Anti-inflammatory effects of gallic acid in human gestational tissues in vitro

Reproduction. 2020 Oct;160(4):561-578. doi: 10.1530/REP-20-0249.

Abstract

Spontaneous preterm birth is the leading cause of neonatal mortality and morbidity globally. Activation of the maternal immune system leads to a downstream cascade of proinflammatory events that culminate in the activation of spontaneous uterine contractions and the rupture of the foetal membranes. Anti-inflammatory agents may be a novel therapeutic approach to prevent inflammation-induced myometrial contractions and premature rupture of foetal membranes. The polyphenol gallic acid has been previously shown to exert potent anti-inflammatory effects. Thus, this study aimed to determine the effect of gallic acid on proinflammatory and pro-labour mediators in cytokine-stimulated gestational tissues in vitro. In primary human cells isolated from myometrium and foetal membranes (decidua, and amnion mesenchymal and epithelial cells), gallic acid treatment suppressed inflammation-induced expression of proinflammatory cytokines and chemokines and extracellular matrix-degrading and matrix-remodelling enzymes. Gallic acid also significantly inhibited inflammation-induced myometrial activation as evidenced by decreased expression of contraction-associated proteins, the uterotonic PGF2α and collagen cell contractility. Using a global proteomic approach, gallic acid may differentially regulate proteins associated with collagen synthesis, cell contractility and protein synthesis in primary myometrial and decidual cells. In summary, gallic acid inhibited inflammation-induced mediators involved in active labour in primary cells isolated from myometrium and foetal membranes. These in vitro studies suggest that the polyphenol gallic acid may be able to suppress the production of proinflammatory and pro-labour mediators involved in myometrial contractions and rupture of foetal membranes. Future preclinical studies may elucidate the efficacy of gallic acid in preventing inflammation-driven preterm birth.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Extraembryonic Membranes / metabolism
  • Extraembryonic Membranes / pathology*
  • Female
  • Gallic Acid / pharmacology*
  • Gestational Age
  • Humans
  • In Vitro Techniques
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Myometrium / metabolism
  • Myometrium / pathology*
  • Pregnancy
  • Premature Birth / etiology
  • Premature Birth / metabolism
  • Premature Birth / pathology
  • Premature Birth / prevention & control*
  • Proteome / analysis*
  • Proteome / metabolism

Substances

  • Anti-Inflammatory Agents
  • Proteome
  • Gallic Acid