The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
Biomed Pharmacother. 2018 Jul;103:680-690. doi: 10.1016/j.biopha.2018.04.063. Epub 2018 Apr 24.
Age-related neuronal injury and oxidative damage are the predominant factors for neurodegenerative diseases like Alzheimer's disease (AD). The aim of this study was to explore whether chronic administration of d-galactose (d-gal) can cause neuronal injury and oxidative damage, and to investigate the neuroprotective and antioxidative effects of the active components (UPNO-1) from Korean pine nut (Pinus koraiensis). Two dosing regimens were designed, one for the evaluation of preventive effects in which the rats were simultaneously administrated d-gal and UPNO-1/fishoil for 12 weeks, the other for the evaluation of therapeutic effects in which the rats were given d-gal for 8 weeks before treated with UPNO-1/selegiline for 8 weeks. The experimental results demonstrated that chronic administration of d-gal produced histopathological changes and increased neuronal apoptosis, and decreased significantly the activities of T-AOC, T-SOD and CAT. Additionally, a comprehensive metabolic profiling of d-gal-treated rats was performed for the first time to investigate the metabolic disorders in the hippocampus, cortex and plasma, and a total of 32 annotated metabolites were significantly increased or decreased in the modeled rats. Major disturbed metabolic pathways were fatty acid, glycerolphospholipid and arachidonic acid metabolic pathways. UPNO-1 significantly diminished neuronal apoptosis, ameliorated histopathological findings, and increased the activities of T-SOD and CAT but not T-AOC. Furthermore, UPNO-1 attenuated the decreased plasma levels of 3-oxooctanoic acid, l-tryptophan, 12-hydroxyheptadecanoic acid, lysophosphatidylcholine (16:0) (LPC(16:0)), LPC(18:3) and LPC(18:1) in the modeled rats. These results illustrated the mechanisms of d-gal induced neurotoxicity and oxidative stress and proved the positive effects of UPNO-1 on preventing and treating d-gal-induced-aging rats.
年龄相关的神经元损伤和氧化损伤是阿尔茨海默病（AD）等神经退行性疾病的主要因素。本研究旨在探讨慢性给予半乳糖（d-gal）是否会导致神经元损伤和氧化应激，并研究来自红松（Pinus koraiensis）的活性成分（UPNO-1）的神经保护和抗氧化作用。设计了两种给药方案，一种用于评估预防作用，即同时给予 d-gal 和 UPNO-1/鱼油 12 周；另一种用于评估治疗作用，即给予 d-gal 8 周后，用 UPNO-1/司来吉兰治疗 8 周。实验结果表明，慢性给予 d-gal 可产生组织病理学变化，增加神经元凋亡，并显著降低 T-AOC、T-SOD 和 CAT 的活性。此外，首次对 d-gal 处理大鼠进行了全面代谢谱分析，以研究海马体、皮质和血浆中的代谢紊乱，模型大鼠中共有 32 种注释代谢物显著增加或减少。主要紊乱的代谢途径是脂肪酸、甘油磷脂和花生四烯酸代谢途径。UPNO-1 显著减少神经元凋亡，改善组织病理学发现，并增加 T-SOD 和 CAT 的活性，但不增加 T-AOC 的活性。此外，UPNO-1 可减轻模型大鼠血浆中 3-氧代辛酸、l-色氨酸、12-羟基十七烷酸、溶血磷脂酰胆碱（16:0）（LPC（16:0））、LPC（18:3）和 LPC（18:1）水平的降低。这些结果说明了 d-gal 诱导的神经毒性和氧化应激的机制，并证明了 UPNO-1 对预防和治疗 d-gal 诱导的衰老大鼠的积极作用。
