses in Walker 256 tumor-bearing rats. Cell. Immunol. 231, 56–62.

    CAS  PubMed  Google Scholar 

  7. Butler, M.S., 2004. The role of natural product chemistry in drug discovery. J. Nat. Prod. 67, 2141–2153.

    CAS  PubMed  Google Scholar 

  8. Costa-Júnior, J.S., (PhD thesis) 2011. Análise Fitoquímicae Toxicológica das Sementes de Platonia insignis Mart. (Bacuri). Canoas. Graduate Program in Genetics and Applied Toxicology, Universidade Luterana do Brasil, 217 pp.

    Google Scholar 

  9. Costa-Júnior, J.S., Almeida, A.A., Costa, J.P., Citó, A.M.G.L., Saffi, J., Freitas, R.M., 2012. Superoxide dismutase and catalase activities in rat hippocampus pretreated with garcinielliptone FC from Platonia insignis. Pharm. Biol. 50, 453–457.

    PubMed  Google Scholar 

  10. Costa-Júnior, J.S., Almeida, A.A., Ferraz, A.B.F., Rossatto, R.R., Silva, T.G., Silva, P.B., Militão, G.C., Citó, A.M.G.L., Santana, L.C.L.R., Carvalho, F.A.A., Freitas, R.M., 2013b. Cytotoxic and leishmanicidal properties of garcinielliptone FC, a prenylated benzophenone from Platonia insignis. Nat. Prod. Res. 27, 470–474.

    PubMed  Google Scholar 

  11. Costa-Júnior, J.S., Feitosa, C.M., Citó, A.M.G.L., Freitas, R.M., Henriques, J.A.P., Saffi, J., 2010. Evaluation of effects of ethanolic extract from Platonia insignis Mart, on pilocarpine-induced seizures. J. Biol. Sci. (Faisalabad). 10, 747–753.

    Google Scholar 

  12. Costa-Júnior, J.S., Ferraz, A.B.F., Filho, B.A.B., Feitosa, C.M., Citó, A.M.G.L., Freitas, R.M., Saffi, J., 2011. Evaluation of antioxidant effects in vitro of garcinielliptone FC (GFC) isolated from Platonia insignis Mart. J. Med. Plants Res. 52, 293–299.

    Google Scholar 

  13. Costa-Júnior, J.S., Ferraz, A.B.F., Sousa, T.O., Silva, R.A.C., Lima, S.G., Feitosa, C.M., Citó, A.M.G.L., Cavalcante, A.A.C.M., Freitas, R.M., Sperotto, A.R.M., Péres, V.F., Moura, D.J., Saffi, J., 2013a. Investigation of biological activities of dichloromethane and ethyl acetate fractions of Platonia insignis Mart. Seed. Basic Clin. Pharmacol. Toxicol. 112, 34–41.

    PubMed  Google Scholar 

  14. Costa-Lotufo, L.V., Cunha, G.M.A., Farias, P.A.M., Viana, G.S.B., Cunha, K.M.A., 2002. The cytotoxic and embryotoxic effects of Kaurenoic acid, a diterpene isolated from Copaifera langsdorffi oleo-resin. Toxicon 40, 1231–1234.

    CAS  PubMed  Google Scholar 

  15. Diderot, N.T., Silvere, N., Etienne, T., 2006. Xanthones as therapeutic agents; chemistry and pharmacology. In: Khan, M.T.H., Ather, A. (Eds.), Advances in Phytomedicine. Leads molecules from natural products, vol. 2. Elsevier B.V, pp. 273–298.

    CAS  Google Scholar 

  16. Elias, P.M., Williams, M.L., Maloney, M.E., Bonifas, J.A., Brown, B.E., Grayson, S., Espstein, E.H., 1984. Stratum corneum lipids in disorders of cornification: steroid sulfatase and cholesterol sulfate in normal desquamation and the pathogenesis of recessive x-linked ichthyosis. J. Clin. Invest. 74, 1414–1421.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Ferreira, M.S.G., (PhD thesis) 2008. Manejo da espécie Platonía insignis Mart-Bacurizeiro, em florestas secundárias da Amazônia Oriental: proposta para uma produção sustentável. Brasília. Center of Sustainable Development, Universidade de Brasilia, 246 pp.

    Google Scholar 

  18. Genestra, M., Echevarria, A., Cysne-Finkelstein, L., Vignólio-Alves, L., Leon, L.L., 2003. Effect of amidine derivatives on nitric oxide production by Leishmania amazo-nensis promastigotes and axenic amastigotes. Nitric Oxide 8, 1–6.

