Bruna Taciane da Silva Bortoleti1, Fernanda Tomiotto-Pellissier2, Manoela Daiele Gonçalves3, Milena Menegazzo Miranda-Sapla4, João Paulo Assolini4, Amanda Cristina Carloto4, Débora Messagi Lima4, Guilherme Ferreira Silveira5, Ricardo Sergio Almeida6, Idessania Nazareth Costa4, Ivete Conchon-Costa4, Wander Rogério Pavanelli4. 1. Biosciences and Biotechnology Postgraduate Program, Carlos Chagas Institute, (ICC/Fiocruz/PR), Curitiba, Paraná, Brazil; State University of Londrina (UEL/PR), Laboratory of Immunoparasitology, Londrina, Paraná, Brazil. Electronic address: bruh_taciane@hotmail.com. 2. Biosciences and Biotechnology Postgraduate Program, Carlos Chagas Institute, (ICC/Fiocruz/PR), Curitiba, Paraná, Brazil; State University of Londrina (UEL/PR), Laboratory of Immunoparasitology, Londrina, Paraná, Brazil. 3. State University of Londrina (UEL/PR), Laboratory of Biotransformation and Phytochemistry, Londrina, Paraná, Brazil. 4. State University of Londrina (UEL/PR), Laboratory of Immunoparasitology, Londrina, Paraná, Brazil. 5. Carlos Chagas Institute (ICC/Fiocruz/PR), Molecular Virology Laboratory, Curitiba, Paraná, Brazil. 6. State University of Londrina (UEL/PR), Laboratory of Mycology, Londrina, Paraná, Brazil.
Abstract
BACKGROUND: Leishmaniasis is a disease caused by protozoan parasites of the Leishmania genus whose current treatment has high cost, highly toxic, and difficult administration, which makes it very important to find alternative natural compounds of high efficiency and low cost. PURPOSE: This study assessed the in vitro effect of caffeic acid (CA) on promastigotes and L. amazonensis-infected macrophages. METHODS: Evaluation of the in vitro leishmanicidal activity of CA against promastigotes and L. amazonensis infected peritoneal macrophages, as well its microbicide mechanisms. RESULTS: CA 12.5-100 µg/ml were able to inhibit promastigotes proliferation at all tested periods. The IC50, 12.5 µg/ml, also altered promastigote cell morphology and cell volume accompanied by loss of mitochondrial integrity, increase in reactive oxygen species (ROS) production, phosphatidylserine exposure, and loss of plasma membrane integrity - characterizing the apoptosis-like process. Moreover, CA reduced the percentage of infected macrophages and the number of amastigotes per macrophages increasing TNF-α, ROS, NO and reducing IL-10 levels as well as iron availability. CONCLUSION: CA showed in vitro antipromastigote and antiamostigote by increasing oxidant and inflammatory response important to eliminate the parasite.
BACKGROUND:Leishmaniasis is a disease caused by protozoan parasites of the Leishmania genus whose current treatment has high cost, highly toxic, and difficult administration, which makes it very important to find alternative natural compounds of high efficiency and low cost. PURPOSE: This study assessed the in vitro effect of caffeic acid (CA) on promastigotes and L. amazonensis-infected macrophages. METHODS: Evaluation of the in vitro leishmanicidal activity of CA against promastigotes and L. amazonensis infected peritoneal macrophages, as well its microbicide mechanisms. RESULTS: CA 12.5-100 µg/ml were able to inhibit promastigotes proliferation at all tested periods. The IC50, 12.5 µg/ml, also altered promastigote cell morphology and cell volume accompanied by loss of mitochondrial integrity, increase in reactive oxygen species (ROS) production, phosphatidylserine exposure, and loss of plasma membrane integrity - characterizing the apoptosis-like process. Moreover, CA reduced the percentage of infected macrophages and the number of amastigotes per macrophages increasing TNF-α, ROS, NO and reducing IL-10 levels as well as iron availability. CONCLUSION: CA showed in vitro antipromastigote and antiamostigote by increasing oxidant and inflammatory response important to eliminate the parasite.
Authors: Luiza F O Gervazoni; Gabrielle B Barcellos; Taiana Ferreira-Paes; Elmo E Almeida-Amaral Journal: Front Chem Date: 2020-11-23 Impact factor: 5.221