title: Antileishmanial activity and mechanism of action from a purified fraction of Zingiber officinalis Roscoe against Leishmania amazonensis.
abstract: In recent years, considerable attention has been given to identify new antileishmanial products derived from medicinal plants, although, to date, no new effective compound has been recently applied to treat leishmaniasis. In the present study, the antileishmanial activity of a water extract from Zingiber officinalis Roscoe (ginger) was investigated and a purified fraction, named F10, was identified as responsible by this biological activity. The chemical characterization performed for this fraction showed that it is mainly composed by flavonoids and saponins. The water extract and the F10 fraction presented IC50 values of 125.5 and 49.8 μg/mL, respectively. Their selectivity indexes (SI) were calculated and values were seven and 40 times higher, respectively, in relation to the value found for amphotericin B, which was used as a control. Additional studies were performed to evaluate the toxicity of these compounds in human red blood cells, besides of the production of nitrite, as an indicator of nitric oxide (NO), in treated and infected macrophages. The results showed that both F10 fraction and water extract were not toxic to human cells, and they were able to stimulate the nitrite production, with values of 13.6 and 5.4 μM, respectively, suggesting that their biological activity could be due to macrophages activation via NO production. In conclusion, the present study shows that a purified fraction from ginger could be evaluated in future works as a therapeutic alternative, on its own or in association with other drugs, to treat disease caused by L. amazonensis.
authors.affiliation: Programa de Pós-Graduação em Ciências da Saúde, Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Mariana C
authors.initials: MC
authors.lastname: Duarte
authors.affiliation: Laboratório de Doenças infecto-parasitárias and Programa de Pós-Graduação em Biotecnologia, Campus Centro Oeste Dona Lindu, Universidade Federal De São João Del-Rei, Divinópolis, Minas Gerais, Brazil.
authors.forename: Grasiele S V
authors.initials: GS
authors.lastname: Tavares
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Diogo G
authors.initials: DG
authors.lastname: Valadares
authors.affiliation: Programa de Pós-Graduação em Ciências da Saúde, Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Daniela P
authors.initials: DP
authors.lastname: Lage
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Tatiana G
authors.initials: TG
authors.lastname: Ribeiro
authors.affiliation: Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Letícia M R
authors.initials: LM
authors.lastname: Lage
authors.affiliation: Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Marcella R
authors.initials: MR
authors.lastname: Rodrigues
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: André A G
authors.initials: AA
authors.lastname: Faraco
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Soto
authors.affiliation: Laboratório de Doenças infecto-parasitárias and Programa de Pós-Graduação em Biotecnologia, Campus Centro Oeste Dona Lindu, Universidade Federal De São João Del-Rei, Divinópolis, Minas Gerais, Brazil.
authors.forename: Eduardo S
authors.initials: ES
authors.lastname: da Silva
authors.affiliation: Programa de Pós-Graduação em Ciências da Saúde, Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Chávez Fumagalli
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Carlos A P
authors.initials: CA
authors.lastname: Tavares
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil.
authors.forename: João Paulo V
authors.initials: JP
authors.lastname: Leite
authors.affiliation: Laboratório de Doenças infecto-parasitárias and Programa de Pós-Graduação em Biotecnologia, Campus Centro Oeste Dona Lindu, Universidade Federal De São João Del-Rei, Divinópolis, Minas Gerais, Brazil.
authors.forename: Jamil S
authors.initials: JS
authors.lastname: Oliveira
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Rachel O
authors.initials: RO
authors.lastname: Castilho
authors.affiliation: Programa de Pós-Graduação em Ciências da Saúde, Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address: eduardoferrazcoelho@yahoo.com.br.
authors.forename: Eduardo A F
authors.initials: EA
authors.lastname: Coelho
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D002850:Chromatography, Gel; D002855:Chromatography, Thin Layer; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D020939:Zingiber officinale / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D007894:Leishmania mexicana / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D027343:Rhizome / Q000737:chemistry; D013047:Specific Pathogen-Free Organisms
chemical_list: D000981:Antiprotozoal Agents; D010936:Plant Extracts; D009569:Nitric Oxide; D000666:Amphotericin B
keywords: Antileishmanial activity; Leishmania amazonensis; Nitric oxide; Purified compounds; Treatment; Zingiber officinalis Roscoe