Flavonoid diversity and roles in the lipopolysaccharide-mediated inflammatory response of monocytes and macrophages

Future Med Chem. 2024 Jan;16(1):75-99. doi: 10.4155/fmc-2023-0174. Epub 2024 Jan 11.

Abstract

Targeting lipopolysaccharide (LPS)/toll-like receptor 4 signaling in mononuclear phagocytes has been explored for the treatment of inflammation and inflammation-related disorders. However, only a few key targets have been translated into clinical applications. Flavonoids, a class of ubiquitous plant secondary metabolites, possess a privileged scaffold which serves as a valuable template for designing pharmacologically active compounds directed against diseases with inflammatory components. This perspective provides a general overview of the diversity of flavonoids and their multifaceted mechanisms that interfere with LPS-induced signaling in monocytes and macrophages. Focus is placed on flavonoids targeting MD-2, IκB kinases, c-Jun N-terminal kinases, extracellular signal-regulated kinase, p38 MAPK and PI3K/Akt or modulating LPS-related gene expression.

Keywords: flavonoids; inflammatory responses; lipopolysaccharides; macrophages; monocytes.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Flavonoids / pharmacology
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Lipopolysaccharides* / pharmacology
  • Macrophages / metabolism
  • Monocytes* / metabolism
  • NF-kappa B / metabolism
  • Phosphatidylinositol 3-Kinases
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Lipopolysaccharides
  • Phosphatidylinositol 3-Kinases
  • Flavonoids
  • p38 Mitogen-Activated Protein Kinases
  • NF-kappa B