Hostname: page-component-78c5997874-dh8gc Total loading time: 0 Render date: 2024-11-07T08:34:51.443Z Has data issue: false hasContentIssue false
  • English
  • Français

Leishmanicidal effect of Spiranthera odoratíssima (Rutaceae) and its isolated alkaloid skimmianine occurs by a nitric oxide dependent mechanism

Published online by Cambridge University Press:  03 August 2011

ROGERIO ALEXANDRE NUNES DOS SANTOS ,
JOÃO BATISTA JÚNIOR ,
SUELLEN IARA GUIRRA ROSA ,
HERON FERNANDES TORQUATO ,
CARMEN LÚCIA BASSI ,
TEREZA AUXILIADORA NASCIMENTO RIBEIRO ,
PAULO TEIXEIRA DE SOUSA JÚNIOR ,
ÂNGELA MÁRCIA SELHORST E SILVA BESSERA ,
COR JESUS FERNANDES FONTES  and
LUIZ EVERSON DA SILVA
...Show all authors
ROGERIO ALEXANDRE NUNES DOS SANTOS
Affiliation:
Laboratório de Imunofarmacologia, Laboratório de Tecnologia Farmacêutica- LTF, Departamento de Fisiologia e Patologia, Universidade Federal da Paraíba – UFPB, Campus I, João Pessoa, Paraíba, Brazil Departamento de Enfermagem, Universidade do Estado de Mato Grosso – UNEMAT, Campus Tangará da Serra, Mato Grosso, Brazil Faculdade de Farmácia, Universidade de Cuiabá – UNIC, Campus Beira Rio, Cuiabá, Mato Grosso, Brazil
JOÃO BATISTA JÚNIOR
Affiliation:
Faculdade de Farmácia, Universidade de Cuiabá – UNIC, Campus Beira Rio, Cuiabá, Mato Grosso, Brazil
SUELLEN IARA GUIRRA ROSA
Affiliation:
Laboratório de Investigação Médica – LI, Faculdade de Ciências Médicas – FCM, Universidade Federal de Mato Grosso – UFMT, Cuiabá, Mato Grosso, Brazil
HERON FERNANDES TORQUATO
Affiliation:
Faculdade de Farmácia, Universidade de Cuiabá – UNIC, Campus Beira Rio, Cuiabá, Mato Grosso, Brazil
CARMEN LÚCIA BASSI
Affiliation:
Laboratório de Investigação Médica – LI, Faculdade de Ciências Médicas – FCM, Universidade Federal de Mato Grosso – UFMT, Cuiabá, Mato Grosso, Brazil
TEREZA AUXILIADORA NASCIMENTO RIBEIRO
Affiliation:
Departamento de Química, Instituto de Ciências Exatas, Universidade Federal Rural do Rio de Janeiro – UFRJ, Seropédica, Rio de Janeiro, Brazil
PAULO TEIXEIRA DE SOUSA JÚNIOR
Affiliation:
Departamento de Química, Universidade Federal de Mato Grosso – UFMT, Cuiabá Mato Grosso, Brazil
ÂNGELA MÁRCIA SELHORST E SILVA BESSERA
Affiliation:
Faculdade de Farmácia, Universidade de Cuiabá – UNIC, Campus Beira Rio, Cuiabá, Mato Grosso, Brazil
COR JESUS FERNANDES FONTES
Affiliation:
Laboratório de Investigação Médica – LI, Faculdade de Ciências Médicas – FCM, Universidade Federal de Mato Grosso – UFMT, Cuiabá, Mato Grosso, Brazil
LUIZ EVERSON DA SILVA
Affiliation:
Departamento de Química, Universidade Federal de Mato Grosso – UFMT, Cuiabá Mato Grosso, Brazil
MÁRCIA REGINA PIUVEZAM*
Affiliation:
Laboratório de Imunofarmacologia, Laboratório de Tecnologia Farmacêutica- LTF, Departamento de Fisiologia e Patologia, Universidade Federal da Paraíba – UFPB, Campus I, João Pessoa, Paraíba, Brazil
*
*Corresponding author: Laboratório de Imunofarmacologia, Laboratório de Tecnologia Farmacêutica- LTF, Departamento de Fisiologia e Patologia, Universidade Federal da Paraíba – UFPB, Campus I, João Pessoa, Paraíba, Brazil CEP 58051-900. Tel: +55(83) 3216 7003. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

Leishmaniasis is one of the neglected diseases. High cost, systemic toxicity, and diminished efficacy due to development of resistance by the parasites has a negative impact on the current treatment options. Thus, the search for a new, effective and safer anti-leishmanial drug becomes of paramount importance. Compounds derived from natural products may be a better and cheaper source in this regard. This study evaluated the in vitro anti-leishmanial activity of Spiranthera odoratíssima (Rutaceae) fractions and isolated compounds, using promastigote and amastigote forms of different Leishmania species. J774 A.1 macrophage was used as the parasite host cell for the in vitro assays. Evaluations of cytoxicity, nitric oxide (NO), interleukin-10 and in silico analysis were carried out. In vitro experiments showed that the fruit hexanic fraction (Fhf) and its alkaloid skimmianine (Skm) have a significant (P<0·001) effect against L. braziliensis. This anti-L. braziliensis activity of Fhf and Skm was due to increased production of NO and attenuation of IL-10 production in the macrophages at concentrations ranging from 1·6 to 40·0 μg/ml. The in silico assay demonstrated significant interaction between Skm and amino acid residues of NOS2. Skm is thus a promising drug candidate for L. braziliensis due to its potent immunomodulatory activity.

