Synthetic 3',4'-Dihydroxyflavone Exerts Anti-Neuroinflammatory Effects in BV2 Microglia and a Mouse Model.
Synthetic 3',4'-Dihydroxyflavone Exerts Anti-Neuroinflammatory Effects in BV2 Microglia and a Mouse Model.
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DOI：
10.4062/biomolther.2018.008
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发表时间：
2018-03-01
影响因子：
3.7
通讯作者：
Lee JK
中科院分区：
文献类型：
--
作者：
Kim N;Yoo HS;Ju YJ;Oh MS;Lee KT;Inn KS;Kim NJ;Lee JK
神经炎症是中枢神经系统内针对各种促炎刺激的免疫反应。这种反应的异常激活有助于神经变性疾病，例如帕金森病、阿尔茨海默病和亨廷顿病。因此，异常神经炎症的药物调节被认为是改善神经退行性疾病的有前途的方法。在这项研究中，我们评估了合成的黄酮衍生物3′，4 ′-二羟基黄酮，研究其在BV 2小胶质细胞和小鼠模型中的抗神经炎症活性。在BV 2小胶质细胞中，3′，4 ′-二羟基黄酮成功抑制了BV 2小胶质细胞中趋化因子（如一氧化氮和前列腺素E2）和促炎细胞因子（如肿瘤坏死因子α、白细胞介素1 β和白细胞介素6）的产生。抑制丝裂原活化蛋白激酶（MAPK）磷酸化和核因子（NF）-κB活化。提示3′，4 ′-二羟基黄酮的抗炎作用可能与抑制促炎MAPK和NF-κB信号通路有关。在小鼠模型中观察到该化合物的类似抗神经炎活性。这些结果表明，3′，4 ′-二羟基黄酮是一个潜在的候选药物治疗小胶质细胞相关的神经炎症性疾病。
Neuroinflammation is an immune response within the central nervous system against various proinflammatory stimuli. Abnormal activation of this response contributes to neurodegenerative diseases such as Parkinson disease, Alzheimer’s disease, and Huntington disease. Therefore, pharmacologic modulation of abnormal neuroinflammation is thought to be a promising approach to amelioration of neurodegenerative diseases. In this study, we evaluated the synthetic flavone derivative 3′,4′-dihydroxyflavone, investigating its anti-neuroinflammatory activity in BV2 microglial cells and in a mouse model. In BV2 microglial cells, 3′,4′-dihydroxyflavone successfully inhibited production of chemokines such as nitric oxide and prostaglandin E2 and proinflammatory cytokines such as tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in BV2 microglia. It also inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB activation. This indicates that the anti-inflammatory activities of 3′,4′-dihydroxyflavone might be related to suppression of the proinflammatory MAPK and NF-κB signaling pathways. Similar anti-neuroinflammatory activities of the compound were observed in the mouse model. These findings suggest that 3′,4′-dihydroxyflavone is a potential drug candidate for the treatment of microglia-related neuroinflammatory diseases.
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