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海洋褐藻岩藻依聚糖对小胶质细胞中环氧化酶-2 和诱导型一氧化氮合酶的抑制作用及分子机制。

Inhibitory effects and molecular mechanism of dieckol isolated from marine brown alga on COX-2 and iNOS in microglial cells.

机构信息

Department of Marine Life Science and Marine Life Research Center, Chosun University, Gwangju 501-759, Republic of Korea.

出版信息

J Agric Food Chem. 2009 May 27;57(10):4439-46. doi: 10.1021/jf9003913. Epub 2009 May 1.

DOI:10.1021/jf9003913
PMID:19408937
Abstract

To identify the neuroprotective effect of dieckol, a hexameric compound of phloroglucinol isolated from marine brown alga, Ecklonia cava , this study investigated the anti-inflammatory effect of dieckol on lipopolysaccharide (LPS)-stimulated murine BV2 microglia and elucidated the molecular mechanism. The results showed that dieckol suppresses LPS-induced production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner, without causing cytotoxicity. It also significantly reduced the generation of proinflammatory cytokines, such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Moreover, dieckol significantly reduced LPS-induced nuclear factor κB (NF-κB) and p38 mitogen-activated protein kinases (MAPKs) activation, as well as reactive oxygen species (ROS) production. Taken together, the inhibition of LPS-induced NO and PGE(2) production might be due to the suppression of NF-κB and p38 MAPK signal pathway and, at least in part, by inhibiting the generation of ROS. Hence, these effects of dieckol might assist therapeutic treatment for neurodegenerative diseases that are accompanied by microglial activation.

摘要

为了确定从海洋褐藻裙带菜中分离得到的六聚体化合物二苯并庚烷的神经保护作用,本研究探讨了二苯并庚烷对脂多糖(LPS)刺激的小鼠 BV2 小胶质细胞的抗炎作用,并阐明了其分子机制。结果表明,二苯并庚烷呈剂量依赖性抑制 LPS 诱导的一氧化氮(NO)和前列腺素 E2(PGE2)的产生以及诱导型一氧化氮合酶(iNOS)和环氧化酶-2(COX-2)的表达,同时没有细胞毒性。它还显著降低了促炎细胞因子白细胞介素(IL)-1β和肿瘤坏死因子(TNF)-α的产生。此外,二苯并庚烷显著降低了 LPS 诱导的核因子κB(NF-κB)和 p38 丝裂原活化蛋白激酶(p38 MAPKs)的激活以及活性氧(ROS)的产生。综上所述,二苯并庚烷抑制 LPS 诱导的 NO 和 PGE2 产生可能是由于抑制了 NF-κB 和 p38 MAPK 信号通路,并且至少部分是通过抑制 ROS 的产生。因此,二苯并庚烷的这些作用可能有助于治疗伴有小胶质细胞激活的神经退行性疾病。

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