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Effectiveness of the immunomodulatory extract of Kalanchoe pinnata against murine visceral leishmaniasis

Published online by Cambridge University Press:  07 December 2009

D. C. O. GOMES
Affiliation:
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil
M. F. MUZITANO
Affiliation:
Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense, Brazil
S. S. COSTA
Affiliation:
Núcleo de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Brazil
B. ROSSI-BERGMANN*
Affiliation:
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil
*
*Corresponding author: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21.949-900 Rio de Janeiro, Brazil. Tel/Fax: +55 (21) 2260 6963. E-mail: bartira@biof.ufrj.br

Summary

Previously, we described the protective action of the immunomodulatory extract of Kalanchoe pinnata (Kp) in murine and human cutaneous leishmaniasis. In the present study, we investigated the effectiveness of Kp against visceral leishmaniasis, using the BALB/c mouse model of infection with Leishmania chagasi. Mice receiving oral daily doses of Kp (400 mg/kg) for 30 days displayed significantly reduced hepatic and splenic parasite burden, when compared with untreated animals. Protectiveness was accompanied by a reduction in parasite-specific IgG serum levels, and impaired capacity of spleen cells to produce IL-4, but not IFN-γ and nitric oxide upon antigen recall in vitro. The reference drug Pentostam (72 mg/kg) given by the intra-peritoneal route on alternate days produced an anti-leishmanial effect similar to oral Kp. Our findings show that the oral efficacy of Kp, seen previously in murine cutaneous leishmaniasis, extends also to visceral leishmaniasis caused by L. chagasi, a difficult to treat and lethal disease of man.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2009

