Acute and Subchronic Toxicity Assessment of Proteins from Plumeria pudica Latex in Mice




Laticiferous proteins; Toxicological evaluation; Nontoxic; DL50.


Latex proteins extracted from Plumeria pudica (LPPp) have anti-inflammatory activity in different experimental models. Considering this relevant result, we evaluated the toxicological aspects of the treatment of mice with LPPp. Acute and subchronic toxicities were determined by daily intraperitoneal administration of 40 mg/kg of LPPp for 10 or 20 days, respectively, and were followed by behavioral, hematological, biochemical and histopathological evaluation. Results showed no significant changes in body weight and organs of animals treated with LPPp. Total and differential blood leukocyte counts of LPPp groups did not differ from controls. There was no significant difference in aspartate aminotransferase, alanine aminotransferase, creatinine and urea measurements for the group treated for 20 days. The level of glutathione in the kidney was significantly higher in animals treated with LPPp in the acute toxicity test, but no differences were observed for the subchronic evaluation. The concentration of malondialdehyde and myeloperoxidase activity in the organs did not differ from controls. Histopathological examination of kidney, spleen and liver tissue of animals treated with LPPp revealed normal structures or reversible alterations. Intraperitoneal LD50 of LPPp was higher than 2,000 mg/kg. The data obtained reveal that LPPp is nontoxic at 40 mg/kg.


Agra, M. F., França, P. F. & Barbosa-Filho, J. M. (2007). Synopsis of the plants known as medicinal and poisonous in Northeast of Brazil. Revista Brasileira de Farmacognosia, 17(1), 114-140.

Agrawal, A. A. & Konno, K. (2009). Latex: a model for understanding mechanisms, ecology and evolution plant defense against herbivory. The Annual Review of Ecology, Evolution and Systematics, 40, 311-331.

Alencar, N. M. N., Figueiredo, I. S. T., Vale, M. R.; Bitencurt, F. S., Oliveira, J. S., Ribeiro, R. A. & Ramos, M. V. (2004). Anti-inflammatory effect of the latex from Calotropis procera in three different experimental models: peritonitis, paw edema and hemorrhagic cystitis. Planta Medica, 70 (12), 1144-1149. /10.1055/s-2004-835842.

Alencar, N. M. N., Oliveira, J. S., Mesquita, R. O., Lima, M. W., Vale, M. R., Etchells, J. P., Freitas, C. D. T. & Ramos, M. V. (2006). Pro- and anti-inflammatory activities of the latex from Calotropis procera (Ait.) R.Br. are trigged by compounds fractionated by dialysis, Inflammation Research., 55, 559-564. / 0.1007/s00011-006-6025-y.

Alencar, N. M. N., Pinheiro, R. S. P.; Figueiredo, I. S. T., Luz, P. B, Freitas, L. B. N., Souza T. F. G., Carmo, L. D., Marques, L. M. & Ramos, M. V. (2015). The Preventive Effect on Ethanol-Induced Gastric Lesions of the Medicinal Plant Plumeria rubra: Involvement of the Latex Proteins in the NO/cGMP/KATP Signaling Pathway. Evidence-Based Complementary and Alternative Medicine, 2015:706782.

Arnhold, J. & Flemming, J. Humam myeloperoxidase in innate and acquired immunity. (2010). Archives of Biochemistry and Biophysics, 500 (1), 92-106.

Baghel, A. S., Mishra, C. K., Rani, A., Sasmal, D. & Nema, R. K. (2010). Antibacterial activity of Plumeria rubra Linn. plant extract. Journal of Chemical and Pharmaceutical Research, 6, 435-440.

Bailey, S. A., Zidell, R. H & Perry, R. W. (2004). Relationships Between Organ Weight and Body/ Brain Weight in the Rat: What Is this Best Analytical Endpoint? Toxicologic Pathology, 32 (4), 448-466.

Bezerra, C. F., Mota, E. F., Silva, A. C. M., Tomé, A. R., Silva, M. Z. R., Brito, D., Porfírio, C. T. M. N., Oliveira, A. C., Lima-Filho, J. V. & Ramos MV. (2017). Latex proteins from Calotropis procera: Toxicity and immunological tolerance revisited. Chemico-Biological Interactions, 274 (25), 138-149.

