Volume 77, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


In vitro trypanocidal and leishmanicidal activities of the flavonoids hispidulin, from , and santin, from , are reported. A sensitive technique that takes advantage of (H)thymidine uptake by dividing trypanosomatids has been adjusted for quantification of the parasiticidal effect of the natural products. The IC values for hispidulin and santin on epimastigotes were 46.7 and 47.4 μM, respectively. On trypomastigotes, the IC values were 62.3 μM for hispidulin and 42.1 μM for santin. Hispidulin was more active than santin on promastigotes of (IC = 6.0 μM versus 32.5 μM). No cytotoxic activity was observed on lymphoid cells, making hispidulin and santin potential lead compounds for the development of new natural drugs. This is the first report on the trypanocidal and leishmanicidal activities of these flavonoids and on the presence of santin in .


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Editorial, 2006. Chagas’ disease—an epidemic that can no longer be ignored. Lancet 368 : 619. [Google Scholar]
  2. World Health Organization, 2000. Leishmania/HIV co-infection. Fact sheet No. 116. Geneva: WHO.
  3. Chiaramonte MG, Zwirner NW, Caropresi SL, Heredia V, Taranto NJ, Malchiodi EL, 1996. [Human leishmaniasis infection in the Province of Salta. Evidence of mixed infection with Trypanosoma cruzi and Leishmania spp.] Medicina (B Aires) 56 : 259–268 [article in Spanish]. [Google Scholar]
  4. Chiaramonte MG, Zwirner NW, Caropresi SL, Taranto NJ, Malchiodi EL, 1996. Trypanosoma cruzi and Leishmania spp. human mixed infection. Am J Trop Med Hyg 54 : 272–273. [Google Scholar]
  5. Chiaramonte MG, Frank FM, Furer GM, Taranto NJ, Margni RA, Malchiodi EL, 1999. Polymerase chain reaction reveals Trypanosoma cruzi infection suspected by serology in cutaneous and mucocutaneous leishmaniasis patients. Acta Trop 72 : 295–308. [Google Scholar]
  6. Frank FM, Fernandez MM, Taranto NJ, Cajal SP, Margni RA, Castro E, Thomaz-Soccol V, Malchiodi EL, 2003. Characterization of human infection by Leishmania spp. in the Northwest of Argentina: immune response, double infection with Trypanosoma cruzi and species of Leishmania involved. Parasitology 126 : 31–39. [Google Scholar]
  7. Taranto NJ, Cajal SP, De Marzi MC, Fernandez MM, Frank FM, Bru AM, Minvielle MC, Basualdo JA, Malchiodi EL, 2003. Clinical status and parasitic infection in a Wichi Aboriginal community in Salta, Argentina. Trans R Soc Trop Med Hyg 97 : 554–558. [Google Scholar]
  8. Desjeux P, 2001. Worldwide increasing risk factors for leishmaniasis. Med Microbiol Immunol (Berl) 190 : 77–79. [Google Scholar]
  9. World Health Organization, 1984. The Leishmaniases. Public Health Aspects. WHO Technical Report Series 701. Geneva: WHO, 53–60.
  10. Castro JA, de Mecca MM, Bartel LC, 2006. Toxic side effects of drugs used to treat Chagas’ disease (American trypanosomiasis). Hum Exp Toxicol 25 : 471–479. [Google Scholar]
  11. Davis AJ, Murray HW, Handman E, 2004. Drugs against leishmaniasis: a synergy of technology and partnerships. Trends Parasitol 20 : 73–76. [Google Scholar]
  12. Troullier P, Olliaro P, Torreele E, Orbinski J, Laing R, Ford N, 2002. Drug development for neglected diseases: a deficient market and a public health policy failure. Lancet 359 : 2188–2194. [Google Scholar]
  13. Sülsen V, Güida C, Coussio J, Paveto C, Muschietti L, Martino V, 2006. In vitro evaluation of trypanocidal activity in plants used in Argentine traditional medicine. Parasitol Res 98 : 370–374. [Google Scholar]
  14. Hieronymus J, 1882. Plantae diaphoricae florae Argentinae. Boletín de la Academia Nacional de Ciencias en Córdoba. 4 : 345–346. [Google Scholar]
  15. Saggese D, 1959. Yerbas Medicinales Argentinas. Tenth edition. Rosario, Argentina: Antognazzi & Cia. SRL, 25.
  16. Silva G, Oberti J, Herz W, 1992. Sesquiterpene lactones and other constituents of Argentine Ambrosia species. Phytochemistry 3 : 859–861. [Google Scholar]
  17. Villafuerte C, 1984. Diccionario de Árboles, Arbustos y Yuyos en el Folklore Argentino. Buenos Aires: Plusultra, 66.
  18. Rojas Acosta N, 1905. Plantas Medicinales de Corrientes. Buenos Aires: Imp. Gadola, 28.
