Naringenin attenuates the release of pro-inflammatory mediators from lipopolysaccharide-stimulated BV2 microglia by inactivating nuclear factor-κB and inhibiting mitogen-activated protein kinases
Naringenin attenuates the release of pro-inflammatory mediators from lipopolysaccharide-stimulated BV2 microglia by inactivating nuclear factor-κB and inhibiting mitogen-activated protein kinases
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DOI：
10.3892/ijmm.2011.979
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发表时间：
2012-07-01
影响因子：
5.4
通讯作者：
Choi, Yung Hyun
中科院分区：
文献类型：
--
作者：
Park, Hye Young;Kim, Gi-Young;Choi, Yung Hyun
柚皮素是柑橘类水果和葡萄柚中含量最丰富的黄酮类化合物之一，据报道具有抗炎和抗肿瘤活性。然而，对柚皮素抗炎活性的细胞和分子机制知之甚少。在这项研究中，我们进行了一项调查，柚皮素对生产的脂多糖（LPS）诱导的促炎介质在BV 2小胶质细胞的抑制作用。我们发现在用LPS处理之前用柚皮素预处理以剂量依赖的方式显著抑制一氧化氮（NO）和前列腺素E-2（PGE（2））的过量产生。这种抑制作用与诱导型一氧化氮合酶（iNOS）和环氧化酶-2（考克斯-2）表达下调有关。柚皮素还通过抑制促炎细胞因子和趋化因子（包括白细胞介素-1 β（IL-1 β）、肿瘤坏死因子-α（TNF-α）和单核细胞趋化蛋白-1（MCP-1））的mRNA表达来减弱这些蛋白的产生。此外，柚皮素介导的BV 2细胞减毒的分子机制与抑制核因子-κ B（NF-κ B）p65亚基向细胞核的移位以及Akt和促分裂原活化蛋白激酶（MAPK）的磷酸化密切相关。这些发现表明，柚皮素可以通过抑制激活的BV 2小胶质细胞中的促炎通路来提供神经保护。
Naringenin, one of the most abundant flavonoids in citrus fruits and grapefruits, has been reported to exhibit anti-inflammatory and antitumor activities. However, the cellular and molecular mechanisms underlying the naringenin anti-inflammatory activity are poorly understood. In this study, we conducted an investigation of the inhibitory effects of naringenin on the production of lipopolysaccharide (LPS)-induced pro-inflammatory mediators in BV2 microglial cells. We found that pre-treatment with naringenin prior to treatment with LPS significantly inhibited excessive production of nitric oxide (NO) and prostaglandin E-2 (PGE(2)) in a dose-dependent manner. The inhibition was associated with downregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Naringenin also attenuated the production of pro-inflammatory cytokines and chemokines, including interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattractant protein-1 (MCP-1) by suppressing expression of m RNAs for these proteins. In addition, the molecular mechanism underlying naringenin-mediated attenuation in BV2 cells has a close relationship to suppressing translocation of the nuclear factor-kappa B (NF-kappa B) p65 subunit into the nucleus and the phosphorylation of Akt and mitogen-activated protein kinases (MAPKs). These findings suggest that naringenin may provide neuroprotection through suppression of pro-inflammatory pathways in activated BV2 microglial cells.