    CAS  PubMed  Google Scholar 

  19. Ghazanfari, T., Hassan, Z.M., Khamesipour, A., 2006. Enhancement of peritoneal macrophage phagocytic activity against Leishmania major by garlic (Allium sativum) treatment. J. Ethnopharmacol. 103, 333–337.

    PubMed  Google Scholar 

  20. Ielpo, M.T., Basile, A., Miranda, R., Moscatiello, V., Nappo, C., Sorbo, S., Laghi, E., Ricciardi, M.M., 2000. Immunopharmacological properties of flavonoids. Fitoterapia 71, 101–109.

    Google Scholar 

  21. Krishnatry, A.S., Brazeau, D.A., Fung, H., 2010. Broad regulation of matrix and adhesion molecules in THP-1 human macrophages by nitroglycerin. Nitric Oxide 22, 11–17.

    CAS  PubMed  Google Scholar 

  22. Kumar, S., Sharma, S., Chattopadhyay, S.K., 2013. The potential health bene fit of polyisoprenylated benzophenones from Garcinia and related genera: ethnobotanical and therapeutic importance. Fitoterapia 89, 86–125.

    CAS  PubMed  Google Scholar 

  23. Lexis, L.A., Fassett, R.G., Coombes, J.S., 2006. α-Tocopherol and a-lipoic acid enhance the erythrocyte antioxidant defence in cyclosporine A-tréated rats. Basic Clin. Pharmacol. Toxicol. 98, 68–73.

    CAS  PubMed  Google Scholar 

  24. Lima, M.M.O., Vieira, L.F., Costa-Júnior, J.S., 2007. Avaliação da atividade antioxi-dante de Platonia insignis Mart (Clusiaceae). In: 2nd Congress of Research and Innovation Network Northeast Technology Education, Joao Pessoa, Brazil.

    Google Scholar 

  25. Löfgren, S.E., Miletti, L.C., Steindel, M., Bachère, E., Barracco, M.A., 2008. Trypanocidal and leishmanicidal activities of different antimicrobial peptides (AMPs) isolated from aquatic animals. Exp. Parasitol. 118, 197–202.

    PubMed  Google Scholar 

  26. Macmicking, J., Qiao-Wen, X., Nathan, C., 1997. Nitric oxide and macrophage function. Annu. Rev. Immunol. 15, 323–350.

    CAS  PubMed  Google Scholar 

  27. Moraes, L.R.B., Gutjahr, E., 2009. Química de Oleogenosas: Valorização da Biodiver-sidade Amazônica Brasília. German Technical Cooperation Agency.

    Google Scholar 

  28. Mossmann, T., 1983. Rapid colorimetric assay for cellulargrowth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55–63.

    Google Scholar 

  29. OECD, 2000. Guidance Document on the Recognition, Assessment and Use of Clinical Signs as Humane Endpoints for Experimental Animals Used in Safety Evaluation. Environmental Health and Safety Monograph Series on Testing and Assessment no. 19, http://www.oecd.org/officialdocuments/ publicdisplaydocumentpdf/?cote=env/jm/mono%282000%297&doclanguage= en (accessed December 2014).

    Google Scholar 

  30. OECD, 2001. Organization for Economic Cooperation and Development (OECD) Guidelines For Testing of Chemicals, no. 423. Acute Oral Toxic. Acute Toxic Class Method, https://doi.org/10.1787/9789264071001-en (accessed December 2014).

    Google Scholar 

  31. Reilly, T.P., Belleuve III, F.H., Woster, P.M., Svensson, C.K., 1998. Comparison of the in vitro cytotoxicity of hydroxylamine metabolites of sulfamethoxazole and dapsone. Biochem. Pharmacol. 55, 803–810.

    CAS  PubMed  Google Scholar 

  32. Rosa, R.L., Nardi, G.M., Januario, A.G.F., Bocois, R., Bagatini, K.P., Bonatto, S.J.R., Pinto, A.O., Ferreira, J.R.N., Mariano, L.N.B., Niero, R., Iagher, F., 2014. Antiinflammatory, analgesic, and immunostimulatory effects of Luehea divaricata Mart & Zucc. (Malvaceae) bark. Braz. J. Pharm. Sci. 50, 599–610.

    CAS  Google Scholar 

  33. Rufino, M.S.M., Alves, R.E.A., Brito, E.S., Pérez-Jiménez, J., Calixto-Saura, F., Mancini-Filho, J., 2010. Bioactive compounds and antioxidant capacities of 18 non-traditional tropical fruits from Brazil. Food Chem. 121, 996–1002.

