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

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.

Keywords: Hyperalgesia; MAPKs quinases; Methyl gallate; NF-κB signaling; Polyphenols; Tlrs.