Abstract
Schistosomiasis, a chronic disease that affects million people worldwide, is caused by trematode flukes of the genus Schistosoma. The lack of an anti-schistosomiasis vaccine and massive monotherapy with praziquantel reinforces the need for search and development of new therapeutic drugs. Recently, we demonstrated that the essential oil of Piper cubeba L., Piperaceae, and their derivative diben-zylbutyrolactolic (−)-6,6′-dinitrohinokinin, presents in vitro and in vivo activities against Schistosoma mansoni. Here, we identified changes in the protein expression after exposure to dibenzylbutyrolac-tolic (−)-6,6′-dinitrohinokinin. We applied two-dimensional gel electrophoresis (2-DE) to S. mansoni soluble protein extracts and observed at least 38 spots to be affected by dibenzylbutyrolactolic (−)-6,6′-dinitrohinokinin. We further identified 25 differentially expressed proteins by mass spectrometry. Enrichment for biological processes and predictive analyses of protein-protein interactions suggest that dibenzylbutyrolactolic (−)-6,6′-dinitrohinokinin targets proteins involved mainly in metabolic processes, especially carbohydrate metabolism. In summary, this study provides an interesting approach to understand the anti-parasitic activity of semi-synthetic (−)-6,6′-dinitrohinokinin a derivative compound from lignan and for the development of new therapy strategies.
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Acknowledgments
The authors thank the Laboratório Nacional de Biociências, Brasil, CNPEM-ABTLUS, Campinas, Brazil, for support with the mass spectrometric analysis. This project was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo, Brasil (grant numbers 1998/14956-7 and 2010/17378-8 and scholarships 2009/15207-4, 2013/00382-0 and 2011/23819).
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TCL, MLAS, RSL and JKB contributed by synthesis of DNH and drafting the paper. LGM, RGP, DPG and ERM contributed by proteome analysis and drafting the paper. LGM, LGG and GRG contributed by analyzing the data. APY, VR, AASF and WRC supervised the proteome analysis and critically read the manuscript.
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Magalhàes, L.G., Lima, T.C., de Paula, R.G. et al. Effects of (−)-6,6′-dinitrohinokinin on adult worms of Schistosoma mansoni: a proteomic analyses. Rev. Bras. Farmacogn. 26, 334–341 (2016). https://doi.org/10.1016/j.bjp.2016.02.001
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DOI: https://doi.org/10.1016/j.bjp.2016.02.001