A novel marine compound xyloketal B protects against oxidized LDL-induced cell injury in vitro

Biochem Pharmacol. 2009 Oct 15;78(8):941-50. doi: 10.1016/j.bcp.2009.05.029. Epub 2009 May 27.

Abstract

Xyloketal B is a novel marine compound with unique chemical structure isolated from mangrove fungus Xylaria sp. (no. 2508). Pretreatment with xyloketal B (0.63-40 microM) significantly improved oxLDL (150 microg/ml)-induced injury in human umbilical vein endothelial cells (HUVECs) without either toxic or proliferative effects. Xyloketal B concentration-dependently attenuated oxLDL-induced ROS generation, peroxynitrite formation and decrease of Bcl-2 expression. In addition, xyloketal B significantly inhibited NADPH oxidase activity, as well as mRNA expression of gp91phox and p47phox. Furthermore, xyloketal B alone augmented the production of nitric oxide (NO). Collectively, these data indicate that xyloketal B protects against oxLDL-induced endothelial oxidative injury probably through inhibiting NADPH oxidase-derived ROS generation, promoting NO production and restoring Bcl-2 expression, making it a promising compound for further evaluation in the treatment of atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Fluoresceins / metabolism
  • Fluorescent Dyes / metabolism
  • Formazans / analysis
  • Humans
  • Indoles / metabolism
  • Lipoproteins, LDL / pharmacology*
  • Molecular Structure
  • NADPH Oxidases / biosynthesis
  • Nitric Oxide / biosynthesis
  • Oxidation-Reduction
  • Peroxynitrous Acid / biosynthesis
  • Pyrans / chemistry
  • Pyrans / isolation & purification
  • Pyrans / pharmacology*
  • Reactive Oxygen Species / analysis
  • Reactive Oxygen Species / metabolism
  • Tetrazolium Salts / analysis
  • Time Factors
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism
  • Umbilical Veins / drug effects*
  • Umbilical Veins / metabolism
  • Xylariales / chemistry

Substances

  • 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate
  • Fluoresceins
  • Fluorescent Dyes
  • Formazans
  • Indoles
  • Lipoproteins, LDL
  • Pyrans
  • Reactive Oxygen Species
  • Tetrazolium Salts
  • oxidized low density lipoprotein
  • xyloketal B
  • Peroxynitrous Acid
  • MTT formazan
  • Nitric Oxide
  • 3-nitrotyrosine
  • Tyrosine
  • DAPI
  • NADPH Oxidases