A Prenylated Xanthone, Cudratricusxanthone A, Isolated from Cudrania tricuspidata Inhibits Lipopolysaccharide-Induced Neuroinflammation through Inhibition of NF-κB and p38 MAPK Pathways in BV2 Microglia

Molecules. 2016 Sep 16;21(9):1240. doi: 10.3390/molecules21091240.

Abstract

Cudrania tricuspidata Bureau (Moraceae) is an important source of traditional Korean and Chinese medicines used to treat neuritis and inflammation. Cudratricusxanthone A (1), a prenylated xanthone, isolated from C. tricuspidata, has a variety of biological and therapeutic activities. The goal of this study was to examine the effects of compound 1 on neuroinflammation and characterize its mechanism of action in lipopolysaccharide (LPS)-stimulated BV2 microglia. Cudratricusxanthone A (1) suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 enzymes and decreased the production of iNOS-derived nitric oxide and COX-2-derived prostaglandin E2 in LPS-stimulated mouse BV2 microglia. The compound also decreased tumor necrosis factor-α, interleukin (IL)-1β, and IL-12 production; inhibited the phosphorylation and degradation of IκB-α; and blocked the nuclear translocation of p50 and p65 in mouse BV2 microglia induced by LPS. Cudratricusxanthone A (1) had inhibitory effects on nuclear factor kappa B DNA-binding activity. Additionally, it inhibited the p38 mitogen-activated protein kinase signaling pathway. Our data suggests that cudratricusxanthone A (1) may be a useful therapeutic agent in the treatment of neurodegenerative diseases caused by neuroinflammation.

Keywords: Cudrania tricuspidata; cudratricusxanthone A; microglia; mitogen-activated protein kinase; neuroinflammation; nuclear factor-kappa B.

MeSH terms

  • Animals
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology
  • Lipopolysaccharides / toxicity*
  • MAP Kinase Signaling System / drug effects*
  • Mice
  • Microglia / metabolism*
  • Microglia / pathology
  • Moraceae / chemistry*
  • NF-kappa B p50 Subunit / metabolism*
  • Transcription Factor RelA / metabolism*
  • Xanthones / chemistry
  • Xanthones / isolation & purification
  • Xanthones / pharmacology*
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Lipopolysaccharides
  • NF-kappa B p50 Subunit
  • Rela protein, mouse
  • Transcription Factor RelA
  • Xanthones
  • cudratricusxanthone A
  • Nfkb1 protein, mouse
  • p38 Mitogen-Activated Protein Kinases