Herbacetin inhibits inducible nitric oxide synthase via JNK and nuclear factor-κB in LPS-stimulated RAW264.7 cells
Herbacetin inhibits inducible nitric oxide synthase via JNK and nuclear factor-κB in LPS-stimulated RAW264.7 cells
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DOI：
10.1016/j.ejphar.2015.08.032
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发表时间：
2015-10-15
影响因子：
5
通讯作者：
Soh, Yunjo
中科院分区：
文献类型：
--
作者：
Li, Liang;Sapkota, Mahesh;Soh, Yunjo
Herbacetin（3，4 '，5，7，8-pentahydroxyflavone）是黄酮类化合物中的一种活性黄酮醇化合物，已被证明可诱导HepG 2细胞凋亡并抑制肝细胞生长因子诱导的人乳腺癌MDA-MB-231细胞的运动。然而，Herbacetin的抗炎机制尚未研究。在这项研究中，我们研究了脂多糖（LPS）刺激的RAW264.7巨噬细胞的炎症反应后，用不同浓度的Herbacetin预处理。我们发现，Herbacetin减少一氧化氮（NO）的生产在LPS诱导的RAW 264.7和小鼠骨髓来源的巨噬细胞。此外，Herbacetin抑制LPS诱导的RAW264.7细胞诱导型一氧化氮合酶mRNA和蛋白的表达。Herbacetin治疗减少了促炎细胞因子的释放，包括TNF-α和IL-1 β。此外，Herbacetin抑制JNK激酶和核因子-κ B的活性，参与NO的产生的信号分子。使用Bay 11-7082（抑制性κ B激酶2抑制剂）和促分裂原活化蛋白激酶（MAPK）抑制剂（SB 203580用于p38，SP 600125用于JNK，PD 98059用于ERK）的细胞信号传导分析表明，LPS通过激活JNK和NF-κ B途径而不是p38和ERK途径诱导iNOS表达。这些结果表明，Herbacetin通过抑制LPS诱导的JNK和NF-κ B信号通路以及减少促炎细胞因子和介质的产生来发挥抗炎作用。(C)2015 Elsevier B. V.版权所有。
Herbacetin (3,4',5,7,8-pentahydroxyflavone), an active flavonol compound within flavonoid, has been shown to induce apoptosis in HepG2 cells and suppress hepatocyte growth factor-induced motility of human breast cancer MDA-MB-231 cells. However, the anti-inflammatory mechanisms of Herbacetin have not been researched. In this study, we examined the inflammatory responses stimulated by lipopolysaccharide (LPS) in RAW264.7 macrophage cells after pretreatment with different concentrations of Herbacetin. We found that Herbacetin decreased nitric oxide (NO) production in LPS-induced RAW264.7 and mouse bone marrow-derived macrophages. In addition, Herbacetin inhibited the LPS-induced expression of inducible nitric oxide synthase mRNA and protein in RAW264.7 cells. Treatment with Herbacetin decreased the release of proinflammatory cytokines, including TNF-alpha and IL-1 beta. Moreover, Herbacetin inhibited the activity of JNK kinase and nuclear factor-kappa B, signaling molecules involved in NO production. Cell signaling analysis using Bay 11-7082 (an inhibitory kappa B kinase 2 inhibitor) and mitogen-activated protein kinase (MAPK) inhibitors (SB203580 for p38, SP600125 for JNK, and PD 98059 for ERK) suggested that LPS induced iNOS expression via activation of the JNK and NF-kappa B pathway, but not the p38 and ERK pathway. These findings suggest that Herbacetin exerts an anti-inflammatory effect through suppression of LPS-induced JNK and NF-kappa B signaling pathways and diminished production of proinflammatory cytokines and mediators. (C) 2015 Elsevier B.V. All rights reserved.