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
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Survival / drug effects
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Cells, Cultured
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Dose-Response Relationship, Drug
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Endothelial Cells / drug effects*
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Endothelial Cells / metabolism
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Endothelium, Vascular / drug effects*
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Endothelium, Vascular / metabolism
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Endothelium, Vascular / pathology
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Fluoresceins / metabolism
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Fluorescent Dyes / metabolism
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Formazans / analysis
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Humans
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Indoles / metabolism
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Lipoproteins, LDL / pharmacology*
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Molecular Structure
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NADPH Oxidases / biosynthesis
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Nitric Oxide / biosynthesis
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Oxidation-Reduction
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Peroxynitrous Acid / biosynthesis
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Pyrans / chemistry
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Pyrans / isolation & purification
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Pyrans / pharmacology*
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Reactive Oxygen Species / analysis
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Reactive Oxygen Species / metabolism
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Tetrazolium Salts / analysis
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Time Factors
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Tyrosine / analogs & derivatives
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Tyrosine / metabolism
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Umbilical Veins / drug effects*
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Umbilical Veins / metabolism
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Xylariales / chemistry
Substances
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4-amino-5-methylamino-2',7'-difluorofluorescein diacetate
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Fluoresceins
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Fluorescent Dyes
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Formazans
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Indoles
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Lipoproteins, LDL
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Pyrans
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Reactive Oxygen Species
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Tetrazolium Salts
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oxidized low density lipoprotein
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xyloketal B
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Peroxynitrous Acid
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MTT formazan
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Nitric Oxide
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3-nitrotyrosine
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Tyrosine
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DAPI
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NADPH Oxidases