    CAS  Google Scholar 

  34. Santos, M.R.V., Souza, V.H., Menezes, I.A.C., Bitencourt, J.L., Rezende-Neto, J.M., Barreto, A.S., Cunha, F.A., Marcal, R.M., Teixeira-Silva, F., Quintans-Junior, L.J., Barbosa, A.P.O., 2010. Biochemical, physiological and morphological studies of rats (Rattus norvegicus Wistar strain) produced by the Central Animal Facility of the Federal University of Sergipe. Sci. Plena. 6, 1–6.

    Google Scholar 

  35. Santos Júnior, R.Q., Soares, L.C., Maia-Filho, A.L.M., Araújo, K.S., Santos, I.M.S.P., Costa-Júnior, J.S., Saffi, J., 2010. Estudo histológico da cicatrização de feridas cutâneas utilizando a banha de bacuri (Platonia insignis Mart.). ConScientiae Saúde 9, 575–581.

    Google Scholar 

  36. Schwartz, C., (Master’s dissertation) 2007. A lecitina vegetal KM+ induz a ativação de Neutrófilos humanos com consequente aumento na capacidade fagocítica e microbicida. Curitiba. Programa de Pós-graduação em Ciências da Saúde, Pon-tifícia Universidade Católica do Paraná, 85 pp.

    Google Scholar 

  37. Serafini, M.R., Lima, C.M., Santos, R.C., Dória, G.A.A., Jesus, J.Y., Melo, M.G.D., Santos, J.P.A., Rabelo, T.K., Fortes, V.S., Fonseca, M.J.V., Albuquerque-Júnior, R.L.C., Quintans-Júnior, L.J., Araújo, A.A.S., 2011. Preclinical toxicity of Morinda citri-folia Linn. Leaf extract. Afr. J. Biotechnol. 10, 14566–14572.

    CAS  Google Scholar 

  38. Shah, A.S., Juvekar, A.R., 2010. In vitro and in vivo immunostimulatory activity of Woodfordia fruticosa flowers on non-specific immunity. Pharm. Biol. 48, 1066–1072.

    PubMed  Google Scholar 

  39. Shanley, P., Medina, G., 2005. Frutíferas e plantas úteis na vida amazônica. CIFOR, Imazon, Belém.

    Google Scholar 

  40. Silva, A.P.S.C.L., Lopes, J.S.L., Vieira, P.S., Pinheiro, E.E.A., Silva, M.L.G., Silva-Filho, J.C.C.L., Costa-Júnior, J.S., David, J.M., Freitas, R.M., 2014. Behavioral and neurochemical studies in mice pretreated with garcinielliptone FC in pilocarpine-induced seizures. Pharmacol. Biochem. Behav. 124, 305–310.

    PubMed  Google Scholar 

  41. Wagner, H., Proksch, A., 1985. Immunostimulatory drugs of fungi and higher plants. In: Wagner, H., Hikino, H., Farnsworth, N.R. (Eds.), Economic and Medicinal Plant Research, vol. I. Academic Press, London, pp. 113-153.

  42. Wagner, H., Kraus, S., Jurcic, It, 1999. Search for potent immunostimulating agents from plants and other natural sources. In: Wagner, H. (Ed.), Immunomodulatory Agents of Plants. Birkhauser, Berlin, pp. 1–39.

    Google Scholar 

  43. Wei, W.C., Su, Y.H., Chen, S.S., Sheu, J.H., Yang, N.S., 2011. GM-CSF plays a key role in zymosan-stimulated human dendritic cells for activation of Thl and Th17 cells. Cytokine 55, 79–89.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Federal University of Piauí, Fundação de Amparo à Pesquisa do Estado do Piauí, CAPES and CNPq, Brazil.

Author information

Affiliations

Authors

Contributions

AKMFL, DDRA, RGR, KAFR, FFBP, CAP and JCSF performed the experiments. DDRA, FAAM and AMGLC designed the study, supervised the laboratory work and contributed to critical reading of the manuscript. DDRA, KAFR, BQA, JSLN analyzed data. JSCJ and AMGLC contributed with reagents. DDRA and KAFR and BQA wrote the paper. DDRA revised the English proofwriting. All the authors have read the final manuscript and approved the submission.

Corresponding author

Correspondence to Antônia Maria das Graças L. Citó.

Ethics declarations

The authors declare no conflicts of interest.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Lustosa, A.K.M.F., Arcanjo, D.D.R., Ribeiro, R.G. et al. Immunomodulatory and toxicological evaluation of the fruit seeds from Platonia insignis, a native species from Brazilian Amazon Rainforest. Rev. Bras. Farmacogn. 26, 77–82 (2016). https://doi.org/10.1016/j.bjp.2015.05.014

Download citation

Keywords

  • Platonia insignis
  • Clusiaceae
  • Cytotoxic
  • Nitric oxide
  • Immunomodulatory
  • Toxicological