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

被引:79
作者
Chen, Wen-Liang [1 ]
Qian, Yan [1 ]
Meng, Wei-Feng [1 ]
Pang, Ji-Yan [2 ,3 ]
Lin, Yong-Cheng [2 ,3 ]
Guan, Yong-Yuan [1 ]
Chen, Sheng-Pin [3 ]
Liu, Jie [1 ]
Pei, Zhong [4 ]
Wang, Guan-Lei [1 ,3 ]
机构
[1] Sun Yat Sen Univ, Dept Pharmacol, Zhongshan Sch Med, Guangzhou 510080, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Dept Appl Chem, Guangzhou 510080, Guangdong, Peoples R China
[3] Sun Yat Sen Univ, Dept Pharm, Guangzhou 510080, Guangdong, Peoples R China
[4] Sun Yat Sen Univ, Dept Neurol, Affiliated Hosp 1, Guangzhou 510080, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
Xyloktals; Endothelial cells; Oxidized low-density lipoprotein; Reactive oxygen species; Nitric oxide; Nicotinamide adenine dinucleotide phosphate oxidase; LOW-DENSITY-LIPOPROTEIN; HUMAN ENDOTHELIAL-CELLS; NITRIC-OXIDE; NAD(P)H OXIDASE; MAJOR SOURCE; APOPTOSIS; ACTIVATION; ATHEROSCLEROSIS; PHARMACOLOGY; INHIBITION;
D O I
10.1016/j.bcp.2009.05.029
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 mu M) significantly improved oxLDL (150 mu g/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. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:941 / 950
页数:10
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