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海带正己烷提取物通过抑制 NF-κB 通路对脂多糖刺激的 RAW264.7 巨噬细胞发挥抗炎作用。

Hexane fraction from Laminaria japonica exerts anti-inflammatory effects on lipopolysaccharide-stimulated RAW 264.7 macrophages via inhibiting NF-kappaB pathway.

机构信息

Department of Food Science and Nutrition, Pukyong National University, 599-1, Daeyeon-dong, Nam-gu, Busan, 608-737, South Korea.

出版信息

Eur J Nutr. 2013 Feb;52(1):409-21. doi: 10.1007/s00394-012-0345-1. Epub 2012 Apr 5.

DOI:10.1007/s00394-012-0345-1
PMID:22476925
Abstract

PURPOSE

Laminaria japonica is a representative marine brown alga used as a culinary item in East Asia. L. japonica extract was shown to exert various biological activities; however, its anti-inflammatory activity has not been reported. The aim of this study is to investigate the molecular mechanisms underlying its anti-inflammatory action.

METHODS

Anti-inflammatory mechanisms of L. japonica n-hexane fraction (LHF) were assessed using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. An anti-inflammatory compound isolated from LHF by reverse-phase chromatography was identified using nuclear magnetic resonance (NMR) spectroscopy.

RESULTS

Our results indicate that LHF significantly inhibited LPS-stimulated nitric oxide (NO) and prostaglandin E(2) (PGE(2)) secretion in a dose-dependent manner and suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) with no cytotoxicity. As results, levels of pro-inflammatory cytokines were significantly reduced by pretreatment of LHF in LPS-stimulated RAW 264.7 cells. Treatment of LHF strongly suppressed nuclear factor-κB (NF-κB) promoter-driven expression and nuclear translocation of NF-κB by preventing proteolytic degradation of inhibitor of κB (IκB)-α in LPS-stimulated RAW 264.7 cells. Moreover, LHF inhibited the phosphorylation of Akt and mitogen-activated protein kinase (MAPK) in LPS-stimulated RAW 264.7 cells. One of the anti-inflammatory compounds was isolated from LHF and identified as fucoxanthin.

CONCLUSIONS

These results indicate that the LHF-mediated inhibition of NO and PGE(2) secretion in LPS-stimulated macrophages is regulated by NF-κB inactivation through inhibition of IκB-α, MAPKs, and Akt phosphorylation. LHF may be considered as a functional food candidate for the prevention or treatment of inflammatory diseases.

摘要

目的

裙带菜是东亚地区的一种代表性海洋褐藻,可作为食用材料。裙带菜提取物具有多种生物活性,但尚未有关于其抗炎活性的报道。本研究旨在探讨其抗炎作用的分子机制。

方法

采用脂多糖(LPS)刺激的 RAW 264.7 巨噬细胞评估裙带菜正己烷级分(LHF)的抗炎机制。通过反相色谱法从 LHF 中分离出一种抗炎化合物,并用核磁共振(NMR)光谱进行鉴定。

结果

结果表明,LHF 可显著抑制 LPS 刺激的 RAW 264.7 细胞一氧化氮(NO)和前列腺素 E2(PGE2)的分泌,呈剂量依赖性,并抑制诱导型一氧化氮合酶(iNOS)和环氧化酶-2(COX-2)的表达,且无细胞毒性。因此,LHF 预处理可显著降低 LPS 刺激的 RAW 264.7 细胞中促炎细胞因子的水平。LHF 可通过阻止 LPS 刺激的 RAW 264.7 细胞中 IκB-α的蛋白水解降解来强烈抑制 NF-κB 启动子驱动的表达和 NF-κB 的核转位。此外,LHF 抑制了 LPS 刺激的 RAW 264.7 细胞中 Akt 和丝裂原激活蛋白激酶(MAPK)的磷酸化。从 LHF 中分离出一种抗炎化合物,并鉴定为岩藻黄质。

结论

这些结果表明,LHF 介导的 LPS 刺激的巨噬细胞中 NO 和 PGE2 分泌的抑制作用是通过抑制 IκB-α、MAPKs 和 Akt 磷酸化来调节 NF-κB 失活的。LHF 可作为预防或治疗炎症性疾病的功能性食品候选物。

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