Bradley, P. P., Priebat, D. A., Christensen, R. D & Rothstein G. (1982). Measurement of cutaneous inflammation: estimation of neutrophil content with anenzyme marker. Journal of Investigative Dermatology, 78 (3), 206-209. 10.1111/1523-1747.ep12506462.

Brito, A. S. (1994). Manual de Ensaios Toxicológicos in vivo. São Paulo, Brasil: Ed.; UNICAMP.

Cajuday, A. L & Poscidio, L. G. (2010). Effects of Moringa oleifera Lam: (Moringaceae) on the reproduction of male mice (Mus musculus). The Journal of Medicinal Plants Research, 4(12), 1115-1121.

Chiurchiù, V. & Maccarrone, M. (2016). Bioactive lipids as modulators of immunity, inflammation and emotions. Current Opinion in Pharmacology, 29,54–62. 10.1016/j.coph.2016.06.005.

Choudhary, M., Kumar, V. & Singh, S. (2014). Phytochemical and Pharmacological activity of Genus Plumeria: An updated review. International Journal of Biomedical and Advance Research, 5, 266-271.

Christapher, P. V., Mohd, S. P., Asmawi, Z., Murugaiyah, V. (2017). Acute and subchronic toxicity studies of methanol extract of Polygonum minus leaves in Sprague Dawley rats., Regulatory Toxicology and Pharmacology, 86, 33-41. doi: 10.1016/j.yrtph.2017.02.005.

Dallegri, F. & Ottonello, L. (1997). Tissue injury in neutrophilic inflammation. Inflammation Research, 46, 382-91. 10.1007/s000110050208.

Devprakash, T. R., Gurav, S., Kumar, G. P. S. & Mani, T. T. (2012). A review of phytochemical constituents & pharmacological activity of Plumeria species. International Journal of Current Pharmaceutical Research, 4 (1), 1-6.

Dwivedi, S., Shriwas, S. & Dubey, R. (2017). Traditional phytotherapy among tribal and local villages of Madhya Pradesh, India used in the treatment of Gynecological Disorders. International Journal of Pharmaceutical and Life Sciences, 8 (11), 18.

Eaton, D. L. & Klaassen, C. D. (1996). Principles of toxicology. In Casarett & Doulls' toxicology: The basic science of poisons, 5th ed. New York: The United States of America, McGraw-Hill, 463-86.

El Badwi, S. M. A., Adam, S. E., Shigidi, M. T & Hapke, H. J. (1998). Studies on laticiferous plants: toxic effects in goats of Calotropis procera latex given by different routes of administration. Deutsche Tierarztliche Wochenschrift, 105(11), 425-427.

Fernandes, H. F., Machado, D. L., Dias, J. M., Brito, T. V., Batista, J. A., Silva, R. O., Pereira, A. C. T. C., Ferreira, G. P., Ramos, M. V., Medeiros, J. V. R., Aragão, K. S., Ribeiro, R. A., Barbosa, A. L. R. & Oliveira, J. S. (2015). Laticifer proteins from Plumeria pudica inhibit the inflammatory and nociceptive responses by decreasing the action of inflammatory mediators and pro-inflammatory cytokines., Revista Brasileira de Farmacognosia, 25(3), 269–277.

Gupta, M., Mazumder, U. K., Gomathi. P. & Selvan, V. T. (2006). Anti-inflammatory evaluation of leaves of Plumeria acuminate. BMC Complementary Medicine and Therapies, 6 (36), 1472-6882. . 10.1186/1472-6882-6-36.

Lee, C. G., Silva, C. A., Dela, C. S., Ahangari, F., Ma, B., Kang, M. J., He, C. H., Takyar, S. & Elias, J. A. (2011). Role of chitin and chitinase/chitinase-like proteins in inflammation, tissue remodeling, and injury, Annual Review of Physiology 73, 479–501.

