(7R,8S)-Dehydrodiconiferyl Alcohol Suppresses Lipopolysaccharide-Induced Inflammatory Responses in BV2 Microglia by Inhibiting MAPK Signaling
(7R,8S)-Dehydrodiconiferyl Alcohol Suppresses Lipopolysaccharide-Induced Inflammatory Responses in BV2 Microglia by Inhibiting MAPK Signaling
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(7R,8S)-脱氢二松醇通过抑制 MAPK 信号传导来抑制 BV2 小胶质细胞中脂多糖诱导的炎症反应
DOI：
10.1007/s11064-016-1870-8
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发表时间：
2016-07-01
影响因子：
4.4
通讯作者：
Liu, Xin-Hua
中科院分区：
文献类型：
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作者：
Liu, Si-Yu;Xu, Peng;Liu, Xin-Hua
(7R从华山铁线莲（Clematis armandii）的干茎中分离得到一种木脂素类化合物-脱氢双子叶醇（DDA），它在体外具有潜在的抗炎活性。在本研究中，我们研究了DDA对脂多糖（LPS）介导的小鼠BV 2小胶质细胞炎症反应的影响和可能的机制。结果显示，非毒性浓度（6.25-25 μM）的DDA以浓度依赖性方式显著抑制LPS诱导的一氧化氮生成、诱导型一氧化氮合酶和环氧合酶-2的表达以及炎症因子（包括肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β和IL-6）的释放。此外，DDA时间和浓度依赖性地减弱LPS诱导的c-Jun N-末端激酶1/2（JNK）的磷酸化，但不减弱蛋白激酶B、p38或细胞外信号调节激酶1/2。此外，DDA通过抑制NF-κB p65的磷酸化和核转位，显著抑制LPS介导的核因子-κB（NF-κB）活化。总的来说，我们的结果表明，DDA至少部分地通过抑制NF-κB活化和调节JNK信号传导来抑制BV 2细胞中LPS刺激的炎症反应。
(7R,8S)-Dehydrodiconiferyl alcohol (DDA), a lignan isolated from the dried stems ofClematis armandii, has been found to exert potential anti-inflammatory activity in vitro. In the present study, we investigated the effects and possible mechanisms of DDA on lipopolysaccharide (LPS)-mediated inflammatory response in murine BV2 microglia. Our results revealed that non-toxic concentrations (6.25–25 μM) of DDA markedly suppressed LPS-induced production of nitric oxide, expression of inducible nitric oxide synthase and cyclooxygenase-2, and release of inflammatory factors, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in a concentration dependent manner. In addition, DDA time- and concentration-dependently attenuated LPS-induced phosphorylation of c-Jun N-terminal kinase 1/2 (JNK), but not protein kinase B, p38, or extracellular signal-regulated kinase 1/2. Moreover, DDA significantly suppress LPS-mediated nuclear factor-κB (NF-κB) activation by inhibiting phosphorylation and nuclear translocation of NF-κB p65. Collectively, our results demonstrated that DDA inhibited LPS-stimulated inflammatory response in BV2 cell, at least in part, through inhibition of NF-κB activation and modulation of JNK signaling.