| Author | Lima, Gerson S. | |
| Author | Pinto, Denise B. Castro | |
| Author | Machado, Gerzia C. | |
| Author | Maciel, Maria A. M. | |
| Author | Echevarria, Aurea | |
| Access date | 2016-03-01T14:38:52Z | |
| Available date | 2016-03-01T14:38:52Z | |
| Document date | 2015 | |
| Citation | LIMA, Gerson S.; Antileishmanial activity and trypanothione reductase effects of terpenes from the Amazonian species Croton cajucara Benth (Euphorbiaceae). Phytomedicine, v.22, n.12, p.1133-1137, Nov. 2015. | pt_BR |
| ISSN | 0944-7113 | |
| URI | https://www.arca.fiocruz.br/handle/icict/12921 | |
| Language | eng | pt_BR |
| Publisher | Elsevier | pt_BR |
| Rights | restricted access | |
| Title | Antileishmanial activity and trypanothione reductase effects of terpenes from the Amazonian species Croton cajucara Benth (Euphorbiaceae) | pt_BR |
| Type | Article | |
| DOI | 10.1016/j.phymed.2015.08.012 | |
| Abstract | Background: Leishmaniasis comprises several infectious diseases caused by protozoa parasites of Leishmania
genus. In recent years, there has been a growing interest in the therapeutic use of natural products to treat
parasitic diseases. Among them Croton cajucara Benth. (Euphorbiaceae) is a plant found in the Amazonian
region with a history of safe use in folk medicine.
Purpose: The purpose of this study was to investigate the effects of clerodane diterpenes, transdehydrocrotonin
(DCTN), trans-crotonin (CTN) and acetylaleuritolic acid (AAA) obtained from powdered bark
of C. cajucara against promastigotes, axenic and intracellular amastigotes of Leishmania amazonensis. Furthermore,
the effects of DCTN and CTN on the trypanotiona reductase enzyme were also investigated. The
extraction of the terpenes was carried out as previously reported (Maciel et al., 1998; 2003).
Methods: The effect of the isolated compounds (DCTN, CTN and AAA) from the bark of C. cajucara was assessed
in vitro against promastigotes, axenic amastigotes and intracellular amastigotes of L. amazonensis by
counting of remaining parasites in a Neubauer chamber in comparison to pentamidine used as standard drug.
The action of natural products on trypanothione reductase was assessed using soluble protein fraction of promastigotes.
The assays were performed by incubation with HEPES, EDTA, NADPH and trypanothione disulfide
to quantify the NAPH consumption by TryR.
Results: The results showed very high efficacy, especially of the diterpene DCTN, against promastigotes
(IC50 = 6.30 ± 0.06 μg/ml) and axenic amastigotes (IC50 = 19.98 ± 0.05 μg/ml) of L. amazonenesis. The cytotoxic
effect of the best active natural product was evaluated on mouse peritoneal infected macrophages
(IC50 = 0.47 ± 0.03 μg/ml in 24 h of culture), and the treatment revealed that DCTN never reaches toxic
concentrations while reducing the infection and, most importantly, with no toxicity (>100 μg/ml with 0% of
macrophage kill) when compared to pentamidine (37.5 μg/ml with 100% of macrophage kill). Furthermore,
all of the natural products assayed on the trypanothione reductase enzyme inhibited the enzyme activity
compared to the control.
Conclusion: Clerodane diterpenes from C. cajucara showed promising in vitro antileishmanial effects against
L. amazonensis, specially the DCTN with no macrophage toxicity up to the assayed concentration. In addition,
the action on trypanothione reductase enzyme revealed a possible mechanism of action. | pt_BR |
| Affilliation | Universidade Federal Rural do Rio de Janeiro. Instituto de Ciências Exatas. Departamento de Química. Seropédica, RJ, Brasil / Fundação Oswaldo Cruz. Biomanguinhos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanossomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanossomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Potiguar Laureate International Universities. Programa de Pós-graduação em Biotecnologia. Campus Salgado Filho. Natal, RN, Brasil / Universidade Federal do Rio Grande do Norte. Instituto de Química. Campus Lagoa Nova, Natal, RN, Brasil. | pt_BR |
| Affilliation | Universidade Federal Rural do Rio de Janeiro. Instituto de Ciências Exatas. Departamento de Química. Seropédica, RJ, Brasil. | pt_BR |
| Subject | Leishmania amazonensis | pt_BR |
| Subject | Terpenes | pt_BR |
| Subject | trans-Deydrocrotonin | pt_BR |
| Subject | Croton cajucara | pt_BR |
| Subject | Macrophage | pt_BR |
| Subject | Antiprotozoal activity | pt_BR |
| DeCS | Leishmania | pt_BR |
| DeCS | Terpenos | pt_BR |
| DeCS | Macrófagos | pt_BR |
| DeCS | Antiprotozoários | pt_BR |
| DeCS | Euphorbiaceae | pt_BR |
