Che Hongxia, Du Lei, Cong Peixu, Tao Suyuan, Ding Ning, Wu Fengjuan, Xue Changhu, Xu Jie, Wang Yuming
1 College of Food Science and Engineering, Ocean University of China , Qingdao, China .
2 Division of Marine Life Science, Faculty of Fisheries Sciences, Hokkaido University , Hakodate, Japan .
J Med Food. 2017 Apr;20(4):392-402. doi: 10.1089/jmf.2016.3789.
Alzheimer's disease (AD) is a neurodegenerative disorder. Emerging evidence implicates β-amyloid (Aβ) plays a critical role in the progression of AD. In this study, we investigated the protective effect of cerebrosides obtained from sea cucumber against senescence-accelerated mouse prone 8 (SAMP8) mice in vivo. We also studied the effect of cerebrosides on Aβ-induced cytotoxicity on the rat pheochromocytoma cell (PC12) and the underlying molecular mechanisms. Cerebrosides ameliorated learning and memory deficits and the Aβ accumulation in demented mice, decreased the content of malondialdehyde (MDA), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG), 8-hydroxy-2'-deoxyguanosine (8-oxo-G), and nitric oxide (NO), and enhanced the superoxide dismutase (SOD) activity significantly. The neuroprotective effect of sea cucumber cerebrosides (SCC) was also verified in vitro: the cerebrosides increased the survival rate of PC12 cells, recovered the cellular morphology, downregulated the protein levels of Caspase-9, cleaved Caspase-3, total Caspase-3, and Bax, and upregulated the protein level of Bcl-2, revealing that cerebrosides could inhibit Aβ-induced cell apoptosis. The results showed the protective effect of SCC was regulated by the mitochondria-dependent apoptotic pathway. Our results provide a new approach to developing the marine organisms as functional foods for neuroprotection.
阿尔茨海默病（AD）是一种神经退行性疾病。新出现的证据表明β-淀粉样蛋白（Aβ）在AD的进展中起关键作用。在本研究中，我们在体内研究了从海参中提取的神经酰胺对衰老加速小鼠8型（SAMP8）的保护作用。我们还研究了神经酰胺对Aβ诱导的大鼠嗜铬细胞瘤细胞（PC12）细胞毒性的影响及其潜在的分子机制。神经酰胺改善了痴呆小鼠的学习和记忆缺陷以及Aβ积累，降低了丙二醛（MDA）、8-氧代-7,8-二氢-2'-脱氧鸟苷（8-OHdG）、8-羟基-2'-脱氧鸟苷（8-氧代-G）和一氧化氮（NO）的含量，并显著提高了超氧化物歧化酶（SOD）活性。海参神经酰胺（SCC）的神经保护作用在体外也得到了验证：神经酰胺提高了PC12细胞的存活率，恢复了细胞形态，下调了Caspase-9、裂解的Caspase-3、总Caspase-3和Bax的蛋白水平，并上调了Bcl-2的蛋白水平，表明神经酰胺可以抑制Aβ诱导的细胞凋亡。结果表明，SCC的保护作用是由线粒体依赖性凋亡途径调节的。我们的结果为开发海洋生物作为神经保护功能性食品提供了一种新方法。
