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The natural compound 7-epiclusianone inhibits superoxide dismutase activity in Schistosoma mansoni

Published online by Cambridge University Press:  04 October 2017

M.S. Silva ,
A.P. Castro ,
A.T. de Castro ,
I.M.M. Souza ,
R.L. Martins-Souza ,
F.A. Colombo ,
T.C. Elias ,
M.H. Santos  and
M.J. Marques
M.S. Silva
Affiliation:
Departamento de Patologia e Parasitologia – Universidade Federal de Alfenas, Minas Gerais, Brazil
A.P. Castro
Affiliation:
Departamento de Patologia e Parasitologia – Universidade Federal de Alfenas, Minas Gerais, Brazil
A.T. de Castro
Affiliation:
Departamento de Patologia e Parasitologia – Universidade Federal de Alfenas, Minas Gerais, Brazil
I.M.M. Souza
Affiliation:
Departamento de Patologia e Parasitologia – Universidade Federal de Alfenas, Minas Gerais, Brazil
R.L. Martins-Souza
Affiliation:
Departamento de Patologia e Parasitologia – Universidade Federal de Alfenas, Minas Gerais, Brazil
F.A. Colombo
Affiliation:
Departamento de Patologia e Parasitologia – Universidade Federal de Alfenas, Minas Gerais, Brazil
T.C. Elias
Affiliation:
Instituto de Ciências Exatas – Universidade Federal de Alfenas, Minas Gerais, Brazil
M.H. Santos
Affiliation:
Departamento de Química – Universidade Federal de Viçosa, Minas Gerais, Brazil
M.J. Marques*
Affiliation:
Departamento de Patologia e Parasitologia – Universidade Federal de Alfenas, Minas Gerais, Brazil
*
Author for correspondence: M.J. Marques, Fax: +55-35-32991472, E-mail: marques@unifal-mg.edu.br
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Abstract

Schistosomiasis – caused by trematodes from the genus Schistosoma – affects more than 200 million people worldwide. Growing resistance to therapy with praziquantel (PZQ) has encouraged the search for novel treatments against this neglected disease. The compound 7-epiclusianone (7-epi) – isolated from ‘bacupari’ (the fruit of the Gracinia brasiliensis tree) – has promising activity against Schistosoma mansoni in vitro, damaging the parasite's tegument. However, the target and mechanism of action of 7-epi have not been identified. Here, we examined the possibility that 7-epi harms the tegument by inhibiting parasite superoxide dismutase (SOD), which protects the tegument from damage by reactive oxygen species produced by host immune cells. Molecular docking analysis in silico suggested strong interactions between 7-epi and S. mansoni cytosolic superoxide dismutase (SmCtSOD) at allosteric cavities. Schistosoma mansoni couples were cultivated ex vivo with 12.44–198.96 μm 7-epi for 24 h, and then parasite extracts were tested for lipid peroxidation (as a surrogate for oxidative stress), and SOD activity and expression. Lipid peroxidation levels increased after incubation with concentrations ≥99.48 μm 7-epi, and this compound reduced SOD activity at concentrations ≥24.87 μm. However, contact with 7-epi did not alter SOD expression, by quantitative real-time polymerase chain reaction (qRT-PCR). Our results show that the inhibition of SmCtSOD is partly responsible for the tegument detachment observed after incubation with 7-epi, but is not the only cause of the antiparasitic action of this compound in vitro.

Type
Research Paper
Information
Journal of Helminthology , Volume 92 , Issue 5 , September 2018 , pp. 535 - 543
Copyright
Copyright © Cambridge University Press 2017 

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