Memariani, Z., Farzaei, M. H., Ali, A. & Momtaz S. (2020). Nutritional and bioactive characterization of unexplored food rich in phytonutrients. In Woodhead Publishing Series in Food Science, Technology and Nutrition, Phytonutrients in Food, Woodhead Publishing, 157-175.

Mengue, S. S., Ments, L. A. & Schenkel, E. P. (2001). Uso de plantas medicinais durante a gravidez. In: Sanseverino, MTV, Spritzel DT, Schüler-Faccini L. (Org). Manual de Teratogênese. Porto Alegre, Brasil: Ed. da Universidade/UFRGS, 423-450.

Motta, V. T. (2003). Bioquímica Clínica para o Laboratório: princípios e interpretações. (4a ed.), Robe Editorial.

OECD (Organization for Economic Cooperation and Development). (2008). Test No. 407: Repeated Dose 28-day Oral Toxicity Study in Rodents, Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris, 2008.

OECD (Organization for Economic Cooperation and Development). (2001). Test No. 423. Acute oral toxicity: acute toxic class method. Guideline for the Testing of Chemicals, Section 4, OECD Publishing, Paris, 2001.

Oliveira, J. S., Costa-Lotufo, L. V., Bezerra, D. P., Alencar, N. M. N., Marinho-Filho, J. D. B., Figueiredo, I. S. T., Moraes, M. O., Pessoa, C, Alves. A. P. N. N. & Ramos, M. V. (2010). In vivo growth inhibition of sarcoma 180 by latex proteins from Calotropis procera. Naunyn-Schmiedeberg's Archives of Pharmacology, 382 (2),139-149. 10.1007/s00210-010-0525-6.

Oliveira, N. T. & Almeida, S. S. M. (2016). Análise fitoquímica, citotóxica e antimicrobiana do extrato bruto etanólico das folhas da espécie Ambelania acida Aublet (Apocynaceae). Biota Amazônia, 6, 20-25.

Oliveira, N. V. M., Souza, B. S., Moita, L. A., Oliveira, L. E. S, Brito, F. C., Magalhães, D. V., Batista, J. A., Sousa, S. G., Brito, T. V., Sousa, F. B. M., Alves, E. H. P., Vasconcelos, D. F. P., Freitas, C. D. T., Ramos, M. V., Barbosa, A. L. R & Oliveira JS (2019). Proteins from Plumeria pudica latex exhibit protective effect in acetic acid induced colitis in mice by inhibition of pro- inflammatory mechanisms and oxidative stress. Life Sciences, 231(15), 1-8. 10.1016/j.lfs.2019.06.010.

Oliveira, L. E. S, Moita, L. A., Souza, B. S., Oliveira, N. M. V., Sales, A. C. S., Barbosa, M. S., Silva, F. D. S., Farias, A. L. C., Lopes, V. L. R., França, L. F. C., Alves, E. H. P., Freitas, C. D. T., Ramos, M. V., Vasconcelos, D. F. P. & Oliveira JS. (2021). Latex proteins from Plumeria pudica reduce ligature‐induced periodontitis in rats. Oral Diseases, 00, 1–10.

Olson, H., Betton,G., Robinson. D., Monro, A., Kolaja, G., Lilly, P., Sanders, J., Sipes, G., Bracken, W., Dorato, M., Van Deun, K., Smith, P., Berger, B. & Heller, A. (2000). Concordance of the toxicity of pharmaceuticals in humans and in animals. Regulatory Toxicology and Pharmacology, 32 (1), 56-67. 10.1006/rtph.2000.1399.

Perandin, D., Maioli, M. A., Santos, P. R. S., Pereira, F. T. V., & Mingatto, F. E. (2015). Proteção do dano oxidativo hepático induzido por ferro pelo extrato aquoso da planta Plectranthus barbatus. Revista brasileira de plantas medicinais, 17(1),9-17.

Ramos, M. V., Aguiar, V. C., Melo, V. M. M., Mesquita, R. O., Silvestre, P. P., Oliveira, J. S., Oliveira, R. S. B., Macedo, N. M. R. & Alencar, N. M. N. (2007). Immunological and allergenic responses induced by latex fractions of Calotropis procera (Ait.) R. Br.Journal of Ethnopharmacology, 111 (1), 115-122. 10.1016/j.jep.2006.10.034.