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References

REFERENCES

Baillie, A. J., Dolan, T. F., Alexander, J. and Carter, K. C. (1989). Visceral leishmaniasis in the BALB/c mouse: sodium stibogluconate treatment during acute and chronic stages of infection. International Journal of Pharmaceutics 15, 2328.CrossRefGoogle Scholar
Belkaid, Y., Blank, R. B. and Suffia, I. (2006). Natural regulatory T cells and parasites: a common quest for host homeostasis. Immunological Reviews 212, 287300.CrossRefGoogle ScholarPubMed
Croft, S. L., Seifert, K. and Yardley, V. (2006). Current scenario of drug development for leishmaniasis. Indian Journal Medical Research 123, 399410.Google 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 Immunopharmacology 8, 16161621. doi:10.1016/j.intimp.2008.07.006.CrossRefGoogle ScholarPubMed
Da Silva, S. A. G., Costa, S. S., Mendonça, S. C. F., Silva, E. M., Moraes, V. L. G. and Rossi-Bergmann, B. (1995). Therapeutic effect of oral Kalanchoe pinnata leaf extract in murine leishmaniasis. Acta Tropica 60, 201205.CrossRefGoogle ScholarPubMed
Da Silva, S. A., Costa, S. S. and Rossi-Bergmann, B. (1999). The anti-leishmanial effect of Kalanchoe is mediated by nitric oxide intermediates. Parasitology 118, 575582. doi:10.1017/S0031182099004357.CrossRefGoogle ScholarPubMed
Demicheli, C., Ochoa, R., Silva, J. B. B., Falcão, C. A. B., Rossi-Bergmann, B., Melo, A. L., Sinisterra, R. D. and Frezard, F. (2004). Oral delivery of meglumine antimoniate using beta-cyclodextrin for the treatment of leishmaniasis. Antimicrobial Agents and Chemotherapy 48, 100103.CrossRefGoogle ScholarPubMed
Gomes, D. C. O., Pinto, E. F., Guedes, H. L. M., Melo, L. D. B., Loma, W. P., Larraga, V., Lopes, U. G. and Rossi-Bergmann, B. (2007). Intranasal delivery of naked DNA encoding the LACK antigen leads to protective immunity against visceral leishmaniasis in mice. Vaccine 25, 21682172.CrossRefGoogle ScholarPubMed
Goto, H. and Lindoso, J. A. (2004). Immunity and immunosuppression in experimental visceral leishmaniasis. Brazilian Journal of Medical Biological Research 37, 615623.CrossRefGoogle ScholarPubMed
Green, L. C., Wagner, D. A., Glogowski, J., Skipper, P. L., Wishnok, J. S. and Tannenbaum, S. R. (1982). Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Analytical Biochemistry 126, 131138.CrossRefGoogle ScholarPubMed
Kar, K. (1995). Serodiagnosis of leishmaniasis. Critical Reviews in Microbiology 21, 123152.CrossRefGoogle ScholarPubMed
Launois, P., Louis, J. A. and Milon, G. (1997). The fate and persistence of Leishmania major in mice of different genetic backgrounds: an example of exploitation of the immune system by intracellular parasites. Parasitology 115, S25S32. doi: 10.1017/S0031182097001777.CrossRefGoogle ScholarPubMed
Muzitano, M. F., Cruz, E. A., Almeida, A. P., Silva, S. A. G., Kaiser, C. R., Guette, C., Rossi-Bergmann, B. and Costa, S. S. (2006 a). Quercitrin from Kalanchoe pinnata: the first antileishmanial flavonoid glycoside. Planta Medica 72, 8183. doi: 10.1055/s-2005-873183.CrossRefGoogle ScholarPubMed
Muzitano, M. F., Tinoco, L. W., Guette, C., Kaiser, C. R., Rossi-Bergmann, B. and Costa, S. S. (2006 b). The antileishmanial activity assessment of unusual favonoids from Kalanchoe pinnata. Phytochemistry 67, 20712077. doi: 10.1016/j.phytochem.2006.06.027.CrossRefGoogle Scholar
Muzitano, M. F., Falcão, C. A., Cruz, E. A., Bergonzi, M. C., Bilia, A. R., Vincieri, F. F., Rossi-Bergmann, B. and Costa, S. S. (2009). Oral metabolism and efficacy of Kalanchoe pinnata flavonoids in a murine model of cutaneous leishmaniasis. Planta Medica 75, 307311. doi: 10.1055/s-0028-1088382.CrossRefGoogle Scholar
Perez-Victoria, F. J., Sanchez-Canete, M. P., Seifert, K., Croft, S. L., Sundar, S., Castanys, S., and Gamarro, F. (2006). Mechanisms of experimental resistance of Leishmania to miltefosine: Implications for clinical use. Drug Resistance Updates 9, 2639.CrossRefGoogle ScholarPubMed
Rossi-Bergmann, B., Costa, S. S., Borges, M. B. S., Da Silva, S. A. G., Noleto, G. R., Souza, M. L. M. and Moraes, V. L. G. (1994). Immunosuppressive effect of the aqueous extract of Kalanchoe pinnata in mice. Phytotherapy Research 8, 399402.CrossRefGoogle Scholar
Sen, G., Mandal, S., Saha, ROY S., Mukhopadhyay, S. and Biswas, T. (2005). Therapeutic use of quercetin in the control of infection and anemia associated with visceral leishmaniasis. Free Radical Biology and Medicine 38, 12571264.CrossRefGoogle ScholarPubMed
Sen, G., Mukhopadhyay, S., Ray, M., and Biswas, T. (2008). Quercetin interferes with iron metabolism in Leishmania donovani and targets ribonucleotide reductase to exert leishmanicidal activity. Journal of Antimicrobial Chemotherapy 61, 10661075.CrossRefGoogle ScholarPubMed
Smith, A. C., Yardley, V., Rhodes, J. and Croft, S. L. (2000). Activity of the novel immunomodulatory compound Tucaresol against experimental visceral leishmaniasis. Antimicrobial Agents and Chemotherapy 44, 14941498.CrossRefGoogle ScholarPubMed
Sundar, S. (2001). Drug resistance in Indian visceral leishmaniasis. Tropical Medicine & International Health 6, 849854.CrossRefGoogle ScholarPubMed
Taylor-Robinson, A. W. (1997). Counter-regulation of T helper 1 cell proliferation by nitric oxide and interleukin-2. Biochemical Biophysical Research Communications 233, 1419.CrossRefGoogle ScholarPubMed
Torres-Santos, E. C., Da Silva, S. A. G., Costa, S. S., Santos, A. P. P. T., Almeida, A. P. and Rossi-Bergmann, B. (2003). Toxicological analysis and effectiveness of oral Kalanchoe pinnata on a human case of cutaneous leishmaniasis. Phytotherapy Research 17, 801803.CrossRefGoogle ScholarPubMed
VanWyk, B. E. and Wink, M. (2004). Medicinal Plants of the World. 1st Edn.Timber Press, Portland, Oregon, USA.Google Scholar
Vouldoukis, I., Bécherel, P. A., Riveros-Moreno, V., Arock, M., da Silva, O., Debré, P., Mazier, D. and Mossalayi, M. D. (1997). Interleukin-10 and interleukin-4 inhibit intracellular killing of Leishmania infantum and Leishmania major by human macrophages by decreasing nitric oxide generation. European Journal of Immunology 27, 860865.CrossRefGoogle ScholarPubMed
Wadhone, P., Maiti, M., Agarwal, R., Kamat, V., Martin, S. and Saha, B. (2009). Miltefosine promotes IFN-gamma-dominated anti-leishmanial immune response. Journal of Immunology 182, 71467154.CrossRefGoogle ScholarPubMed
World Health Organization (2009). Division of Control of Tropical Diseases, http://www.who.int/tdr/diseases/leish/diseaseinfo.htm (accessed in May 2009).Google Scholar
Yadav, N. P. and Dixit, V. K. (2003). Hepatoprotective activity of leaves of Kalanchoe pinnata Pers. Journal of Ethnopharmacology 86, 197202. doi: 10.1016/S0378-8741(03)00074-6.CrossRefGoogle ScholarPubMed