Caryocar coriaceum extracts exert leishmanicidal effect acting in promastigote forms by apoptosis-like mechanism and intracellular amastigotes by Nrf2/HO-1/ferritin dependent response and iron depletion

• Published in: Biomedicine & pharmacotherapy 2018-02, Vol.98, p.662-672
• Main Authors: Tomiotto-Pellissier, Fernanda, Alves, Daniela Ribeiro, Miranda-Sapla, Milena Menegazzo, de Morais, Selene Maia, Assolini, João Paulo, da Silva Bortoleti, Bruna Taciane, Gonçalves, Manoela Daiele, Cataneo, Allan Henrique Depieri, Kian, Danielle, Madeira, Tiago Bervelieri, Yamauchi, Lucy Megumi, Nixdorf, Suzana Lucy, Costa, Idessania Nazareth, Conchon-Costa, Ivete, Pavanelli, Wander Rogério
• Format: Article
• Language: English
• Subjects: Ferritin; Heme oxygenase-1; Leishmania amazonensis; Nrf2; Oxydative stress
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2017.12.083

[Display omitted] •C. coriaceum induced L. amazonensis promastigote death by apoptosis-like process.•C. coriaceum reduced the L. amazonensis-infection on macrophages.•C. coriaceum reduced the levels of MDA and ROS on infected macrophages.•C. coriaceum up-regulated Nrf2/HO-1/Ferritin expression.•C. coriaceum caused depletion of iron for L. amazonensis amastigotes replication. Leishmania (L.) amazonensis is the American Cutaneous Leishmaniasis-causing agents, and the available drugs for this disease present toxicity, low efficiency and difficulty of administration. Plants belong23ing to the Caryocar genus are found in Brazilian Cerrado, where fruits are used as food and in folk medicine, and previous studies showed several biological effects of extracts of this plant. The present work evaluated the leishmanicidal and immunomodulatory activity of ethyl acetate (EAC) and methanol (MET) C. coriaceum leaf extracts EAC and MET showed an antipromastigote effect after 24, 48 and 72 h. The extracts also induced loss of mitochondrial membrane potential, reactive oxygen species (ROS) production, damage to the plasma membrane, and phosphatidylserine exposure on promastigote forms, and most parasites were going through a late apoptosis-like process. The range of concentrations used did not alter the viability of peritoneal macrophages of BALB/c mice; therefore, we observed that the treatment with extracts was able to reduce the infection of this cells. Thereafter, the extracts were able to significantly improve the levels of TNFα, IL-6, MCP-1, and IL-10, and reduced the levels of MDA and ROS without interfering on NO levels released by infected macrophages. In addition, both EAC and MET up-regulated Nrf2/HO-1/Ferritin expression and reduced the labile iron pool in infected macrophages. Based on the data obtained, it is possible to infer that different solvent extracts of the C. coriaceum leaves exert leishmanicidal effect, acting on promastigote forms through apoptosis-like mechanisms and intracellular amastigote forms involving a Nrf2/HO-1 dependent antioxidant response, which culminates in a depletion of available iron for L. amazonensis replication.