Zhou Rui, Shi Xu-Yang, Bi De-Cheng, Fang Wei-Shan, Wei Gao-Bin, Xu Xu
Shenzhen Key Laboratory of Marine Bioresources and Ecology, Collage of Life Science, Shenzhen University, Shenzhen 518060, China.
College of Life Science, Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen University, Shenzhen 518060, China.
Mar Drugs. 2015 Sep 16;13(9):5828-46. doi: 10.3390/md13095828.
Alginate from marine brown algae has been widely applied in biotechnology. In this work, the effects of alginate-derived oligosaccharide (AdO) on lipopolysaccharide (LPS)/β-amyloid (Aβ)-induced neuroinflammation and microglial phagocytosis of Aβ were studied. We found that pretreatment of BV2 microglia with AdO prior to LPS/Aβ stimulation led to a significant inhibition of production of nitric oxide (NO) and prostaglandin E₂ (PGE₂), expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and secretion of proinflammatory cytokines. We further demonstrated that AdO remarkably attenuated the LPS-activated overexpression of toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB in BV2 cells. In addition to the impressive inhibitory effect on neuroinflammation, we also found that AdO promoted the phagocytosis of Aβ through its interaction with TLR4 in microglia. Our results suggested that AdO exerted the inhibitory effect on neuroinflammation and the promotion effect on microglial phagocytosis, indicating its potential as a nutraceutical or therapeutic agent for neurodegenerative diseases, particularly Alzheimer's disease (AD).
来自海洋褐藻的藻酸盐已在生物技术中得到广泛应用。在这项研究中,我们研究了藻酸盐衍生的寡糖(AdO)对脂多糖(LPS)/β-淀粉样蛋白(Aβ)诱导的神经炎症以及小胶质细胞对Aβ的吞噬作用的影响。我们发现,在LPS/Aβ刺激之前用AdO预处理BV2小胶质细胞,可显著抑制一氧化氮(NO)和前列腺素E₂(PGE₂)的产生、诱导型一氧化氮合酶(iNOS)和环氧化酶-2(COX-2)的表达以及促炎细胞因子的分泌。我们进一步证明,AdO可显著减轻BV2细胞中LPS激活的Toll样受体4(TLR4)和核因子(NF)-κB的过表达。除了对神经炎症有显著的抑制作用外,我们还发现AdO通过与小胶质细胞中的TLR4相互作用促进了Aβ的吞噬作用。我们的结果表明,AdO对神经炎症具有抑制作用,对小胶质细胞吞噬作用具有促进作用,表明其作为神经退行性疾病,特别是阿尔茨海默病(AD)的营养保健品或治疗剂的潜力。