Hostname: page-component-586b7cd67f-t7fkt Total loading time: 0 Render date: 2024-11-25T19:52:20.839Z Has data issue: false hasContentIssue false
  • English
  • Français

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: [email protected]
Get access Rights & Permissions [Opens in a new window]

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 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abath, FG and Werkhauser, RC (1996) The tegument of Schistosoma mansoni: functional and immunological features. Parasite Immunology 18, 15–20.Google Scholar
Abdel-Hafeez, EH, Ahmad, AK, Abdulla, AM, Aabdel-Wahab, S and Mosalem, FA (2012) Therapeutic effect of alpha lipoic acid combined with praziquantel on liver fibrosis induced by Schistosoma mansoni challenged mice. Parasitology Research 111, 577–586.Google Scholar
Alves, TM, Alves, R, Romanha, AJ, Zani, CL, Santos, MH and Nagem, TJ (1999) Biological activities of 7-epiclusianone. Journal of Natural Products 62, 369–371.Google Scholar
Aziz, IA, Yacoub, M, Rashid, L and Solieman, A (2015) Malondialdehyde; lipid peroxidation plasma biomarker correlated with hepatic fibrosis in human Schistosoma mansoni infection. Acta Parasitologica 60, 735–742.Google Scholar
Berman, H, Henrick, K and Nakamura, H (2003) Announcing the worldwide Protein Data Bank. Nature Structural Biology 10, 980.Google Scholar
Bradford, MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry 72, 248–254.Google Scholar
Callahan, HL, Crouch, RK and James, ER (1988) Helminth anti-oxidant enzymes: a protective mechanism against host oxidants? Parasitology Today (Personal Ed.) 4, 218–225.Google Scholar
Cardoso, RMF, Silva, CHTP, De Araújo, APU, Tanaka, T, Tanaka, M and Garratt, RC (2004) Structure of the cytosolic Cu,Zn superoxide dismutase from Schistosoma mansoni. Acta Crystallographica Section D: Biological Crystallography 60, 1569–1578.Google Scholar
Castro, AP, De Mattos, ACA, Pereira, NA, Anchieta, NF, Silva, MS, Dias, DF, Silva, CA, Barros, GV, Souza, RLM, Santos, MH and Marques, MJ (2015) Potent schistosomicidal constituents from Garcinia brasiliensis. Planta Medica 81, 733–741.Google Scholar
Derogis, PBMC, Martins, FT, De Souza, TC, De Moreira, MEC, Souza Filho, JD, Doriguetto, AC, De Souza, KRD, Veloso, MP and Santos, MH (2008) Complete assignment of the 1H and 13C NMR spectra of garciniaphenone and keto-enol equilibrium statements for prenylated benzo-phenones. Magnetic Resonance in Chemistry 46, 278–282.Google Scholar
Draper, HH and Hadley, M (1990) Malondialdehyde determination as index of lipid peroxidation. pp. 421–431 in Wilson, KL and Sonnenberg, A (Eds) Methods in enzymology. Amsterdam, Elsevier.Google Scholar
El-Lakkany, N, El-Din, SS and Ebeid, F (2011) The use of pentoxifylline as adjuvant therapy with praziquantel downregulates profibrogenic cytokines, collagen deposition and oxidative stress in experimental schistosomiasis mansoni. Experimental Parasitology 129, 152–157.Google Scholar
Ferreira, LG, Oliva, G and Andricopulo, AD (2015) Target-based molecular modeling strategies for schistosomiasis drug discovery. Future Medicinal Chemistry 7, 753–764.Google Scholar
Harris, R, Olson, AJ and Goodsell, DS (2007) Automated prediction of ligand-binding sites in proteins. Proteins: structure, function, and bioinformatics 70, 1506–1517.Google Scholar
Hong, Z, Kosman, DJ, Thakur, A, Rekosh, D and LoVerde, PT (1992) Identification and purification of a second form of Cu/Zn superoxide dismutase from Schistosoma mansoni. Infection and Immunity 60, 3641–3651.Google Scholar
Hong, Z, Loverde, PT, Thakur, A, Hammarskjold, ML and Rekosh, D (1993) Schistosoma mansoni: a Cu/Zn superoxide dismutase is glycosylated when expressed in mammalian cells and localizes to a subtegumental region in adult schistosomes. Experimental Parasitology 76, 101–114.Google Scholar
Huang, H (2012) The redox biology of schistosome parasites and applications for drug development. Current Pharmaceutical Design 18, 3595–3611.Google Scholar
Humphrey, W, Dalke, A and Schulten, K (1996) VMD: Visual molecular dynamics. Journal of Molecular Graphics 14, 33–38.Google Scholar
Katz, N, Pellegrino, J and Pereira, JP (1968) Experimental chemotherapy of schistosomiasis III: laboratory and clinical trials with trichlorphone, an organophosphorus compound. Revista Da Sociedade Brasileira de Medicina Tropical 2, 237–245.Google Scholar
Li, G, Chen, J, Wang, C, Xu, Z, Nie, H, Qin, X, Chen, X and Gong, Q (2013) Curcumin protects against acetaminophen-induced apoptosis in hepatic injury. World Journal of Gastroenterology: WJG 19, 7440–7446.Google Scholar
