Oral administration of the flavonoid myricitrin prevents dextran sulfate sodium-induced experimental colitis in mice through modulation of PI3K/Akt signaling pathway

Authors

  • Raquel Cristina Schwanke,

    1. Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil
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  • Rodrigo Marcon,

    1. Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil
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  • Flavia Carla Meotti,

    1. Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil
    2. Department of Biochemistry, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil
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  • Allisson Freire Bento,

    1. Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil
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  • Rafael Cypriano Dutra,

    1. Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil
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  • Moacir Geraldo Pizzollatti,

    1. Department of Chemistry, Center of Physical and Mathematical Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil
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  • João B. Calixto

    Corresponding author
    1. Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil
    • Correspondence: Dr. João B. Calixto, Departamento de Farmacologia, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Bloco D, CCB, Caixa Postal 476, CEP 88049–900, Florianópolis, SC, Brazil

      E-mail: calixto@farmaco.ufsc.br or calixto3@terra.com.br

      Fax: +55-48-3337-5479

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Abstract

Scope

We investigated the protective effect of the flavonoid myricitrin in dextran sulfate sodium (DSS) induced colitis as promising candidate for the treatment of ulcerative colitis which is considered an important worldwide public health problem.

Methods and results

Male CD1 mice were provided with a solution of filtered water containing 3% w/v DSS ad libitum over a 5-day period followed by 2 days with normal drinking water. Myricitrin was administered orally, once a day, at the doses 1, 3, and 10 mg/kg of body weight. At the end of day 7th, the animals were euthanized and the colonic tissue was collected to be analyzed by RT-PCR, immunohistochemistry and Western blot. Our results showed that oral treatment with myricitrin exerts consistent anti-inflammatory action in DSS-induced acute colitis in mice by the inhibition of the Akt/phosphatidylinositol-3 kinase-dependent phosphorylation. Consequently, the phosphorylation of mitogen-activated protein kinases (MAPK) p38, extracellular signal-regulated protein kinase (ERK1/2), and c-Jun N-terminal kinase and of the nuclear factor B (NF-κB) was reduced and prevented an increase in the cytokines/chemokines levels.

Conclusion

Together, these data reveal that the anti-inflammatory effect of myricitrin in DSS-induced colitis in mice is likely associated with its ability to prevent the activation of upstream kinases, such as phosphatidylinositol-3 kinase-dependent Akt, NF-κB, and mitogen-activated protein kinase.

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