Suppression of lipopolysaccharide-induced COX-2 expression via p38MAPK, JNK, and C/EBPβ phosphorylation inhibition by furomagydarin A, a benzofuran glycoside from Magydaris pastinacea

J Enzyme Inhib Med Chem. 2024 Dec;39(1):2287420. doi: 10.1080/14756366.2023.2287420. Epub 2023 Dec 7.

Abstract

The phytochemical investigation of the methanol extract of the seeds of Magydaris pastinacea afforded two undescribed benzofuran glycosides, furomagydarins A-B (1, 2), together with three known coumarins. The structures of the new isolates were elucidated after extensive 1D and 2D NMR experiments as well as HR MS. Compound 1 was able to inhibit the COX-2 expression in RAW264.7 macrophages exposed to lipopolysaccharide, a pro-inflammatory stimulus. RT-qPCR and luciferase reporter assays suggested that compound 1 reduces COX-2 expression at the transcriptional level. Further studies highlighted the capability of compound 1 to suppress the LPS-induced p38MAPK, JNK, and C/EBPβ phosphorylation, leading to COX-2 down-regulation in RAW264.7 macrophages.

Keywords: C/EBPβ; COX-2; JNK; Magydaris pastinacea; benzofurans; p38MAPK.

MeSH terms

  • Benzofurans* / pharmacology
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Cyclooxygenase 2 / metabolism
  • Glycosides* / pharmacology
  • Lipopolysaccharides / pharmacology
  • MAP Kinase Kinase 4 / metabolism
  • Magnoliopsida / chemistry
  • NF-kappa B / metabolism
  • Phosphorylation
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Benzofurans
  • CCAAT-Enhancer-Binding Protein-beta
  • Cyclooxygenase 2
  • Glycosides
  • Lipopolysaccharides
  • NF-kappa B
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4