Abstract：
Alzheimer\'s disease (AD) is a neurodegenerative disease characterized by memory loss and cognitive impairment. β-amyloid (Aβ) is one of the typical pathological features of AD, and its accumulation leads to neuronal death from oxidative stress. Here, we found that hederagenin (HG), a natural product, exhibits anti-tumor, anti-inflammatory, anti-depressant, anti-neurodegenerative biological activities. However, whether HG has anti-Aβ activity remains unclear. Based on the characteristics of HG, it is hypothesized that HG has biological activity against Aβ injury. Therefore, Aβ-injured SH-SY5Y cells were constructed, and the protective effect of HG against Aβ injury was further evaluated using C. elegans. The results showed that HG increased superoxide dismutase activity, effectively reduced Aβ-induced oxidative damage, and reduced apoptosis via the PI3 K/Akt signaling pathway. HG inhibited Aβ deposition and delayed senescence and paralysis in the C. elegans strain, CL4176. HG showed inhibitory effects on Aβ; therefore, more natural active products are expected to be applied in AD therapy.
摘要：
阿尔茨海默病(Alzheimer’sdisease,AD)是一种以记忆力减退和认知障碍为特征的神经退行性疾病。β-淀粉样蛋白(Aβ)是AD的典型病理特征之一。它的积累导致神经元因氧化应激而死亡。这里,我们发现海得拉素（HG），一种天然产物,表现出抗肿瘤，抗炎,抗抑郁药,抗神经退行性生物活性。然而,HG是否具有抗Aβ活性尚不清楚。基于HG的特点,假设HG具有抗Aβ损伤的生物学活性。因此,构建Aβ损伤的SH-SY5Y细胞,用秀丽隐杆线虫进一步评价HG对Aβ损伤的保护作用。结果表明，HG增加了超氧化物歧化酶的活性，有效减少Aβ诱导的氧化损伤，并通过PI3K/Akt信号通路减少细胞凋亡。HG抑制Aβ沉积，延缓秀丽隐杆线虫的衰老和麻痹，CL4176.HG对Aβ有抑制作用；因此，更多的天然活性产品有望应用于AD治疗。