  19. Muschietti L, Martino V, Ferraro G, Coussio J, 1994. 5,7,5′-Trihydroxy-3,6,2′,4′-tetramethoxyflavone from Eupatorium buniifolium. Phytochemistry 36 : 1085–1086. [Google Scholar]
  20. Carreras C, Rossomando P, Giordano O, 1998. ent-Labdanes in Eupatorium buniifolium. Phytochemistry 48 : 1031–1034. [Google Scholar]
  21. Paya M, Coussio J, Ferraro G, Martino V, Hnatyszyn O, Debenedetti S, Broussalis A, Muschietti L, Silla M, Vaya E, Alcaraz M, 1996. Inhibitory effects of various extracts of Argentine species on free radical-mediated reactions and human neutrophil functions. Phytother Res 10 : 228–232. [Google Scholar]
  22. Muschietti L, Gorzalczany S, Ferraro G, Acevedo C, Martino V, 2001. Phenolic compounds with anti-inflammatory activity from Eupatorium buniifolium. Planta Med 67 : 743–744. [Google Scholar]
  23. Buckner FS, Verlinde CL, La Flamme AC, Van Voorhis WC, 1996. Efficient technique for screening drugs for activity against Trypanosoma cruzi using parasites expressing β-galactosidase. Antimicrob Agents Chemother 40 : 2592–2597. [Google Scholar]
  24. Buckner FS, Wilson AJ, 2005. Colorimetric assay for screening compounds against Leishmania amastigotes grown in macrophages. Am J Trop Med Hyg 72 : 600–605. [Google Scholar]
  25. Ashutosh, Gupta S, Ramesh, Sundar S, Goyal N, 2005. Use of Leishmania donovani field isolates expressing the luciferase reporter gene in vitro drug screening. Antimicrob Agents Chemother 49 : 3776–3783. [Google Scholar]
  26. Chiari E, Camargo EP, 1984. Culturing and cloning of T. cruzi. Morel CM, ed. Genes and Antigens of Parasites. Rio de Janeiro: Fundação Oswaldo Cruz, 23–26.
  27. Coura JR, de Castro SL, 2002. A critical review on Chagas’ disease chemotherapy. Mem Inst Oswaldo Cruz 97 : 3–24. [Google Scholar]
  28. Esteva MA, Ruiz AM, Stoka AM, 2002. Trypanosoma cruzi: methoprene is a potent agent to sterilize blood infected with trypomastigotes. Exp Parasitol 100 : 248–251. [Google Scholar]
  29. Anesini C, Genaro A, Cremaschi G, Sterin Borda L, Cazaux C, Borda E, 1996. Immunomodulatory action of Larrea divaricata Cav. Fitoterapia 4 : 329–333. [Google Scholar]
  30. Julius M, Simpson E, Herzenberg L, 1973. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol 3 : 645–649. [Google Scholar]
  31. Ferraro G, Martino V, Borrajo G, Coussio J, 1987. 5,7,3′,4-Tetrahydroxy-6-methoxyflavanone from Eupatorium subhastatum. Phytochemistry 26 : 3092–3093. [Google Scholar]
  32. Sachde K, Kulshreshlha D, 1983. Flavonoids from Dodonaea viscosa. Phytochemistry 22 : 1253–1256. [Google Scholar]
  33. Newman D, Cragg G, Snader K, 2003. Natural products as sources of new drugs over the period 1981–2002. J Nat Prod 66 : 1022–1037. [Google Scholar]
  34. Middleton E, Kandaswami C, Theoharides T, 2000. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 52 : 673–751. [Google Scholar]
  35. Hoet S, Opperdoes F, Brun R, Adjakidjé V, Quetin-Leclercq J, 2004. In vitro antitrypanosomal activity of ethnopharmacologically selected Beninese plants. J Ethnopharmacol 91 : 37–42. [Google Scholar]
  36. Tasdemir D, Kaiser M, Brun R, Yardley V, Schmidt T, Tosun F, Rüedi P, 2006. Antitrypanosomal and antileishmanial activities of flavonoids and their analogues: in vitro, in vivo, structure–activity relationship, and quantitative structure–activity relationship studies. Antimicrob Agents Chemother 50 : 1352–1364. [Google Scholar]
  37. Kavvadias D, Sand P, Youdim K, Qaiser M, Rice-Evans C, Baur R, Sigel E, Rausch WD, Riederer P, Schreier P, 2004. The flavone hispidulin, a benzodiazepine receptor ligand with positive allosteric properties, traverses the blood–brain barrier and exhibits anticonvulsive effects. Br J Pharmacol 142 : 809–810. [Google Scholar]
  38. Abad M, Bermejo P, Alvarez M, Guerra J, Silvan A, Villar A, 2004. Flavonoids and a sesquiterpene lactone from Tanacetum microphyllum inhibit anti-inflammatory mediators in LPS-stimulated mouse peritoneal macrophages. Planta Med 70 : 34–38. [Google Scholar]

Data & Media loading...

  • Received : 08 Jan 2007
  • Accepted : 17 Jun 2007

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error