Design, Synthesis, and Biological Evaluation of Oligosaccharides Derived from Pleurotus ostreatus Polysaccharide as Potential Neuroprotective Agents

神经保护 化学 神经退行性变 生物化学 低聚糖 药理学 免疫印迹 生物活性 多糖 细胞凋亡 信号转导 结构-活动关系 程序性细胞死亡 作用机理
作者
Liuya Wang,He Wang,Huiqing Sun,Matthieu Sollogoub,Zhenyuan Zhu,Yongmin Zhang
出处
期刊:Journal of Medicinal Chemistry [American Chemical Society]
卷期号:69 (4): 4711-4725
标识
DOI:10.1021/acs.jmedchem.5c03324
摘要

Neurodegeneration has attracted considerable attention due to its extensive damage to the nervous system and broad impact on the population. Studies have shown that fungal polysaccharides, particularly those from mushrooms, have neuroprotective effects. POP-W with this effect was reported by our team. To understand its structure-activity relationship, three oligosaccharides derived from the branched part of POP-W were synthesized and characterized. H2O2-induced PC12 cell injury was selected as a model in this study. The biological tests showed that all three synthesized oligosaccharides were nontoxic and exhibited protective effects on H2O2-injured PC12 cells. Based on enzymatic activity assays and apoptosis analysis, the oligosaccharide C showed the best therapeutic effect. Further Western blot experiments confirmed that compound C brought neuroprotective effects by regulating Bcl-2/BAX and PI3K/Akt signaling pathways. These results demonstrate that oligosaccharide C possesses strong neuroprotective activity and may serve as a promising lead compound for future neuroprotective agents.
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