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Methyl gallate attenuates inflammation induced by Toll-like receptor ligands by inhibiting MAPK and NF-Κb signaling pathways

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Abstract

Objective and design

Methyl gallate (MG) is a prevalent polyphenol in the plant kingdom, which may be related to the effects of several medicinal plants. Although it is widely reported that polyphenols have therapeutic effects, there are few studies demonstrating that MG has anti-inflammatory action. This study aimed to investigate the molecular mechanism behind the anti-inflammatory activity of MG and its effect on hyperalgesia.

Methods

Swiss mice were pretreated orally with different doses of MG and subjected to i.pl. injection of zymosan to induce paw edema. RAW264.7 macrophages and BMDMs stimulated with different TLR agonists such as zymosan, LPS, or Pam3CSK4 were used to investigate the molecular mechanisms of MG

Results

MG inhibits zymosan-induced paw edema and hyperalgesia and modulates molecular pathways crucial for inflammation development. Pretreatment with MG inhibited cytokines production and NF-κB activity by RAW 264.7 cells stimulated with zymosan, Pam3CSK4 or LPS, but not with PMA. Moreover, pretreatment with MG decreased IκB degradation, nuclear translocation of NF-κBp65, c-jun and c-fos and ERK1/2, p38 and JNK phosphorylation.

Conclusion

Thus, the results of this study demonstrate that MG has a promising anti-inflammatory effect and suggests an explanation of its mechanism of action through the inhibition of NF-κB signaling and the MAPK pathway.

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Acknowledgments

This work was supported by grants from the Carlos Chagas Filho, the Rio de Janeiro State Research Supporting Foundation (FAPERJ) – Cientistas de Nosso Estado Nº E-26/202.887/2018; Brazilian Council for Scientific and Technological Development (CNPq)–313443/2018-1; Oswaldo Cruz Foundation (FIOCRUZ) Projeto INOVA Geração do Conhecimento Nº 1531. L. B. Correa was supported by a fellowship from the Coordination for the Improvement of Higher Education Personnel (CAPES), as student of the Post-graduation Program in Cellular and Molecular Biology from Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil. The authors are grateful to Tatiana Almeida Pádua for providing help on graphical preparation.

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Authors and Affiliations

  1. Laboratory of Applied Pharmacology, Farmanguinhos, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil

    Luana Barbosa Correa, Leonardo Noboru Seito, Maria G. Henriques & Elaine Cruz Rosas

  2. National Institute for Science and Technology on Innovation on Diseases of Neglected Populations (INCT/IDPN), Oswaldo Cruz Foundation, Rio de Janeiro, Brazil

    Luana Barbosa Correa, Leonardo Noboru Seito, Maria G. Henriques & Elaine Cruz Rosas

  3. Department of Pathology, Center for Biological Sciences, State University of Londrina, Paraná, Brazil

    Marília F. Manchope & Waldiceu A. Verri Jr

  4. Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil

    Thiago Mattar Cunha

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  1. Luana Barbosa Correa
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  2. Leonardo Noboru Seito
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  3. Marília F. Manchope
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  4. Waldiceu A. Verri Jr
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  7. Elaine Cruz Rosas
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Contributions

CLB; SLN, and REC designed and performed experiments; analyzed data and wrote the paper. MMF performed experiments and analyzed data. CTM and VWA designed, supervised experiments and assisted in drafting this manuscript. REC and HMG conceived the study, designed and supervised experiments and assisted in drafting this manuscript.

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Correspondence to Maria G. Henriques or Elaine Cruz Rosas.

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Correa, L.B., Seito, L.N., Manchope, M.F. et al. Methyl gallate attenuates inflammation induced by Toll-like receptor ligands by inhibiting MAPK and NF-Κb signaling pathways. Inflamm. Res. 69, 1257–1270 (2020). https://doi.org/10.1007/s00011-020-01407-0

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