Phytomedicine, volume 46, pages 11-20
Grandiflorenic acid promotes death of promastigotes via apoptosis-like mechanism and affects amastigotes by increasing total iron bound capacity
Bruna Bortoleti
1
,
Manoela Daiele Gonçalves
2
,
Fernanda Tomiotto-Pellissier
1
,
Milena Menegazzo Miranda Sapla
1
,
João Paulo Assolini
1
,
Amanda Carloto
1
,
Priscila Do Carmo Freitas De Carvalho
3
,
Ian Lucas Alves Cardoso
2
,
ANDRÉA NAME COLADO SIMÃO
4
,
Nilton S Arakawa
2
,
Idessania Nazareth Costa
1
,
Ivete Conchon-Costa
1
,
Wander Rogério Pavanelli
1
1
Laboratory of Experimental Protozoology, Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, PR, Brazil
|
2
Laboratory of Biotransformation and Phytochemistry, Department of Chemistry, Center of Exact Sciences, State University of Londrina, PR, Brazil
|
3
Laboratory of Research on Bioactive Molecules, Department of Chemistry, Center of Exact Sciences, State University of Londrina, PR, Brazil
|
4
Laboratory of Applied Immunology Research, Department of Pathology Science, Clinical Analysis and Toxicology, Health Sciences Center, State University of Londrina, Londrina, PR, Brazil
|
Publication type: Journal Article
Publication date: 2018-07-01
Journal:
Phytomedicine
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 7.9
ISSN: 09447113, 1618095X
Drug Discovery
Pharmacology
Pharmaceutical Science
Molecular Medicine
Complementary and alternative medicine
Abstract
American tegumentary leishmaniasis (ATL) is a zoonotic disease caused by protozoa of the genus Leishmania. The high toxicity, high costs and resistance of some strains to current drugs has prompted the search for therapeutic alternatives for the management of this disease. Sphagneticola trilobata is a plant that has diterpenes as main constituents, including grandiflorenic acid (GFA) that has antiinflammatory, antiprotozoal, antibacterial and antinociceptive activity.The aim of our study was to determine the effect of GFA on both the promastigotes and the amastigotes of Leishmania amazonensis.Isolation by chromatographic methods and chemical identification of GFA, then evaluation of the in vitro leishmanicidal activity of this compound against Leishmania amazonensis promastigotes and L. amazonensis infected peritoneal Balb/c macrophages, as well its action and microbicide mechanisms.GFA treatment significantly inhibited the proliferation of promastigotes. This antiproliferative effect was accompanied by morphological changes in the parasite with 25 nM GFA. Afterwards, we investigated the mechanisms involved in the death of the protozoan; there was an increase in the production of reactive oxygen species (ROS), phosphatidylserine exposure, permeabilization of the plasma membrane and decreased mitochondrial depolarization. In addition, we observed that the treatment caused a reduction in the percentage of infected cells and the number of amastigotes per macrophage, without showing cytotoxicity in low doses to peritoneal macrophages and sheep erythrocytes. GFA increased IL-10 and total iron bound to transferrin in infected macrophages. Our results showed that GFA treatment acts on promastigote forms through an apoptosis-like mechanism and on intracellular amastigote forms, dependent of regulatory cytokine IL-10 modulation with increase in total iron bound to transferrin.GFA showed in vitro antileishmanial activity on L. amazonensis promastigotes forms and on L. amazonensis-infected macrophages.
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- We do not take into account publications without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Bortoleti B. et al. Grandiflorenic acid promotes death of promastigotes via apoptosis-like mechanism and affects amastigotes by increasing total iron bound capacity // Phytomedicine. 2018. Vol. 46. pp. 11-20.
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Bortoleti B., Gonçalves M. D., Tomiotto-Pellissier F., Miranda Sapla M. M., Assolini J. P., Carloto A., De Carvalho P. D. C. F., Cardoso I. L. A., SIMÃO A. N. C., Arakawa N. S., Costa I. N., Conchon-Costa I., Pavanelli W. R. Grandiflorenic acid promotes death of promastigotes via apoptosis-like mechanism and affects amastigotes by increasing total iron bound capacity // Phytomedicine. 2018. Vol. 46. pp. 11-20.
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TY - JOUR
DO - 10.1016/j.phymed.2018.06.010
UR - https://doi.org/10.1016/j.phymed.2018.06.010
TI - Grandiflorenic acid promotes death of promastigotes via apoptosis-like mechanism and affects amastigotes by increasing total iron bound capacity
T2 - Phytomedicine
AU - Bortoleti, Bruna
AU - Gonçalves, Manoela Daiele
AU - Tomiotto-Pellissier, Fernanda
AU - Miranda Sapla, Milena Menegazzo
AU - Assolini, João Paulo
AU - Carloto, Amanda
AU - De Carvalho, Priscila Do Carmo Freitas
AU - Cardoso, Ian Lucas Alves
AU - SIMÃO, ANDRÉA NAME COLADO
AU - Arakawa, Nilton S
AU - Costa, Idessania Nazareth
AU - Conchon-Costa, Ivete
AU - Pavanelli, Wander Rogério
PY - 2018
DA - 2018/07/01
PB - Elsevier
SP - 11-20
VL - 46
SN - 0944-7113
SN - 1618-095X
ER -
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@article{2018_Bortoleti,
author = {Bruna Bortoleti and Manoela Daiele Gonçalves and Fernanda Tomiotto-Pellissier and Milena Menegazzo Miranda Sapla and João Paulo Assolini and Amanda Carloto and Priscila Do Carmo Freitas De Carvalho and Ian Lucas Alves Cardoso and ANDRÉA NAME COLADO SIMÃO and Nilton S Arakawa and Idessania Nazareth Costa and Ivete Conchon-Costa and Wander Rogério Pavanelli},
title = {Grandiflorenic acid promotes death of promastigotes via apoptosis-like mechanism and affects amastigotes by increasing total iron bound capacity},
journal = {Phytomedicine},
year = {2018},
volume = {46},
publisher = {Elsevier},
month = {jul},
url = {https://doi.org/10.1016/j.phymed.2018.06.010},
pages = {11--20},
doi = {10.1016/j.phymed.2018.06.010}
}