Xin Haolin, Cui Ying, An Zhongping, Yang Qian, Zou Xuan, Yu Ning
Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Department of Neurology, Nankai University, Huanhu Hospital Tianjin China
Tianjin University of Traditional Chinese Medicine Tianjin China.
RSC Adv. 2019 Oct 28;9(60):34735-34743. doi: 10.1039/c9ra03848e.
Glutamate is an excitatory neurotransmitter involved in neural function. Excess accumulation of intercellular glutamate leads to increasing concentration of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in neuronal cells. In this study, we investigated the antioxidant activity of several typical superior compounds among four neuronal cells, and determined the scavenging activity of free radicals. The assay was also carried out to compare the protective effect of glutamate-induced cell damage. Hierarchical clustering analysis was used to identify the common properties. Glutamate induced neurotoxicity and ROS production, suggesting glutamate cytotoxicity was related to oxidative stress and widely exists in different cell lines. Those screening compounds exhibited strong antioxidant ability, but low cytotoxicity to neuronal cells, acting as agents against neurodegenerative diseases. Finally, a hierarchical clustering analysis assay indicated that hyperoside and rutin hydrate are the most effective compounds for attenuating intercellular ROS levels. The results suggested the activity more or less relies on structure, rather than residues. These data generate new supporting ideas to remove intracellular ROS and the identified compounds serve as potential therapeutic agents in multiple neurological diseases.
谷氨酸是一种参与神经功能的兴奋性神经递质。细胞间谷氨酸的过量积累会导致神经元细胞中活性氧（ROS）和活性氮（RNS）浓度增加。在本研究中，我们研究了四种神经元细胞中几种典型优质化合物的抗氧化活性，并测定了自由基清除活性。还进行了实验以比较谷氨酸诱导的细胞损伤的保护作用。采用层次聚类分析来确定共同特性。谷氨酸诱导神经毒性和ROS产生，表明谷氨酸细胞毒性与氧化应激有关，并且广泛存在于不同细胞系中。那些筛选出的化合物表现出强大的抗氧化能力，但对神经元细胞的细胞毒性较低，可作为抗神经退行性疾病的药物。最后，层次聚类分析实验表明，金丝桃苷和芦丁水合物是降低细胞间ROS水平最有效的化合物。结果表明，活性或多或少依赖于结构，而不是残基。这些数据为清除细胞内ROS产生了新的支持观点，并且所鉴定的化合物可作为多种神经疾病的潜在治疗药物。
