title: Stachytarpheta cayennensis extract inhibits promastigote and amastigote growth in Leishmania amazonensis via parasite arginase inhibition.
abstract: BACKGROUND
  Stachytarpheta cayennensis is a plant that is traditionally used to treat tegumentary leishmaniasis and as an anti-inflammatory agent.
  
  
  OBJECTIVE
  This study aimed to evaluate the action of S. cayennensis extracts on the Leishmania (Leishmania) amazonensis arginase enzyme.
  
  
  METHODS
  S. cayennensis was collected from the Brazilian Amazon region. Aqueous extracts were fractionated with n-butanol. The leishmanicidal effects of the n-butanolic fraction (BUF) were evaluated in L. (L.) amazonensis promastigotes and amastigotes. BUF was tested against recombinant arginase from both L. (L.) amazonensis and macrophage arginase. Promastigote cultures and infected macrophage cultures were supplemented with L-ornithine to verify arginase inhibition. NMR analysis was used to identify the major components of BUF.
  
  
  RESULTS
  BUF showed an EC50of 51 and 32µg/mL against promastigotes and amastigotes of L. (L.) amazonensis, respectively. BUF contains a mixture of verbascoside and isoverbascoside (7:3 ratio) and is a potent L. (L.) amazonensis arginase inhibitor (IC50=1.2µg/mL), while macrophage arginase was weakly inhibited (IC50>1000µg/mL). The inhibition of arginase by BUF in promastigotes and amastigotes could be demonstrated by culture media supplementation with L-ornithine, a product of the hydrolysis of L-arginine by arginase.
  
  
  CONCLUSIONS
  Leishmanicidal effects of the S. cayennensis BUF fraction on L. (L.) amazonensis are associated with selective parasite arginase inhibition.
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, Rod. Washington Luís, Km 235, 13565-905 São Carlos, SP, Brazil. Electronic address: cmaquiaveli@usp.br.
authors.forename: Claudia do Carmo
authors.initials: CDC
authors.lastname: Maquiaveli
authors.affiliation: Departamento de Medicina Veterinária, Universidade de São Paulo, Av. Duque de Caxias Norte, 225, 13635-900 Pirassununga, SP, Brazil.
authors.forename: Amanda Maria
authors.initials: AM
authors.lastname: Oliveira E Sá
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, Rod. Washington Luís, Km 235, 13565-905 São Carlos, SP, Brazil.
authors.forename: Paulo Cezar
authors.initials: PC
authors.lastname: Vieira
authors.affiliation: Departamento de Medicina Veterinária, Universidade de São Paulo, Av. Duque de Caxias Norte, 225, 13635-900 Pirassununga, SP, Brazil. Electronic address: edsilva@usp.br.
authors.forename: Edson Roberto
authors.initials: ER
authors.lastname: da Silva
mesh_terms: D020001:1-Butanol / Q000737:chemistry; D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D007891:Leishmania / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000469:parasitology; D051379:Mice; D009952:Ornithine / Q000494:pharmacology; D021261:Parasitic Sensitivity Tests; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000067996:RAW 264.7 Cells; D012997:Solvents / Q000737:chemistry; D014344:Trypanocidal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D029648:Verbenaceae / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D010936:Plant Extracts; D015800:Protozoan Proteins; D012997:Solvents; D014344:Trypanocidal Agents; D020001:1-Butanol; D009952:Ornithine; D001119:Arginase
keywords: Arginase; Isoverbascoside; Leishmania; Polyamines; Stachytarpheta cayennensis; Verbascoside