Leishmanicidal and immunomodulatory activity of Terminalia catappa in Leishmania amazonensis in vitro infection

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 trea...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2024-01-01
Series:Heliyon
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405844024006534
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author 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
author_facet 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
author_sort Sandra Alves de Araújo
collection DOAJ
description 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.
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spelling doaj.art-6489806f14b444a0aa08f2b69e637bab2024-02-03T06:38:03ZengElsevierHeliyon2405-84402024-01-01102e24622Leishmanicidal and immunomodulatory activity of Terminalia catappa in Leishmania amazonensis in vitro infectionSandra Alves de Araújo0Carla Maria Pereira Silva1Carolina Silva Costa2Clarissa Sousa Costa Ferreira3Helen Silva Ribeiro4Aldilene da Silva Lima5Cláudia Quintino da Rocha6Kátia da Silva Calabrese7Ana Lucia Abreu-Silva8Fernando Almeida-Souza9Rede Nordeste de Biotecnologia, Universidade Federal do Maranhão, São Luís, 65080-805, BrazilUniversidade Estadual do Maranhão, São Luís, 65055-310, BrazilUniversidade Estadual do Maranhão, São Luís, 65055-310, BrazilUniversidade Estadual do Maranhão, São Luís, 65055-310, BrazilUniversidade Estadual do Maranhão, São Luís, 65055-310, BrazilLaboratório de Química dos Produtos Naturais, Universidade Federal do Maranhão, 65080-805, São Luís, MA, BrazilLaboratório de Química dos Produtos Naturais, Universidade Federal do Maranhão, 65080-805, São Luís, MA, BrazilLaboratório de Protozoologia, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, 21041-250, Brazil; Corresponding author.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, BrazilUniversidade 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, BrazilLeishmaniases 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.http://www.sciencedirect.com/science/article/pii/S2405844024006534Leishmania amazonensisNatural productsFlavonoidEllagic acidImmunomodulationTreatment
spellingShingle 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
Leishmanicidal and immunomodulatory activity of Terminalia catappa in Leishmania amazonensis in vitro infection
Heliyon
Leishmania amazonensis
Natural products
Flavonoid
Ellagic acid
Immunomodulation
Treatment
title Leishmanicidal and immunomodulatory activity of Terminalia catappa in Leishmania amazonensis in vitro infection
title_full Leishmanicidal and immunomodulatory activity of Terminalia catappa in Leishmania amazonensis in vitro infection
title_fullStr Leishmanicidal and immunomodulatory activity of Terminalia catappa in Leishmania amazonensis in vitro infection
title_full_unstemmed Leishmanicidal and immunomodulatory activity of Terminalia catappa in Leishmania amazonensis in vitro infection
title_short Leishmanicidal and immunomodulatory activity of Terminalia catappa in Leishmania amazonensis in vitro infection
title_sort leishmanicidal and immunomodulatory activity of terminalia catappa in leishmania amazonensis in vitro infection
topic Leishmania amazonensis
Natural products
Flavonoid
Ellagic acid
Immunomodulation
Treatment
url http://www.sciencedirect.com/science/article/pii/S2405844024006534
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