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The Influence of a Xanthine-Catechin Chemical Matrix on in vitro Macrophage-Activation Triggered by Antipsychotic Ziprasidone

  • Thiago Duarte
  • Fernanda BarbisanEmail author
  • Beatriz Sadigurski Nunes da Cunha
  • Verônica Farina Azzolin
  • Bárbara Osmarin Turra
  • Marta Maria Medeiros Frescura Duarte
  • Ivo Emilio da Cruz Jung
  • Euler Esteves Ribeiro
  • Pedro Antônio do Prado-Lima
  • Ivana Beatrice Mânica da Cruz


Ziprasidone (ZIP) is an effective antipsychotic with low side effects than other second-generation antipsychotics. Despite this, there are reports of adverse events and previous studies associating the use of ZIP the inflammatory response. It is possible to infer that bioactive molecules present in some foods could attenuate peripheral inflammatory and oxidative stress potentially triggered ZIP. This is the case of guaraná xanthine-catechin chemical matrix (XC-Mix) that presents caffeine, theobromine, and catechin. The in vitro protocols using murine RAW 264.7 cell macrophages were ZIP-exposure in culture medium supplemented with chemical isolated and admixture of Caf, The, and Cat. Main results showed that supplementation with isolated and XC-mix had a lowering effect on 72 h macrophages proliferation. XC-mix with 1:1:1 proportion at 25 μg/mL of each caffeine, theobromine, and catechin, molecules present lowering effect on nitric oxide levels, oxidative stress markers (DNA oxidation quantified by 8-hydroxy-2′ –deoxyguanosine), lipoperoxidation, and protein carbonylation. XC-mix also decreased protein levels and downregulated genes of proinflammatory cytokines (IL-1β, IL-6, TNF-α). At contrary, XC-Mix increased levels and upregulated gene of anti-inflammatory IL-10 cytokine. The results suggest that XC-matrix could present some beneficial action on peripheral proinflammatory effects ZIP-triggered. Complementary in vivo studies could be useful to confirm these in vitro findings described here.


Caffeine Theobromine Catechin, Paullinia cupana Schizophrenia Cytokine 



PROEX/CAPES number 23038.005848/2018-31 for reading spectrophotometer (SpectraMax® i3x Multi-Mode Microplate Reader).

Availability of Data and Materials

All data generated or analyzed during the current study are included in this article.

Authors’ Contributions

TD and FB designed the research and analyzed and interpreted the data; TD, FB, BSNC, VFA, BOT, and IBMC interpreted the data and wrote the paper; TD, FB, MMMFD, IECJ, and IBM analyzed and interpreted the data; EER and PASPL performed the research and analyzed the data; TD, FB, BSNC, VFA, BOT, and IBMC directed, designed, analyzed, and interpreted the data. All the authors read and approved the final manuscript.


This work was supported by the CNPq [Nos. 402325/2013-3; 490760/2013-9; 311446/2012-4] and CAPES for grants and fellowships. “Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)” and “Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)” for Brazilian financial support.

Compliance with Ethical Standards

Competing Interests

The authors declare that they have no competing interests.

Ethics Approval

It is an in vitro work with the use of cell lines, there is no need for approval by the Ethics Committee.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Thiago Duarte
    • 1
  • Fernanda Barbisan
    • 2
    • 3
    Email author
  • Beatriz Sadigurski Nunes da Cunha
    • 3
  • Verônica Farina Azzolin
    • 2
  • Bárbara Osmarin Turra
    • 3
  • Marta Maria Medeiros Frescura Duarte
    • 4
  • Ivo Emilio da Cruz Jung
    • 1
  • Euler Esteves Ribeiro
    • 5
  • Pedro Antônio do Prado-Lima
    • 6
  • Ivana Beatrice Mânica da Cruz
    • 1
    • 2
  1. 1.Postgraduate Program of PharmacologyFederal University of Santa Maria (UFSM)Santa MariaBrazil
  2. 2.Postgraduate Program of GerontologyFederal University of Santa Maria (UFSM)Santa MariaBrazil
  3. 3.Biogenomic Laboratory, Center of Health SciencesFederal University of Santa Maria (UFSM)Santa MariaBrazil
  4. 4.Center of Health SciencesLutheran University of Brazil (ULBRA)Santa MariaBrazil
  5. 5.Foundation Open University of the Third AgeManausBrazil
  6. 6.Brain InstituteCatholic University of Rio Grande do SulPorto AlegreBrazil

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