Leishmanicidal and immunomodulatory activity of Terminalia catappa in Leishmania amazonensis in vitro infection
Sandra Alves de Araújo,
Carla Maria Pereira Silva,
Carolina Silva Costa,
Clarissa Sousa Costa Ferreira,
Helen Silva Ribeiro,
Aldilene da Silva Lima,
Cláudia Quintino da Rocha,
Kátia da Silva Calabrese,
Ana Lucia Abreu-Silva,
Fernando Almeida-Souza
Affiliations
Sandra Alves de Araújo
Rede Nordeste de Biotecnologia, Universidade Federal do Maranhão, São Luís, 65080-805, Brazil
Carla Maria Pereira Silva
Universidade Estadual do Maranhão, São Luís, 65055-310, Brazil
Carolina Silva Costa
Universidade Estadual do Maranhão, São Luís, 65055-310, Brazil
Clarissa Sousa Costa Ferreira
Universidade Estadual do Maranhão, São Luís, 65055-310, Brazil
Helen Silva Ribeiro
Universidade Estadual do Maranhão, São Luís, 65055-310, Brazil
Aldilene da Silva Lima
Laboratório de Química dos Produtos Naturais, Universidade Federal do Maranhão, 65080-805, São Luís, MA, Brazil
Cláudia Quintino da Rocha
Laboratório de Química dos Produtos Naturais, Universidade Federal do Maranhão, 65080-805, São Luís, MA, Brazil
Kátia da Silva Calabrese
Laboratório de Protozoologia, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, 21041-250, Brazil; Corresponding author.
Ana Lucia Abreu-Silva
Rede Nordeste de Biotecnologia, Universidade Federal do Maranhão, São Luís, 65080-805, Brazil; Universidade Estadual do Maranhão, São Luís, 65055-310, Brazil; Pós-graduação em Ciência Animal, Universidade Estadual do Maranhão, São Luís, 65055-310, Brazil; Corresponding author. Universidade Estadual do Maranhão, São Luís, 65055-310, Brazil
Fernando Almeida-Souza
Universidade Estadual do Maranhão, São Luís, 65055-310, Brazil; Laboratório de Protozoologia, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, 21041-250, Brazil; Pós-graduação em Ciência Animal, Universidade Estadual do Maranhão, São Luís, 65055-310, Brazil
Leishmaniases are infectious-parasitic diseases that impact public health around the world. Antileishmanial drugs presented toxicity and increase in parasitic resistance. Studies with natural products show an alternative to this effect, and several metabolites have demonstrated potential in the treatment of various diseases. Terminalia catappa is a plant species with promising pharmaceutical properties. The objective of this work was to evaluate the therapeutic potential of extracts and fractions of T. catappa on Leishmania amazonensis and investigate the immunomodulatory mechanisms associated with its action. In anti-Leishmania assays, the ethyl acetate fraction exhibited activity against promastigotes (IC50 86.07 ± 1.09 μg/mL) and low cytotoxicity (CC50 517.70 ± 1.68 μg/mL). The ethyl acetate fraction also inhibited the intracellular parasite (IC50 25.74 ± 1.08 μg/mL) with a selectivity index of 20.11. Treatment with T. catappa ethyl acetate fraction did not alter nitrite production by peritoneal macrophages stimulated with L. amazonensis, although there was a decrease in unstimulated macrophages treated at 50 μg/mL (p = 0.0048). The T. catappa ethyl acetate fraction at 100 μg/mL increased TNF-α levels (p = 0.0238) and downregulated HO-1 (p = 0.0030) and ferritin (p = 0.0002) gene expression in L. amazonensis-stimulated macrophages. Additionally, the total flavonoid and ellagic acid content for ethyl acetate fraction was 13.41 ± 1.86 mg QE/g and 79.25 mg/g, respectively. In conclusion, the T. catappa ethyl acetate fraction showed leishmanicidal activity against different forms of L. amazonensis and displayed immunomodulatory mechanisms, including TNF-α production and expression of pro and antioxidant genes.