Keywords

Spiranthera odoratíssima (Rutaceae)leishmanicidal effectskimmianineNOS2in silico assay
Type
Research Article
Information
Parasitology , Volume 138 , Issue 10 , September 2011 , pp. 1224 - 1233
Copyright
Copyright © Cambridge University Press 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Albernaz, L. C., Elias de Paula, J., Romero, G. A. S., Silva, M. R. R., Grellier, P., Mambu, L. and Espindola, L. S. (2010). Investigation of plant extracts in traditional medicine of the Brazilian Cerrado against protozoans and yeasts. Journal of Ethnopharmacology 131, 116–121.CrossRefGoogle ScholarPubMed
Alexandre-Moreira, M. S., Freire-de-Lima, C. G., Trindade, M. N., Castro-Faria-Neto, H. C., Piuvezam, M. R. and Peçanha, L. M. T. (2003). Cissampelos sympodialis Eichl (Menispermaceae) leaf extract induces interleukin-10-dependent inhibition of Trypanossoma cruzi killing by macrophages. Brazilian Journal of Medical and Biological Research 36, 199–205.CrossRefGoogle Scholar
Al-Nasiry, S., Geusens, N., Hanssens, M., Luyten, C. and Pijnenborg, R. (2007). The use of Alamar Blue assay for quantitative analysis of viability, migration and invasion of choriocarcinoma cells. Human Reproduction 22, 1304–309.CrossRefGoogle ScholarPubMed
Barreto, R. L., Correia, C. R. D. and Muscará, M. N. (2005). Nitric oxide: properties and therapeutic use. Química Nova 28, 1046–1054. doi: 10.1590/S0100-40422005000600020.CrossRefGoogle Scholar
Bogdan, C. (2001). Nitric oxide and immune response. Nature Immunology 2, 907–916.CrossRefGoogle Scholar
Brunet, L. R. (2001). Nitric oxide in parasitic infections. International Immunopharmacology 1, 1457–1467.CrossRefGoogle ScholarPubMed
Carmo, E. V.d.S., Katz, S. and Barbiéri, C. L. (2010). Neutrophils reduce the parasite burden in Leishmania (Leishmania) amazonensis-infected macrophages. PloS one [electronic resource] 5, e13815. doi:10.1371/journal.pone.0013815.CrossRefGoogle Scholar
Chappuis, F., Sundar, S., Hailu, A., Ghalib, H., Rijal, S., Peeling, R. W., Alvar, J. and Boelaert, M. (2007). Visceral leishmaniasis: what are the needs for diagnosis, treatment and control? Nature Reviews Microbiology 5, S7–S16. doi:10.1038/nrmicro1748.CrossRefGoogle ScholarPubMed
Cruz, E. A., Da-Silva, S. A. G., Muzitano, M. F., Silva, P. M. R., Costa, S. S. and Rossi-Bergmann, B. (2008). Immunomodulatory pretreatment with Kalanchoe pinnata extract and its quercitrin flavonoid effectively protects mice against fatal anaphylactic shock. International Immunopharmacoogyl 8, 1616–1621.CrossRefGoogle ScholarPubMed
Das, B. B., Sen, N., Dasgupta, S. B., Ganguly, A., Das, R. and Majumder, H. K. (2006). Topoisomerase research of kinetoplastid parasite Leishmania, with special reference to development of therapeutics. The Indian Journal of Medical Research 123, 221–232.Google ScholarPubMed
De La Cruz, M. G. F. (1997). Plantas medicinais utilizadas por raizeiros. Uma abordagem etnobotânica no contexto da saúde e da doença. Dissertação de Mestrado, UFMT, Cuiabá.Google Scholar
Ding, A. H., Nathan, C. F. and Stuehr, D. J. (1988). Release of reactive nitrogen internediates and reactive oxygen intermediates from mouse peritoneal macrophages. Journal of Immunology 144, 2407–2412.CrossRefGoogle Scholar
