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首页> 外文期刊>International immunopharmacology >Sappanone A exhibits anti-inflammatory effects via modulation of Nrf2 and NF-kappa B
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Sappanone A exhibits anti-inflammatory effects via modulation of Nrf2 and NF-kappa B

机译：Sappanone A通过调节Nrf2和NF-κB表现出抗炎作用

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摘要

Homoisofiavonoids constitute a small class of natural products. In the present study, we investigated the anti-inflammatory effect of sappanone A (SPNA), a homoisoflavanone that is isolated from the heartwood of Caesalpinia sappan (Leguminosae), in murine macrophages. SPNA inhibited the production of nitric oxide (NO), prostaglandin E-2 (PGE(2)) and interleuldn-6 (IL-6) as well as the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and IL-6 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Moreover, SPNA protected C57BL/6 mice from LPS-induced mortality. Treatment of RAW264.7 cells with SPNA induced heme oxygenase (HO)-1 protein and mRNA expression and increased nuclear translocation of the nuclear factor-E2-related factor 2 (Nrf2) as well as the expression of Nrf2 target genes such as NAD(P)H:quinone oxidoreductase 1 (NQO1). Knockdown of Nrf2 by siRNA blocked SPNA-mediated HO-1 induction. SB203580, p38 mitogen-activated protein kinase (MAPK) inhibitor, blocked SPNA-induced HO-1 expression and nuclear translocation of Nrf2, suggesting that SPNA induces HO-1 expression by activating Nrf2 through the p38 MAPK pathway. Consistent with the notion that the Nrf2/H0-1 pathway has anti-inflammatory properties, inhibiting HO-1 significantly abrogated the anti-inflammatory effects of SPNA in LPS-stimulated RAW264.7 cells. Moreover, SPNA suppressed LPS-induced nuclear factor kappa B (NF-kappa B) activation via inhibiting Ser 536 phosphorylation and transcriptional activity of RelA/p65 subunit of NF-kappa B. Taken together, these findings suggest that SPNA exerts its anti-inflammatory effect by modulating the Nrf2 and NF-kappa B pathways, and may be a valuable compound,to prevent or treat inflammatory diseases. (C) 2015 Elsevier B.V. All lights reserved.
机译：同型异黄酮类化合物是一小类天然产物。在本研究中，我们调查了鼠肝巨噬细胞中沙丁鱼（Sesanpinia sappan（Leguminosae）心木中分离出的一种高异黄烷酮——Sappanone A（SPNA）的抗炎作用。 SPNA抑制一氧化氮（NO），前列腺素E-2（PGE（2））和interleuldn-6（IL-6）的产生，以及诱导型一氧化氮合酶（iNOS），环氧合酶2（COX- 2）和脂多糖（LPS）刺激的RAW264.7细胞中的IL-6。此外，SPNA保护C57BL / 6小鼠免受LPS诱导的死亡。 SPNA诱导RAW264.7细胞的血红素加氧酶（HO）-1蛋白和mRNA表达并增加核因子E2相关因子2（Nrf2）的核易位以及Nrf2靶基因如NAD（ P）H：醌氧化还原酶1（NQO1）。 siRNA抑制Nrf2阻断SPNA介导的HO-1诱导。 SB203580，p38丝裂原激活蛋白激酶（MAPK）抑制剂，阻断SPNA诱导的HO-1表达和Nrf2的核易位，表明SPNA通过通过p38 MAPK途径激活Nrf2诱导HO-1表达。与Nrf2 / H0-1途径具有抗炎特性的观点一致，抑制HO-1可以显着废除SPNA在LPS刺激的RAW264.7细胞中的抗炎作用。此外，SPNA通过抑制NF-κBRelA / p65亚基的Ser 536磷酸化和转录活性，抑制LPS诱导的核因子κB（NF-κB）活化。综上所述，这些发现表明SPNA具有抗炎作用。通过调节Nrf2和NF-κB途径发挥作用，可能是预防或治疗炎性疾病的有价值的化合物。 （C）2015 Elsevier B.V.保留所有照明。

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