Cornuside Suppresses Lipopolysaccharide-Induced Inflammatory Mediators by Inhibiting Nuclear Factor-Kappa B Activation in RAW 264.7 Macrophages
Cornuside Suppresses Lipopolysaccharide-Induced Inflammatory Mediators by Inhibiting Nuclear Factor-Kappa B Activation in RAW 264.7 Macrophages
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Cornusside 通过抑制 RAW 264.7 巨噬细胞中核因子 Kappa B 的激活来抑制脂多糖诱导的炎症介质
DOI：
10.1248/bpb.34.959
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发表时间：
2011-07-01
影响因子：
2
通讯作者：
Yan, Guang Hai
中科院分区：
文献类型：
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作者：
Cuoi, Yun Ho;Jin, Guang Yu;Yan, Guang Hai
山茱萸苷是从山茱萸（Cornus officinalis S-1 EB）果实中分离得到的一种开环环烯醚萜苷类化合物。et Zucc.山茱萸苷具有免疫调节和抗炎活性。然而，角苷在炎症中的作用和机制尚未完全表征。因此，本研究的目的是检查是否cornuside抑制脂多糖（LPS）刺激的RAW 264.7巨噬细胞的炎症反应。山茱萸苷显著抑制LPS诱导的一氧化氮、前列腺素E-2、肿瘤坏死因子-α、白细胞介素-6（IL-6）和IL-1 β的产生。山茱萸苷还能降低诱导型一氧化氮合酶（iNOS）和环氧合酶-2（考克斯-2）的mRNA和蛋白表达。此外，山茱萸苷显着减弱LPS刺激的磷酸化和抑制性κ B-α的降解和随后的核因子-κ B（NF-κ B）的p65亚基的核转位。山茱萸苷还降低了细胞外信号相关激酶（ERK 1/2）、p38和c-Jun N-末端激酶（JNK 1/2）的磷酸化。这些结果表明，角苷的抗炎特性与下调iNOS和考克斯-2有关，这是由于NF-κ B抑制以及ERK 1/2、p38和JNK 1/2磷酸化的负性调节。
Cornuside, a secoiridoid glucoside compound, was isolated from the fruit of Cornus officinalis S-1EB. et Zucc. Cornuside has been reported to possess immunomodulatory and anti-inflammatory activities. However, the effects and mechanism of action of cornuside in inflammation have not been fully characterized. The present study was therefore designed to examine whether cornuside suppresses inflammatory response in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Cornuside significantly inhibited the LPS-induced production of nitric oxide, prostaglandin E-2, tumor necrosis factor-alpha, interleukin-6 (IL-6), and IL-1beta. The mRNA and protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were also decreased by cornuside. Furthermore, cornuside significantly attenuated the LPS-stimulated phosphorylation and degradation of inhibitory kappa B-alpha and the subsequent translocation of the p65 subunit of nuclear factor-kappa B (NF-kappa B) to the nucleus. Cornuside also reduced the phosphorylations of extracellular-signal-related kinase (ERK 1/2), p38, and c-Jun N-terminal kinase (JNK1/2). These results suggest that the anti-inflammatory property of cornuside is related to the downregulations of iNOS and COX-2 due to NF-kappa B inhibition as well as the negative regulation of ERK1/2, p38, and JNK1/2 phosphorylations in RAW 264.7 cells.