Advertisement

Parasitology Research

, Volume 106, Issue 4, pp 985–989 | Cite as

Trypanocidal activity and acute toxicity assessment of triterpene acids

  • Daniele da Silva Ferreira
  • Viviane Rodrigues Esperandim
  • Miriam Paula Alonso Toldo
  • Juliana Saraiva
  • Wilson Roberto Cunha
  • Sérgio de Albuquerque
Short Communication

Abstract

The present study evaluates the in vitro and in vivo trypanocidal activity of ursolic acid and oleanolic acid against the Bolivia strain of Trypanosoma cruzi. Their acute toxicity is also assessed on the basis of median lethal dose (DL50) determination and quantification of biochemical parameters. Ursolic acid is the most active compound in vitro, furnishing IC50 of 25.5 μM and displaying 77% of trypomastigote lysis at a concentration of 128 µM. In agreement with in vitro assays, the results obtained for the in vivo assay reveals that ursolic acid (at a dose of 20 mg/Kg/day) provides the most significant reduction in the number of parasites at the parasitemic peak. Results concerning the LD50 assay and the biochemical parameters evaluated in the present study demonstrate that these substances can be safely used on an experimental basis.

Keywords

Ursolic Acid Oleanolic Acid Trypanosoma Cruzi Median Lethal Dose Triterpene Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgment

We would like to thank CAPES, CNPq, and FAPESP for financial support.