Fournet, A., Munõz, A. B. C., Cavé, A. and Hocquemiller, R. (1993). Effect of some bisbenzylisoquinoline alkaloids on American Leishmania sp. in BALB/c mice. Phytoterapy Research 7, 281–284.CrossRefGoogle Scholar
Froelich, B. O., Kakooko, A., Siems, K., Schubert, C. and Jenett-Siems, K. (2007). Plants traditionally used against malaria: phytochemical and pharmacological investigation of Momordica foetida. Brazilian Journal of Pharmacognosy 17, 1–7.CrossRefGoogle Scholar
Garcin, E. D., Arvai, A. S., Rosenfeld, R. J., Kroeger, M. D., Crane, B. R., Andersson, G., Andrews, G., Hamley, P. J., Mallinder, P. R., Nicholls, D. J., St-Gallay, S. A., Tinker, A. C., Gensmantel, N. P., Mete, A., Cheshire, D. R., Connolly, S., Stuehr, D. J., Aberg, A., Wallace, A. V., Tainer, J. A. and Getzoff, E. D. (2008). Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase. Nature Chemical Biology 4, 700–707.CrossRefGoogle ScholarPubMed
Gazzinelli, R. T., Oswald, I. P., James, S. L. and Sher, A. (1992). IL-10 inhibits parasite killing and nitrogen oxide production by IFN- gamma-activated macrophages. The Journal of Immunology 148, 1792–1796.CrossRefGoogle ScholarPubMed
Ghalib, H. W., Piuvezam, M. R., Skeiky, Y. A., Siddig, M., Hashim, F. A., el-Hassan, A. M., Russo, D. M. and Reed, S. G. (1993). Interleukin 10 production correlates with pathology in human Leishmania donovani infections. The Journal of Clinical Investigation 92, 324–329.CrossRefGoogle ScholarPubMed
González, U., Pinart, M., Reveiz, L., Rengifo-Pardo, M., Tweed, J., Macaya, A. and Alvar, J. (2010). Designing and reporting clinical trials on treatments for cutaneous leishmaniasis. Clinical Infectious Diseases 51, 409–419.CrossRefGoogle ScholarPubMed
Lauw, F. N., Pajkrt, D., Hack, C. E., Kurimoto, M., Van Deventer, S. J. H. and Van der Poll, T. (2000). Proinflammatory effects of IL-10 during human endotoxemia. The Journal of Immunology 165, 2783–2789.CrossRefGoogle ScholarPubMed
Lenta, B. N., Vonthron-Sénécheau, C. R., Sohd, F., Tantangmo, F., Ngouela, S., Kaiser, M., Tsamo, E., Anton, R. and Weniger, B. (2007). In vitro antiprotozoal activities and cytotoxicity of some selected Cameroonian medicinal plants. Journal of Ethnopharmacology 111, 8–12.CrossRefGoogle Scholar
Lima, L. M. (2007). Modern medicinal chemistry: challenges and Brazilian contribution. Química Nova 30, 1456–1468. doi: 10.1590/S0100-40422007000600015.CrossRefGoogle Scholar
Matos, L. G., Pontes, I. S., Tresvenzol, L. M. F., Paula, J. R. and Costa, E. A. (2005). Analgesic and anti-inflammatory activity of the ethanolic extract from Spiranthera odoratissima A. St. Hillaire (Manacá) roots. Phytotherapy Research 18, 963–966. DOI: 10.1002/ptr.1301.CrossRefGoogle Scholar
Mishra, B. B., Singh, R. K., Srivastava, A., Tripathi, V. J. and Tiwari, V. K. (2009). Fighting against leishmaniasis: search of alkaloids as future true potential anti-leishmanial agents. Mini-Reviews in Medicinal Chemistry 9, 107–123.CrossRefGoogle ScholarPubMed
Nathan, C. (1992). Nitric oxide as a secretory product of mammalian cells. The FASEB Journal 6, 3051–3064.CrossRefGoogle ScholarPubMed
Polonio, T. and Efferth, T. (2008) Leishmaniasis: drug resistance and natural products (Review). International Journal of Molecular Medicine 22, 277–286. doi: 10.3892/ijmm_00000020.Google Scholar