Rathnavelu, V., Alitheen, N. B., Sohila, S., Kanagesan, S. & Ramesh, R. (2016). Potential role of bromelain in clinical and therapeutic applications. Biomed Rep, 5 (3), 283-288.

Rhiouani H, El-Hilaly J, Israili HZ, Lyoussi B. (2008). Acute and sub-chronic toxicity of an aqueous extract of the leaves of Herniaria glabra in rodents. Journal of Ethnopharmacology, 118 (13), 378–386.

Rosidah, M. F. Y., Sadikun, A., Ahmad. M., Gabriel, A. A. & Mohd, Z. A. (2009). Toxicology evaluation of standardized methanol extract of Gynura procumbens. Journal of Ethnopharmacology, 123, 244-249.

Sampieri, R. H., Collado, C. F. & Lucio, M. D. P. B. (2013). Metodologia de Pesquisa (5a ed.). McGraw-Hill.

Santana, L. A. B., Aragão, D. P., Araújo, T. S. L., Sousa, N. A., Souza, L. K. M., Oliveira, L. E. S., Pereira, A. C. T. C., Ferreira, G. P., Oliveira, N. V. M., Souza, B. S., Sousa, F. B. M., Ramos. M. V., Freitas, C. D. T., Medeiros, J. V. R & Oliveira, J. S. (2018). Antidiarrheal effects of water-soluble proteins from Plumeria pudica latex in mice. Biomedicine & Pharmacotherapy, 97, 1147-1154.

Sedlak, J., Lindsay, R. H. (1968). Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman´s reagent. Analytical Biochemistry, 25, 192-205.

Shinde, P. R., Patil, P. S., & Bairagi, V. A. (2014). Phytopharmacological Review of Plumeria species. Scholars Academic Journal of Pharmacy, 3,217–227.

Silveira, P. F., Bandeira, M. A. M. & Arrais, P. S. D. (2008). Farmacovigilância e reações adversas às plantas medicinais e fitoterápicos: uma realidade. Revista Brasileira de Farmacognosia, 18(4),618–626.

Subramanian, K. Sankaramourthy D., & Gunasekaran M. (2018). Chapter 18. Toxicity Studies Related to Medicinal Plants. In: Natural Products and Drug Discovery, USA, Elsevier, 491-505.

Uchiyama, M., & Mihara, M. (1978). Determination of malonedialdehyde precursor in tissues by thiobarbituric acid test. Analytical Biochemistry, 86 (1), 271-278.

Veiga-Júnior, V. F., Pinto, A. C., & Maciel, M. A. M. (2005). Plantas medicinais: cura segura? Quimíca Nova, 28(3),519-528.

Vergnolle, N. (2016). Protease inhibition as new therapeutic strategy for GI diseases. Gut, 65 (7), 1215–1224.

Welborn, C. R., Goldman, G., Peterson, J. S., Valeri, C. R., Shepro, D., & Hechtman, H. B. (1991). Pathophysiology of ischemia-reperfusion on injury: central role of the neutrophil. British Journal of Surgery, 78, 651-5.

World Health Organization (WHO). (2013). WHO traditional medicine strategy 2014–2023. WHO.




How to Cite

SOUZA, B. da S. .; OLIVEIRA, N. V. de M. .; MOITA, L. A.; OLIVEIRA, L. E. S. .; BRITO, F. C. de .; SILVA, F. R. P. da .; FRANÇA, L. F. de C. .; SOUSA, F. B. M. .; PEREIRA, A. C. T. C. .; FERREIRA, G. P.; MEDEIROS, J.-V. R.; FREITAS, C. D. T. de .; VASCONCELOS, D. F. P. .; OLIVEIRA, J. S. de. Acute and Subchronic Toxicity Assessment of Proteins from Plumeria pudica Latex in Mice. Research, Society and Development, [S. l.], v. 10, n. 6, p. e58610616174, 2021. DOI: 10.33448/rsd-v10i6.16174. Disponível em: Acesso em: 19 jun. 2024.



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