Loria, P, Miller, S, Foley, M and Tilley, L (1999) Inhibition of the peroxidative degradation of haem as the basis of action of chloroquine and other quinoline antimalarials. Biochemical Journal 339, 363–370.Google Scholar
LoVerde, PT, Carvalho-Queiroz, C and Cook, R (2004) Vaccination with antioxidant enzymes confers protective immunity against challenge infection with Schistosoma mansoni. Memórias Do Instituto Oswaldo Cruz 99, 37–43.Google Scholar
Maizels, RM, Bundy, DA, Selkirk, ME, Smith, DF and Anderson, RM (1993) Immunological modulation and evasion by helminth parasites in human populations. Nature 365, 797–805.Google Scholar
Mantawy, MM, Ali, HF and Rizk, MZ (2011) Therapeutic effects of Allium sativum and Allium cepa in Schistosoma mansoni experimental infection. Revista Do Instituto de Medicina Tropical de São Paulo 53, 155–163.Google Scholar
Mclaren, DJU and Hockley, DJ (1977) Blood flukes have a double outer membrane. Nature 269, 147–149.Google Scholar
Mei, H and LoVerde, PT (1997) Schistosoma mansoni: the developmental regulation and immunolocalization of antioxidant enzymes. Experimental Parasitology 86, 69–78.Google Scholar
Morris, GM, Huey, R, Lindstrom, W, Sanner, MF, Belew, RK, Goodsell, DS and Olson, AJ (2009) AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. Journal of Computational Chemistry 30, 2785–2791.Google Scholar
Neves, BJ, Muratov, E, Machado, RB, Andrade, CH and Cravo, PVL (2016) Modern approaches to accelerate discovery of new antischistosomal drugs. Expert Opinion on Drug Discovery 11, 557–567.Google Scholar
Pal, C and Bandyopadhyay, U (2012) Redox-active antiparasitic drugs. Antioxidants & Redox Signaling 17, 555–582.Google Scholar
Pearce, EJ and MacDonald, AS (2002) The immunobiology of schistosomiasis. Nature Reviews. Immunology 2, 499–511.Google Scholar
Peskin, AV and Winterbourn, CC (2000) A microtiter plate assay for superoxide dismutase using a water-soluble tetrazolium salt (WST-1). Clinica Chimica Acta 293, 157–166.Google Scholar
Santa-Cecília, FV, Santos, GB, Fuzissaki, CN, Derogis, PB, Freitas, LA, Gontijo, VS, Stringheta, PC, Nagem, TJ, Brigagão, MR and Santos, MH (2012) 7-Epiclusianone, the natural prenylated benzophenone, inhibits superoxide anions in the neutrophil respiratory burst. Journal of Medicinal Food 15, 200–205.Google Scholar
Santos, MH, Speziali, NL, Nagem, TJ and Oliveira, TT (1998) Epiclusianone: a new natural product derivative of bicyclo[3.3.1]nonane-2,4,9-trione. Acta Crystallographica Section C Crystal Structure Communications 54, 1990–1992.Google Scholar
Santos, MH, Nagem, TJ, Oliveira, TT and Braz-Filho, R (1999) 7-Epiclusianona, a nova benzofenona tetraprenilada e outros constituintes químicos dos frutos de Rheedia gardneriana. Química Nova 22, 654–660.Google Scholar
Sayed, AA, Cook, SK and Williams, DL (2006) Redox balance mechanisms in Schistosoma mansoni rely on peroxiredoxins and albumin and implicate peroxiredoxins as novel drug targets. Journal of Biological Chemistry 281, 17001–17010.Google Scholar
Shalaby, KA, Yin, L, Thakur, A, Christen, L, Niles, EG and LoVerde, PT (2003) Protection against Schistosoma mansoni utilizing DNA vaccination with genes encoding Cu/Zn cytosolic superoxide dismutase, signal peptide-containing superoxide dismutase and glutathione peroxidase enzymes. Vaccine 22, 130–136.Google Scholar
Van Hellemond, JJ, Retra, K, Brouwers, JF, van Balkom, BW, Yazdanbakhsh, M, Shoemaker, CB and Tielens, AG (2006) Functions of the tegument of schistosomes: clues from the proteome and lipidome. International Journal for Parasitology 36, 691–699.Google Scholar
Wallace, AC, Laskowski, RA and Thornton, JM (1995) LIGPLOT: a program to generate schematic diagrams of protein–ligand interactions. Protein Engineering 8, 127–134.Google Scholar
Wang, W, Wang, L and Liang, YS (2012) Susceptibility or resistance of praziquantel in human schistosomiasis: a review. Parasitology Research 111, 1871–1877.Google Scholar
Williams, DL, Bonilla, M, Gladyshev, VN and Salinas, G (2013) Thioredoxin glutathione reductase-dependent redox networks in platyhelminth parasites. Antioxidants & Redox Signaling 19, 735–745.Google Scholar
World Health Organization (2016) Schistosomiasis. Available at www.who.int/mediacentre/factsheets/fs115/en/ (accessed 18 July 2016).Google Scholar
Zor, T and Selinger, Z (1996) Linearization of the Bradford protein assay increases its sensitivity: theoretical and experimental studies. Analytical Biochemistry 236, 302–308.Google Scholar