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一种新型海洋化合物木酮糖酮B在体外可保护细胞免受氧化型低密度脂蛋白诱导的损伤。

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

作者信息

Chen Wen-Liang, Qian Yan, Meng Wei-Feng, Pang Ji-Yan, Lin Yong-Cheng, Guan Yong-Yuan, Chen Sheng-Pin, Liu Jie, Pei Zhong, Wang Guan-Lei

机构信息

Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, Guangzhou, 510080, PR China.

出版信息

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.

摘要

木酮糖酮B是一种从红树真菌木霉属(编号2508)中分离出的具有独特化学结构的新型海洋化合物。用木酮糖酮B(0.63 - 40微摩尔)预处理可显著改善氧化型低密度脂蛋白(150微克/毫升)诱导的人脐静脉内皮细胞(HUVECs)损伤,且无毒性或增殖作用。木酮糖酮B浓度依赖性地减弱氧化型低密度脂蛋白诱导的活性氧生成、过氧亚硝酸盐形成以及Bcl - 2表达的降低。此外,木酮糖酮B显著抑制NADPH氧化酶活性以及gp91phox和p47phox的mRNA表达。此外,木酮糖酮B单独使用可增加一氧化氮(NO)的产生。总体而言,这些数据表明木酮糖酮B可能通过抑制NADPH氧化酶衍生的活性氧生成、促进NO产生和恢复Bcl - 2表达来保护内皮细胞免受氧化型低密度脂蛋白诱导的氧化损伤,使其成为一种有前途的化合物,可用于进一步评估其在动脉粥样硬化治疗中的作用。

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