Honokiol inhibits the inflammatory reaction during cerebral ischemia reperfusion by suppressing NF-κB activation and cytokine production of glial cells

Honokiol inhibits the inflammatory reaction during cerebral ischemia reperfusion by suppressing NF-κB activation and cytokine production of glial cells
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DOI:
10.1016/j.neulet.2012.11.052
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发表时间:
2013-02
影响因子:
2.5
通讯作者:
Peng Zhang;Xiao-yan Liu;Yuanjun Zhu;Shizhong Chen;Demin Zhou;Yinye Wang
Peng Zhang;Xiao-yan Liu;Yuanjun Zhu;Shizhong Chen;Demin Zhou;Yinye Wang
中科院分区:
医学4区
文献类型:
--
作者:
Peng Zhang;Xiao-yan Liu;Yuanjun Zhu;Shizhong Chen;Demin Zhou;Yinye Wang

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本研究旨在探讨神经保护剂和厚朴酚对脑缺血再灌注(IR)小鼠脑水肿的影响及其抗炎机制。厚朴酚(0.7 ~ 70μg/kg)可显著降低IR小鼠脑组织含水量和脑毛细血管伊文思蓝渗出量。和厚朴酚(0.1-10μM)显著降低原代培养的小胶质细胞核中NF-κB的p65亚基水平。0.01-10μM的小胶质细胞培养液及小胶质细胞和星形胶质细胞共培养液中的一氧化氮(NO)含量明显降低。和厚朴酚(0.01-10μM)可显著降低小胶质细胞培养液或共培养细胞培养液中TNF-α的水平。和厚朴酚(10μM)可降低小胶质细胞或星形胶质细胞培养基中的正常T细胞表达和分泌的调节激活(RANTES/CCL 5)蛋白水平。结论:和厚朴对脑缺血再灌注小鼠有明显的抗炎作用,其机制可能与抑制NF-κB的活化,从而抑制神经胶质细胞NO、TNF-α和RANTES/CCL 5等炎症因子的产生有关。这些结果为和厚朴的抗炎作用提供了证据,为缺血性卒中的潜在治疗提供了依据。
This study was designed to investigate the effects of honokiol, a neuroprotective agent, on cerebral edema in cerebral ischemia reperfusion (IR) mice and its mechanism of anti-inflammation. Honokiol (0.7–70μg/kg) significantly reduced brain water contents and decreased the exudation of Evans blue dye from brain capillaries in cerebral IR mice. Honokiol (0.1–10μM) significantly reduced the p65 subunit level of NF-κB in the nucleus of primary culture-microglia. It (0.01–10μM) evidently reduced nitric oxide (NO) level in the microglia culture medium and in the microglia and astrocytes coculture medium. Honokiol (0.01–10μM) significantly decreased the level of TNF-α in the microglia medium or coculture cell medium. Honokiol (10μM) decreased the level of Regulated upon Activation Normal T-cell Expressed and Secreted (RANTES/CCL5) protein in medium of microglia or astrocytes. In conclusion, Honokiol has a potent anti-inflammatory effect in cerebral ischemia-reperfusion mice and this effect might be attributed to its inhibition ability on the NF-κB activation, consequently blocking the production of inflammatory factors including: NO, tumor necrosis factor-α (TNF-α) and RANTES/CCL5 in glial cells. These results provide evidence for the anti-inflammatory effect of honokiol for the potential treatment of ischemic stroke.