State Key Laboratory of Biobased Materials and Green Papermaking, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong 250353, PR China.
State Key Laboratory of Biobased Materials and Green Papermaking, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong 250353, PR China.
J Inorg Biochem. 2023 Aug;245:112252. doi: 10.1016/j.jinorgbio.2023.112252. Epub 2023 May 6.
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.
铜相关的活性氧（ROS）形成可导致与阿尔茨海默病（AD）相关的神经病理退化，这是根据淀粉样蛋白级联假说得出的。一种络合剂，可以选择性地与铜离子络合，并从铜离子和淀粉样β（Cu-Aβ 复合物）形成的复合物中捕获铜离子，可能有助于减少 ROS 的形成。在此，我们描述了从褐藻酶解产物中获得的天然寡糖络合剂——古洛糖醛酸（GA）在减少铜相关 ROS 形成方面的应用。紫外可见吸收光谱证明了 GA 与 Cu(II) 的配位。抗坏血酸消耗和香豆素-3-羧酸荧光分析证实了 GA 在含有其他金属离子和 Aβ 的溶液中减少 ROS 形成的能力。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。人肝癌细胞（HepG2）活力研究表明，GA 在低于 320 μM 的浓度下具有生物相容性。人神经母细胞瘤（SH-SY5Y）细胞的细胞毒性结果证实，GA 可以抑制神经元细胞中与铜相关的 ROS 损伤。我们的研究结果结合海洋药物的优势，使 GA 成为治疗 AD 中减少铜相关 ROS 形成的有前途的候选药物。
