Abstract：
Copper-related reactive oxygen species (ROS) formation can lead to neuropathologic degradation associated with Alzheimer\'s disease (AD) according to amyloid cascade hypothesis. A complexing agent that can selectively chelate with copper ions and capture copper ions from the complex formed by copper ions and amyloid-β (Cu - Aβ complex) may be available in reducing ROS formation. Herein, we described applications of guluronic acid (GA), a natural oligosaccharide complexing agent obtained from enzymatic hydrolysis of brown algae, in reducing copper-related ROS formation. UV-vis absorption spectra demonstrated the coordination between GA and Cu(II). Ascorbic acid consumption and coumarin-3-carboxylic acid fluorescence assays confirmed the viability of GA in reducing ROS formation in solutions containing other metal ions and Aβ. Fluorescence kinetics, DPPH radical clearance and high resolution X - ray photoelectron spectroscopy results revealed the reductivity of GA. Human liver hepatocellular carcinoma (HepG2) cell viability demonstrated the biocompatibility of GA at concentrations lower than 320 μM. Cytotoxic results of human neuroblastoma (SH-SY5Y) cells verified that GA can inhibit copper-related ROS damage in neuronal cells. Our findings, combined with the advantages of marine drugs, make GA a promising candidate in reducing copper-related ROS formation associated with AD therapy.
摘要：
根据淀粉样蛋白级联假说,铜相关的活性氧(ROS)形成可导致与阿尔茨海默病(AD)相关的神经病理学降解。可以选择性地与铜离子螯合并从由铜离子和淀粉样蛋白-β形成的络合物(Cu-Aβ络合物)捕获铜离子的络合剂可用于减少ROS形成。在这里，我们描述了古洛糖醛酸(GA)的应用，从褐藻的酶水解获得的天然寡糖络合剂，减少与铜相关的ROS形成。UV-vis吸收光谱表明GA与Cu（II）之间的配位。抗坏血酸消耗和香豆素-3-羧酸荧光测定证实了GA在减少含有其他金属离子和Aβ的溶液中ROS形成方面的活力。荧光动力学,DPPH自由基清除和高分辨率X射线光电子能谱结果揭示了GA的还原性。人肝细胞癌（HepG2）细胞的生存力证明了浓度低于320μM的GA的生物相容性。人神经母细胞瘤（SH-SY5Y）细胞的细胞毒性结果验证了GA可以抑制神经元细胞中铜相关的ROS损伤。我们的发现,结合海洋药物的优势，使GA成为减少与AD治疗相关的铜相关ROS形成的有希望的候选物。
