Western Australian Biomedical Research Institute, Curtin University of Technology, Perth, Australia.
Mol Nutr Food Res. 2010 Jul;54 Suppl 2:S141-50. doi: 10.1002/mnfr.200900504.
Advanced glycation endproducts (AGEs) accumulate on protein deposits including the beta-amyloid plaques in Alzheimer's disease. AGEs interact with the "receptor for advanced glycation endproducts", and transmit their signals using intracellular reactive oxygen species as second messengers. Ultimately, AGEs induce the expression of a variety of pro-inflammatory markers including the tumor necrosis factor (TNF-alpha) and inducible nitric oxide (NO) synthase. Antioxidants that act intracellularly, including polyphenols, have been shown to scavenge these "signaling" reactive oxygen species, and thus perform in an anti-inflammatory capacity. This study tested the pure compounds apigenin and diosmetin as well as extracts from silymarin, uva ursi (bearberry) and green olive leaf for their ability to attenuate AGE-induced NO and TNF-alpha production. All five tested samples inhibited BSA-AGE-induced NO production in a dose-dependent manner. Apigenin and diosmetin were most potent, and exhibited EC(50) values approximately 10 microM. In contrast, TNF-alpha expression was only reduced by apigenin, diosmetin and silymarin; not by the bearberry and green olive leaf extracts. In addition, the silymarin and bearberry extracts caused significant cell death at concentrations >or=10 microg/mL and >or=50 microg/mL, respectively. In conclusion, we suggest that plant-derived polyphenols might offer therapeutic opportunities to delay the progression of AGE-mediated and receptor for advanced glycation endproducts-mediated neuro-inflammatory diseases including Alzheimer's disease.
糖基化终产物（AGEs）在蛋白质沉积物中积累，包括阿尔茨海默病中的β-淀粉样斑块。AGEs 与“晚期糖基化终产物受体”相互作用，并使用细胞内活性氧作为第二信使传递其信号。最终，AGEs 诱导多种促炎标志物的表达，包括肿瘤坏死因子（TNF-α）和诱导型一氧化氮合酶（iNOS）。已经表明，能够在细胞内发挥作用的抗氧化剂，包括多酚，能够清除这些“信号”活性氧，从而发挥抗炎作用。本研究测试了芹菜素和香叶木素以及水飞蓟素、熊果叶（越桔）和绿橄榄叶的提取物作为纯化合物，以测试它们减弱 AGE 诱导的 NO 和 TNF-α 产生的能力。所有五种测试样品均以剂量依赖性方式抑制 BSA-AGE 诱导的 NO 产生。芹菜素和香叶木素的作用最强，其 EC（50）值约为 10 μM。相比之下，只有芹菜素、香叶木素和水飞蓟素可以降低 TNF-α的表达，而熊果叶和绿橄榄叶提取物则不能。此外，水飞蓟素和熊果叶提取物在浓度大于或等于 10 μg/mL 和大于或等于 50 μg/mL 时会导致明显的细胞死亡。总之，我们认为植物来源的多酚可能为延迟 AGE 介导和晚期糖基化终产物受体介导的神经炎症性疾病（包括阿尔茨海默病）的进展提供治疗机会。
