Kim Namkwon, Yoo Hyung-Seok, Ju Yeon-Joo, Oh Myung Sook, Lee Kyung-Tae, Inn Kyung-Soo, Kim Nam-Jung, Lee Jong Kil
Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.
Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea.
Biomol Ther (Seoul). 2018 Mar 1;26(2):210-217. doi: 10.4062/biomolther.2018.008.
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 E 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.
神经炎症是中枢神经系统针对各种促炎刺激的免疫反应。这种反应的异常激活会导致帕金森病、阿尔茨海默病和亨廷顿病等神经退行性疾病。因此，对异常神经炎症进行药理学调节被认为是改善神经退行性疾病的一种有前景的方法。在本研究中，我们评估了合成黄酮衍生物3'，4'-二羟基黄酮，研究其在BV2小胶质细胞和小鼠模型中的抗神经炎症活性。在BV2小胶质细胞中，3'，4'-二羟基黄酮成功抑制了BV2小胶质细胞中一氧化氮、前列腺素E等趋化因子以及肿瘤坏死因子α、白细胞介素1β和白细胞介素6等促炎细胞因子的产生。它还抑制了丝裂原活化蛋白激酶（MAPK）的磷酸化和核因子（NF）-κB的激活。这表明3'，4'-二羟基黄酮的抗炎活性可能与抑制促炎MAPK和NF-κB信号通路有关。在小鼠模型中也观察到了该化合物类似的抗神经炎症活性。这些发现表明，3'，4'-二羟基黄酮是治疗与小胶质细胞相关的神经炎症性疾病的潜在候选药物。
