Lee Heasuk, Kim Young Ok, Kim Hocheol, Kim Sun Yeou, Noh Hae Sook, Kang Sang Soo, Cho Gyeong Jae, Choi Wan Sung, Suk Kyoungho
Department of Anatomy and Neurobiology, Research Institute of Natural Science, Gyeongsang National University College of Medicine, 92 Chilam-dong, Jinju, Kyungnam 660-751, Korea.
FASEB J. 2003 Oct;17(13):1943-4. doi: 10.1096/fj.03-0057fje. Epub 2003 Aug 1.
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.
汉黄芩素（5,7 - 二羟基 - 8 - 甲氧基黄酮）是一种源自药用植物黄芩根的黄酮类化合物，先前已证明其在包括巨噬细胞在内的多种细胞类型中具有抗炎活性。在本研究中，我们发现汉黄芩素是一种来自天然来源的强效神经保护剂。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 - 1β和一氧化氮（NO）的产生，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中诱导型一氧化氮合酶（iNOS）的诱导和核因子 - κB（NF - κB）的激活来抑制NO的产生。汉黄芩素对小胶质细胞炎症激活的抑制导致其对共培养的PC12细胞的细胞毒性降低，这支持了汉黄芩素在体外的神经保护作用。使用两种实验性脑损伤模型在体内进一步证明了汉黄芩素的神经保护作用；四血管闭塞引起的短暂性全脑缺血和全身注射海藻酸引起的兴奋性毒性损伤。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发挥神经保护作用，并且这种神经保护作用与抑制小胶质细胞的炎症激活有关。在全脑缺血模型中，汉黄芩素降低了海马中iNOS和TNF - α等炎症介质的诱导，在海藻酸注射模型中，通过小胶质细胞特异性异凝集素B4染色判断，汉黄芩素显著下调了小胶质细胞的激活。综上所述，我们的结果表明汉黄芩素通过抑制小胶质细胞激活发挥其神经保护作用，而小胶质细胞激活是神经退行性疾病致病性炎症反应的关键组成部分。当前研究强调了药用植物及其成分作为新型神经保护药物开发的宝贵来源的重要性。
