Flavonoid wogonin from medicinal herb is neuroprotective by inhibiting inflammatory activation of microglia
Flavonoid wogonin from medicinal herb is neuroprotective by inhibiting inflammatory activation of microglia
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DOI：
10.1096/fj.03-0057fje
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发表时间：
2003-08-01
期刊：
影响因子：
4.8
通讯作者：
Suk, K
中科院分区：
文献类型：
--
作者：
Lee, H;Kim, YO;Suk, K
汉黄芩素（5，7-二羟基-8-甲氧基黄酮）是一种来源于药用植物黄芩根的黄酮类化合物，先前已显示在包括巨噬细胞在内的各种细胞类型中具有抗炎活性。在这项工作中，我们发现汉黄芩素是一种有效的神经保护剂，从天然来源。汉黄芩素通过减少脂多糖诱导的肿瘤坏死因子-α（TNF-α）、白细胞介素-1 β和一氧化氮（NO）的产生来抑制培养的脑小胶质细胞的炎症激活。汉黄芩素通过抑制小胶质细胞诱导型一氧化氮合酶（iNOS）的诱导和NF-κ B的活化来抑制NO的产生。汉黄芩素抑制小胶质细胞的炎症激活导致对共培养的PC 12细胞的小胶质细胞毒性降低，支持汉黄芩素在体外的神经保护作用。汉黄芩素的神经保护作用进一步证明在体内使用两个实验性脑损伤模型;短暂性全脑缺血四血管闭塞和兴奋性毒性损伤全身红藻氨酸注射。在这两种动物模型中，汉黄芩素通过减轻海马神经元的死亡来赋予神经保护作用，并且神经保护作用与抑制小胶质细胞的炎性活化相关。在全脑缺血模型中，汉黄芩素减少了海马神经元对炎症介质如iNOS和TNF-α的诱导，在红藻氨酸注射模型中，汉黄芩素显著下调了小胶质细胞活化，这通过小胶质细胞特异性isolectin B4染色来判断。总之，我们的研究结果表明，汉黄芩素发挥其神经保护作用，通过抑制小胶质细胞活化，这是一个重要组成部分的致病性炎症反应在神经退行性疾病。目前的研究强调了草药及其成分作为开发新型神经保护药物的宝贵来源的重要性。
Wogonin (5,7-dihydroxy-8-methoxyflavone), a flavonoid originated from the root of a medicinal herb Scutellaria baicalensis Georgi, has been previously shown to have anti-inflammatory activities in various cell types including macrophages. In this work, we have found that wogonin is a potent neuroprotector from natural source. Wogonin inhibited inflammatory activation of cultured brain microglia by diminishing lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta, and nitric oxide ( NO) production. Wogonin inhibited NO production by suppressing inducible NO synthase (iNOS) induction and NF-kappaB activation in microglia. Inhibition of inflammatory activation of microglia by wogonin led to the reduction in microglial cytotoxicity toward cocultured PC12 cells, supporting a neuroprotective role for wogonin in vitro. The neuroprotective effect of wogonin was further demonstrated in vivo using two experimental brain injury models; transient global ischemia by four-vessel occlusion and excitotoxic injury by systemic kainate injection. In both animal models, wogonin conferred neuroprotection by attenuating the death of hippocampal neurons, and the neuroprotective effect was associated with inhibition of the inflammatory activation of microglia. Hippocampal induction of inflammatory mediators such as iNOS and TNF-alpha was reduced by wogonin in the global ischemia model, and microglial activation was markedly down-regulated by wogonin in the kainate injection model as judged by microglia-specific isolectin B4 staining. Taken together, our results indicate that wogonin exerts its neuroprotective effect by inhibiting microglial activation, which is a critical component of pathogenic inflammatory responses in neurodegenerative diseases. The current study emphasizes the importance of medicinal herbs and their constituents as an invaluable source for the development of novel neuroprotective drugs.