References

  1. Abdel-Barry JA, Al-Hakiem MHH (2000) Acute intraperitoneal and oral toxicity of the leaf glycosidic extract of Trigonella foenum-graecum in mice. J Ethnopharmacol 70:65–68CrossRefPubMedGoogle Scholar
  2. Bastos JK, Albuquerque S, Silva MLA (1999) Evaluation of trypanocidal activity of lignans isolated from the leaves of Zanthoxylum naranjillo. Planta Med 65:541–544CrossRefPubMedGoogle Scholar
  3. Bishop ML, Duben-Engelkirk JL, Fody EP (2000) Clinical chemistry. Philadelphia, LippincottGoogle Scholar
  4. Brener Z (1962) Therapeutic activity an criterion of cure on mice experimentally infected with Trypanosoma cruzi. Rev Inst Med Trop São Paulo 4:389–396PubMedGoogle Scholar
  5. Chiari E, Oliveira AB, Prado MA, Alves RJ, Galvao L, Araujo FG (1996) Potential use of WR6026 as prophylaxis against transfusion- transmitted American trypanosomiasis. Antimicrob Agents Chemother 40:613–615PubMedGoogle Scholar
  6. Cunha WR, Crevelin EJ, Arantes GM, Crotti AE, Silva MLA, Furtado NA, Ferreira DS (2006) A study of trypanocidal activity of triterpene acids isolated from Miconia species. Phytother Res 20:474–478CrossRefPubMedGoogle Scholar
  7. Cunha LCS, Silva MLA, Furtado NAJC, Vinhólis AHC, Martins CHG, Da Silva Filho AA, Cunha WR (2007) Antibacterial activity of triterpene acids and semi-synthetic derivatives against oral pathogens. Z Naturforsch C 62:668–672PubMedGoogle Scholar
  8. Cunha WR, Silva MLA, Dos Santos FM, Montenegro IM, Oliveira ARA, Tavares HR, Leme dos Santos HS, Da Silva JCB (2008) In vitro inhibition of tumor cell growth by Miconia fallax. Pharm Biol 46:292–294CrossRefGoogle Scholar
  9. Funayama GK, Prado Júnior JC (1974) Estudos dos caracteres de uma amostra boliviana do Trypanosoma cruzi. Rev Soc Bras Méd Trop 8:75–81Google Scholar
  10. Jannin J, Villa L (2007) An overview of Chagas disease treatment. Mem Inst Oswaldo Cruz 102:95–97CrossRefPubMedGoogle Scholar
  11. Leite JPV, Oliveira AB, Lombardi JA, Filho JDS, Chiari E (2006) Trypanocidal acitvity of triterpnes from Arrabidaea triplinervia and derivatives. Biol Pharm Bull 29:2307–2309CrossRefPubMedGoogle Scholar
  12. Lim SW, Hong SP, Jeong SW, Kim B, Bak H, Ryoo HC, Lee SH, Ahn SK (2007) Simultaneous effect of ursolic acid and oleanolic acid on epidermal permeability barrier function and epidermal keratinocyte differentiation via peroxisome proliferator-activated receptor-α. J Dermatol 34:625–634CrossRefPubMedGoogle Scholar
  13. Litchfield JT, Wilcoxon F (1949) A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther 96:99–113PubMedGoogle Scholar
  14. Liu J (1995) Pharmacology of oleanoic acid and ursolic acid. J Ethnopharmacol 49:57–68CrossRefPubMedGoogle Scholar
  15. Martin-Aragón S, De Las HB, Sanchez-Reus MI, Benedi J (2001) Pharmacological modification of endogenous antioxidant enzymes by ursolic acid on tetrachloride-induced liver damage in rats and primary cultures of rat hepatocytes. Exp Toxicol Pathol 53:199–206CrossRefPubMedGoogle Scholar
  16. Martinez-Díaz RA, Escario JÁ, Nogal-Ruiz JJ, Gómez-Barrio A (2001) Relationship between biologicaI behaviour and randomly amplified polymorphic DNA profiles of Trypanosoma cruzi strains. Mem Inst Oswaldo Cruz 96:251–256PubMedGoogle Scholar
  17. Mckerrow JH, Doyle PS, Engel JC, Robertson SA, Ferreira R, Saxton T, Arkim M, Kerr ID, Brinen LS, Craik CS (2009) Two approaches to discovering and developing new drugs for Chagas disease. Mem Inst Oswaldo Cruz 104:263–269CrossRefPubMedGoogle Scholar
  18. Mizushina Y, Ikuta A, Endoh K, Oshige M, Kasai N, Kamiya K, Satake T, Takazawa H, Morita H, Tomiyasu H, Yoshida H, Sugawara F, Sakaguchi K (2003) Inhibition of DNA polymerases and DNA topoisomerase II by triterpenes produced by plant callus. Biochem Biophys Res Commun 305:365–373CrossRefPubMedGoogle Scholar
  19. Muelas-Serrano S, Nogal-Ruiz JJ, Gómez-Barrio A (2000) Setting of a colorimetric method to determine the viability of Trypanosoma cruzi epimastigotes. Parasitol Res 86:999–1002CrossRefPubMedGoogle Scholar
  20. Murugesan GS, Sathishkumar M, Jayabalan R, Binupriya AR, Yun SE, YUN SE (2009) Hepatoprotective and curative properties of kombucha tea against tetrachloride-induced toxicity. J Microbiol Biotechnol 19:397–402CrossRefPubMedGoogle Scholar
  21. Okudo T, Koshimizu K, Daito H, Kin B, Nishmoto K, Yamazaki N (2000) Health drinks containing ursolic acid and oleanoic acid. Chem Abst 112:757–763Google Scholar
  22. Pires OC, Taquemasa AVC, Akisue G, Oliveira F, Araújo CEP (2004) Análise preliminar da toxicidade aguda e dose letal mediana (DL50) comparativa entre os frutos de Pimenta-do-Reino do Brasil (Schinus terebinthifolius Raddi) e Pimenta do Reino (Piper nigrum L.). Acta Farm Bon 23:176–182Google Scholar
  23. Resende FA, Barcala CAMA, Faria MCS, Kato FH, Cunha WR, Tavares DC (2006) Antimutagenicity of ursolic and oleanoic acid against doxorubicin-induced clastogenesis in Balb/c mice. Life Sci 79:1268–1273CrossRefGoogle Scholar
  24. Ribeiro RD, Lopes RA, Carmo TA, Rissato TA (1988) Indice de cura de camundongos tratados com nifurtimox e benzonidazol na doença de Chagas experimental. Rev Ciênc Farm 10:71–76Google Scholar
  25. Saravan R, Viswanathan P, Pugalendi KV (2006) Protective effect of ursolic acid on ethanol-mediated experimental liver damage in rats. Life Sci 78:713–718CrossRefGoogle Scholar
  26. Singh GB, Singh S, Bani S, Gupta BD, Banerjee SK (1992) Anti-inflamatory activity of oleanoic acid in rats and mice. J Pharm Pharmacol 44:456–458PubMedGoogle Scholar
  27. Tamano S, Kurata Y, Shibata M, Tanaka H, Ogiso T, Ito N (1991) 13-Week oral toxicity study of captafol in F344/DuCrj rats. Fundam Appl Toxicol 17:390–398CrossRefPubMedGoogle Scholar
  28. Vasconcelos MAL, Royo VA, Ferreira DS, Crotti AEM, Silva MLA, Carvalho JCT, Bastos JK, Cunha WR (2006) Evaluation of the in vivo analgesic and anti- inflammatory activities of ursolic acid and oleanoic acid from Miconia albicans (Melastomataceae). Z Naturforsch C 61:477–482PubMedGoogle Scholar
  29. Visen PK, Saraswat B, Dhawan BN (1998) Curative effect of picroliv on primary cultured rat hepatocytes against different hepatotoxins: an in vitro study. J Pharmacol Toxicol Methods 40:173–179CrossRefPubMedGoogle Scholar
  30. World Health Organization, Reporte del grupo de trabajo científico sobre la enfermedad de Chagas (2005) Actualizado en julio de 2007, Buenos Aires, Argentina, Document TDR/SWG/09Google Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Daniele da Silva Ferreira
    • 1
  • Viviane Rodrigues Esperandim
    • 1
  • Miriam Paula Alonso Toldo
    • 1
  • Juliana Saraiva
    • 1
  • Wilson Roberto Cunha
    • 2
  • Sérgio de Albuquerque
    • 1
  1. 1.Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São PauloRibeirão PretoBrazil
  2. 2.Núcleo de Pesquisa em Ciências Exatas e Tecnológicas da Universidade de FrancaFrancaBrazil

Personalised recommendations