A novel marine compound xyloketal B protects against oxidized LDL-induced cell injury in vitro.
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.
Chen
Wen-Liang
WL
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, Guangzhou, 510080, PR China.
Qian
Yan
Y
Meng
Wei-Feng
WF
Pang
Ji-Yan
JY
Lin
Yong-Cheng
YC
Guan
Yong-Yuan
YY
Chen
Sheng-Pin
SP
Liu
Jie
J
Pei
Zhong
Z
Wang
Guan-Lei
GL
D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005452:Fluoresceins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D005562:Formazans / Q000032:analysis; D006801:Humans; D007211:Indoles / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D015394:Molecular Structure; D019255:NADPH Oxidases / Q000096:biosynthesis; D009569:Nitric Oxide / Q000096:biosynthesis; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000096:biosynthesis; D011714:Pyrans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D013778:Tetrazolium Salts / Q000032:analysis; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014471:Umbilical Veins / Q000187:drug effects* / Q000378:metabolism; D013098:Xylariales / Q000737:chemistry
C503301:4-amino-5-methylamino-2',7'-difluorofluorescein diacetate; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005562:Formazans; D007211:Indoles; D008077:Lipoproteins, LDL; D011714:Pyrans; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; C099252:oxidized low density lipoprotein; C515343:xyloketal B; D030421:Peroxynitrous Acid; C079782:MTT formazan; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; C007293:DAPI; D019255:NADPH Oxidases