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, Claúdia Quintino da Rocha, Kátia da Silva Calabrese, Ana Lúcia Abreu Silva, Fernando Almeida-Souza
Abstract
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 (IC 50 86.07 ± 1.09 μg/mL) and low cytotoxicity (CC 50 517.70 ± 1.68 μg/mL). The ethyl acetate fraction also inhibited the intracellular parasite (IC 50 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.