Ribeiro, T. A. N., Da Silva Ndiaye, E. A., Velozo, E. S., Vieira, P. C., Ellena, J. and De Sousa Júnior, P. T. (2005). Limonoids from Spiranthera odoratíssima St. Hil. Journal of the Brazilian Chemical Society 16, 1347–1352. doi: 10.1590/S0103-50532005000800007.CrossRefGoogle Scholar
Rosa, M. S. S., Mendonça-Filho, R. R., Bizzo, H. R., Rodrigues, I. A., Soares, R. M. A., Souto-Padrón, T., Alviano, C. S. and Lopes, A. H. C. S. (2003). Antileishmanial activity of a linalool-rich essential oil from Croton cajucara. Antimicrobial Agents and Chemotherapy 47, 1895–1901. doi: 10.1128/AAC.47.6.1895-1901.2003.CrossRefGoogle Scholar
Sen, R. and Chatterjee, M. (2011). Plant derived therapeutics for the treatment of Leishmaniasis. Phytomedicine (In the Press), Corrected Proof, Available online). doi: 10.1016/j.phymed.2011.03.004.CrossRefGoogle ScholarPubMed
Sereno, D. and Lemestre, J. (1997). Use of an enzymatic micromethod to quantify amastigote stage of Leishmania amazonensis in vitro. Parasitology Research 83, 401–403.CrossRefGoogle ScholarPubMed
Shukla, A. K., Singh, B. K., Patra, S. and Dubey, V. K. (2010). Rational approaches for drug designing against leishmaniasis. Applied Biochemistry and Biotechnology 160, 2208–2218.CrossRefGoogle ScholarPubMed
Singh, N., Kumarn, R., Gupta, S., Dube, A. and Lakshmi, V. (2008). Antileishmanial activity in vitro and in vivo of constituents of sea cucumber Actinopyga lecanora. Parasitology Research 103, 351–354.CrossRefGoogle ScholarPubMed
Soares, D. C., Andrade, A. L., Delorenzi, J. C., Silva, J. R., Freire-de-Lima, L., Falcão, C. A., Pinto, A. C., Rossi-Bergmann, B. and Saraiva, E. M. (2010). Leishmanicidal activity of Himatanthus sucuuba latex against Leishmania amazonensis. Parasitology International 59, 173–177.CrossRefGoogle ScholarPubMed
Terezan, A. P., Rossi, R. A., Almeida, R. N. A., Freitas, T. G., Fernandes, J. B., Da Silva, M. F. G. F., Vieira, P. C., Bueno, O. C., Pagnocca, F. C. and Pirani, J. R. (2010). Activities of extracts and compounds from Spiranthera odoratíssima St. Hil. (Rutaceae) in leaf-cutting ants and their symbiotic fungus. Journal of the Brazilian Chemical Society 21, 882–886. doi: 10.1590/S0103-50532010000500016.CrossRefGoogle Scholar
Thomsen, R. and Christensen, M. H. (2006). MolDock: a new technique for high-accuracy molecular docking. Journal of Medicinal Chemistry 49, 3315–3321.CrossRefGoogle ScholarPubMed
Tian, R., Xu, S., Lei, X., Jin, W., Ye, M. and Zou, M. (2005). Characterization of small-molecule–biomacromolecule interactions: from simple to complex. Trends in Analytical Chemistry 24, 810–825. doi:10.1016/j.trac.2005.03.018.CrossRefGoogle Scholar
Tiuman, T. S., Ueda-Nakamura, T., Cortez, D. A. G., Filho, B. P. D., Morgado-Díaz, J. A., De Souza, W. and Nakamura, C. V. (2005). Antileishmanial activity of parthenolide, a sesquiterpene lactone isolated from Tanacetum parthenium. Antimicrobial Agents and Chemotherapy 49, 176–182.CrossRefGoogle ScholarPubMed
Waterman, P. G. (1999). The chemical systematics of alkaloids: A review emphasising the contribution of Robert Hegnauer. Biochemical Systematics and Ecology 27, 395–406. doi:10.1016/S0305-1978(98)00097-0.CrossRefGoogle Scholar