Antiinflammatory effects of orientin-2"-O-galactopyranoside on lipopolysaccharide-stimulated microglia.
Antiinflammatory effects of orientin-2"-O-galactopyranoside on lipopolysaccharide-stimulated microglia.
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DOI：
10.1248/bpb.b14-00083
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发表时间：
2014-08
影响因子：
2
通讯作者：
Xiang Zhou;P. Gan;Lili Hao;L. Tao;J. Jia;Bo Gao;Jiang-yun Liu;L. Zheng;Xuechu Zhen
中科院分区：
文献类型：
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作者：
Xiang Zhou;P. Gan;Lili Hao;L. Tao;J. Jia;Bo Gao;Jiang-yun Liu;L. Zheng;Xuechu Zhen
小胶质细胞激活介导的神经炎症在阿尔茨海默病、帕金森病、多发性硬化症和人类免疫缺陷病毒(HIV)相关性痴呆等神经退行性疾病的发病机制中发挥着重要作用。抑制小胶质细胞的激活可能会减轻神经炎性条件下的神经变性。在本研究中，我们用基于细胞的方法比较了从金莲花中提取的三种黄酮类C-糖苷，以评估它们对小胶质细胞的抗炎作用。结果表明，冬凌草甲素-2“-O-半乳糖苷可显著抑制脂多糖刺激的小胶质细胞产生一氧化氮和肿瘤坏死因子-α。OGA还能显著抑制脂多糖诱导的肿瘤坏死因子α、白介素1β、诱导型一氧化氮合酶和环氧合酶2的表达，同时抑制核因子-κB的活化和细胞外信号调节激酶信号通路。此外，OGA还可减少脂多糖诱导的活性氧生成，这可能与激活BV-2小胶质细胞中的核因子-E2相关因子2(NRF2)/血红素氧合酶-1(HO-1)途径有关。此外，在共培养系统中，OGA降低了激活的小胶质细胞对HT-22神经母细胞瘤细胞的细胞毒作用。综上所述，本研究表明，HO-1介导的抑制NF-ERKB和κ信号转导通路的作用与OGA的抗神经炎症和神经保护作用密切相关。
Microglia activation-mediated neuroinflammation plays an important role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and human immunodeficiency virus (HIV)-associated dementia. Inhibition of microglia activation may alleviate neurodegeneration under neuroinflammatory conditions. In the present study, we compared three flavone C-glycosides extracted from Trollius chinensis BUNGE using a cell-based assay to evaluate their antiinflammatory effects on microglial cells. The results showed that orientin-2"-O-galactopyranoside (OGA) significantly inhibited the production of nitric oxide and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-stimulated microglial cells. OGA also markedly inhibited the LPS-induced expression of TNF-α, interleukin-1β, inducible nitric oxide (NO) synthase, and cyclooxygenase-2, which was accompanied by suppression of the activation of nuclear factor (NF)-κB and the extracellular signal-regulated kinase (ERK) signal pathway. In addition, OGA decreased LPS-induced reactive oxygen species generation, which appears to be related to the activation of the NF-E2-related factor2 (NRF2)/ heme oxygenase-1 (HO-1) pathway in BV-2 microglial cells. Furthermore, OGA reduced the cytotoxicity of activated microglia toward HT-22 neuroblastoma cells in a co-culture system. Taken together, the present study demonstrated that the induction of HO-1-mediated inhibition of the NF-κB and ERK pathways contributes significantly to the antineuroinflammatory and neuroprotective effects elicited by OGA.