Prenylated Polyphenols from Broussonetia kazinoki as Inhibitors of Nitric Oxide Production

Molecules. 2018 Mar 12;23(3):639. doi: 10.3390/molecules23030639.

Abstract

Excessive nitric oxide (NO) production by macrophages has been involved in inflammatory diseases. Seven polyphenols (1-7) were isolated from Broussonetia kazinoki (B. kazinoki) and investigated as potential inhibitors of NO overproduction in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Among them, four prenylated polyphenols (2-4 and 6) with a catechol moiety efficiently suppressed the LPS-induced high level of NO with IC50 values of less than 6 µM. The compounds 2-4 and 6 also attenuated protein and mRNA levels of inducible nitric oxide synthase (iNOS). Moreover, they suppressed the nuclear factor κB (NF-κB) activity by inhibiting the degradation of inhibitory-κB-α (I-κB-α) and the translocation of NF-κB into the nucleus in LPS-activated macrophages. Taken together, these findings suggest that polyphenols from B. kazinoki might be beneficial for treatment of inflammatory diseases.

Keywords: Broussonetia kazinoki; inducible nitric oxide synthase; nitric oxide; nuclear factor κB; prenylated polyphenols.

MeSH terms

  • Animals
  • Antioxidants / chemistry
  • Antioxidants / isolation & purification*
  • Antioxidants / pharmacology*
  • Broussonetia / chemistry*
  • Down-Regulation
  • Lipopolysaccharides / adverse effects
  • Mice
  • Molecular Structure
  • NF-KappaB Inhibitor alpha / metabolism
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Polyphenols / chemistry
  • Polyphenols / isolation & purification*
  • Polyphenols / pharmacology*
  • Prenylation
  • Protein Transport / drug effects
  • RAW 264.7 Cells

Substances

  • Antioxidants
  • Lipopolysaccharides
  • NF-kappa B
  • Plant Extracts
  • Polyphenols
  • NF-KappaB Inhibitor alpha
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse