Laboratory of Applied Pharmacology, Farmanguinhos, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil.
National Institute for Science and Technology on Innovation on Diseases of Neglected Populations (INCT/IDPN), Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Inflamm Res. 2020 Dec;69(12):1257-1270. doi: 10.1007/s00011-020-01407-0. Epub 2020 Oct 9.
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.
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 Pam3CSK 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, Pam3CSK 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.
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.
没食子酸甲酯（MG）是植物界中常见的多酚类化合物，可能与几种药用植物的功效有关。尽管多酚具有治疗作用已被广泛报道，但很少有研究表明 MG 具有抗炎作用。本研究旨在探讨 MG 抗炎活性的分子机制及其对痛觉过敏的影响。
用不同剂量的 MG 预处理瑞士小鼠，然后用酵母聚糖进行 i.pl. 注射以诱导爪肿胀。使用 RAW264.7 巨噬细胞和用不同 TLR 激动剂（如酵母聚糖、LPS 或 Pam3CSK）刺激的 BMDMs 来研究 MG 的分子机制。
MG 抑制酵母聚糖诱导的爪肿胀和痛觉过敏，并调节炎症发展至关重要的分子途径。用 MG 预处理可抑制由酵母聚糖、Pam3CSK 或 LPS 刺激的 RAW 264.7 细胞产生细胞因子和 NF-κB 活性，但对 PMA 无作用。此外，MG 预处理可减少 IκB 降解、NF-κBp65、c-jun 和 c-fos 的核易位以及 ERK1/2、p38 和 JNK 磷酸化。
因此，本研究的结果表明 MG 具有有希望的抗炎作用，并通过抑制 NF-κB 信号通路和 MAPK 通路来解释其作用机制。
