Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
J Alzheimers Dis. 2019;72(1):199-214. doi: 10.3233/JAD-190640.
Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive cognitive impairments. Vitegnoside is a flavonoid present in the medicinal plant Vitex negundo, widely used as a folk medicine in several Asian countries including China. It possesses several biological activities, including axon outgrowth, but no evidence is available on its effect on AD. Since no effective treatment is available to cure AD, the effect of vitegnoside on this disease was investigated. The human neuroblastoma SH-SY5Y cell line carrying the Swedish mutation that induces AβPP overexpression was used as an in vitro AD cell model. AβPP overexpression does not induce toxicity per se unless triggered by copper. Vitegnoside promoted neuroprotection through the improvement of cell viability, maintenance of cytomembrane integrity and nuclear homogeneity in these cells, but these effects were not observed in the copper-treated SH-SY5Y cells without AβPP overexpression used as the wild-type control, indicating that vitegnoside exerted neuroprotection under copper-triggered Aβ toxic conditions. Vitegnoside failed to decrease AβPP expression, Aβ40/42 levels, and oxidative stress due to copper-induced Aβ toxicity. However, its administration protected the mitochondrial function and restored the imbalance between pro-apoptotic and anti-apoptotic proteins. Additionally, vitegnoside inactivated p38 MAPK/MK2, JNK/c-Jun, and downstream NF-κB inflammatory transductions. Furthermore, the inactivation of p38 MAPK/JNK signaling contributed to vitegnoside-mediated neuroprotection resulting from pharmacological inhibition of p38 MAPK/JNK and in silico interaction prediction. Our study revealed the neuroprotective effect of vitegnoside and its potential mechanisms against copper-induced Aβ neurotoxicity. These findings highlighted the potential therapeutic effect of vitegnoside against AD progression.
阿尔茨海默病（AD）是一种慢性神经退行性疾病，其特征是进行性认知障碍。牡荆苷是马鞭草科植物牡荆中的一种类黄酮，广泛用作包括中国在内的几个亚洲国家的民间药物。它具有多种生物活性，包括轴突生长，但尚无其对 AD 影响的证据。由于没有有效的治疗方法可以治愈 AD，因此研究了牡荆苷对这种疾病的作用。使用携带诱导 AβPP 过表达的瑞典突变的人神经母细胞瘤 SH-SY5Y 细胞系作为体外 AD 细胞模型。AβPP 过表达本身不会引起毒性，除非被铜触发。牡荆苷通过提高细胞活力、维持细胞内膜完整性和核匀质性来促进神经保护，但在没有 AβPP 过表达的铜处理 SH-SY5Y 细胞（用作野生型对照）中未观察到这些作用，表明牡荆苷在铜触发的 Aβ 毒性条件下发挥神经保护作用。牡荆苷未能降低 AβPP 表达、Aβ40/42 水平和铜诱导的 Aβ 毒性引起的氧化应激。然而，它的给药保护了线粒体功能并恢复了促凋亡和抗凋亡蛋白之间的失衡。此外，牡荆苷使 p38 MAPK/MK2、JNK/c-Jun 和下游 NF-κB 炎症转导失活。此外，p38 MAPK/JNK 信号的失活有助于牡荆苷介导的神经保护，这是通过药理学抑制 p38 MAPK/JNK 和计算相互作用预测实现的。我们的研究揭示了牡荆苷对铜诱导的 Aβ 神经毒性的神经保护作用及其潜在机制。这些发现强调了牡荆苷对 AD 进展的潜在治疗作用。
