Neuroprotective Effects of Ginsenoside Rf on Amyloid-β-Induced Neurotoxicity in vitro and in vivo
Neuroprotective Effects of Ginsenoside Rf on Amyloid-β-Induced Neurotoxicity in vitro and in vivo
复制标题
人参皂苷 Rf 对淀粉样蛋白-β 诱导的体外和体内神经毒性的神经保护作用。
DOI：
10.3233/jad-180251
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发表时间：
2018-01-01
影响因子：
4
通讯作者：
Dong, Zhifang
中科院分区：
文献类型：
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作者：
Du, Yehong;Fu, Min;Dong, Zhifang
阿尔茨海默病（AD）是一种以淀粉样β肽（A β）沉积为特征的神经退行性疾病。β积累导致神经元缠结、炎症、轴突损伤、突触丢失和神经元凋亡的形成。因此，降低A β水平应该对AD发挥神经保护作用。人参皂苷Rf是从三七中提取的一种有效成分，具有抗疲劳、抗伤害、抗氧化、抗炎等作用。然而，目前还不清楚是否有足够的Rf是有效的治疗AD。在这里，我们报道了在N2 A细胞中，C57 Rf可以显著减弱A β诱导的细胞凋亡，如通过线粒体膜电位的急剧增加和Ca 2+浓度、活性氧和活性半胱天冬酶-3表达的降低所反映的。同时，雷公藤多甙能减轻A β诱导的炎症反应，如降低IFN-γ和活性caspase 1的表达，增加IL-13的表达。此外，我们还发现Rf能够加速A β清除，并随后降低用人瑞典突变体APP 695（N2 A-APP）稳定转染的N2 A细胞中的A β水平。更重要的是，每日Rf治疗（20 mg/kg，i. p.）在整个实验中，在A β 42诱导的AD小鼠模型中显著改善了空间学习和记忆。综上所述，这些结果表明，在AD发展过程中，Rf可通过抗炎反应降低A β诱导的神经毒性和记忆力下降，表明Rf可能是治疗AD的潜在治疗剂。
Alzheimer's disease (AD) is a neurodegenerative disease characterized by the deposition of amyloid-beta peptides (A beta). A beta accumulation leads to the formation of neurofibrillary tangles, inflammation, axonal injury, synapse loss, and neuronal apoptosis. Thus, reducing A beta levels should exert a neuroprotective effect against AD. Ginsenoside Rf, an extract from Panax notoginseng, has potent anti-fatigue, anti-nociception, anti-oxidation, and anti-inflammation properties. However, it is unclear whether ginsenoside Rf is effective in the treatment of AD. Here, we reported that ginsenoside Rf could significantly attenuate A beta - induced apoptosis in N2A cells, as reflected by a dramatic increase in mitochondrial membrane potential and decrease in Ca2+ concentration, reactive oxygen species, and active caspase-3 expression. Meanwhile, ginsenoside Rf could alleviate the A beta - induced inflammation reaction, such as the decrease of interferon-gamma (IFN-gamma) and active caspase1 expression and the increase of interleukin-13. Furthermore, we also found that Rf is able to accelerate A beta clearance and subsequently reduces A beta level in N2A cells stably transfected with human Swedish mutant APP695 ( N2A-APP). More importantly, daily Rf treatment (20 mg/kg, i.p.) throughout the experiment dramatically improved spatial learning and memory in A beta 42-induced mouse model of AD. Taken together, these results indicate that ginsenoside Rf may decrease A beta - induced neurotoxicity and memory decline via anti-inflammatory response during AD development, suggesting that Rf may be a potential therapeutic agent for treating AD.