Fu Zheng, Yang Jiufang, Wei Yangji, Li Jingming
Center for Viticulture and Enology, College of Food Science and Nutritional Engineering, China Agricultural University, P. O. Box 301, Beijing 100083, China.
Food Funct. 2016 Feb;7(2):1014-23. doi: 10.1039/c5fo01124h.
Neuron apoptosis induced by β-amyloid (Aβ) is an important precipitating factor in the pathogenesis of Alzheimer's disease (AD). In the present study, the effects of piceatannol (PT) and pterostilbene (PS) against Aβ-induced apoptosis in PC12 cells were evaluated. PT and PS both showed observable anti-apoptosis activity. Increased cell viability, decreased apoptosis rate and declining intracellular ROS were observed after PT and PS treatment. For the signaling pathway, PT significantly promoted phosphorylation of Akt and Bad, further suppressed Bcl-2/Bax expression and inhibited cleavage of caspase-9, caspase-3 and PARP. PS promoted phosphorylation of Akt without affecting the other factors. The experimental results, for the first time, unambiguously suggested that PT showed a comprehensive protective effect against Aβ-induced apoptosis in PC12 cells via a novel PI3K/Akt/Bad signaling pathway and downstream mitochondria-mediated and caspase-dependent signaling pathway. Unlike PT, PS inhibited apoptosis against Aβ through a different PI3K/Akt signaling pathway in which the downstream targets need to be further investigated. The results also provide the basis for dietary intervention involved in the prevention and adjunctive therapy of AD.
β-淀粉样蛋白（Aβ）诱导的神经元凋亡是阿尔茨海默病（AD）发病机制中的一个重要促发因素。在本研究中，评估了白皮杉醇（PT）和紫檀芪（PS）对Aβ诱导的PC12细胞凋亡的影响。PT和PS均表现出明显的抗凋亡活性。PT和PS处理后，细胞活力增加、凋亡率降低且细胞内活性氧水平下降。对于信号通路，PT显著促进Akt和Bad的磷酸化，进一步抑制Bcl-2/Bax表达，并抑制caspase-9、caspase-3和PARP的裂解。PS促进Akt的磷酸化，而不影响其他因素。实验结果首次明确表明，PT通过一条新的PI3K/Akt/Bad信号通路以及下游线粒体介导的和caspase依赖的信号通路，对Aβ诱导的PC12细胞凋亡具有全面的保护作用。与PT不同，PS通过一条不同的PI3K/Akt信号通路抑制Aβ诱导的凋亡，其中下游靶点有待进一步研究。这些结果也为AD的预防和辅助治疗中的饮食干预提供了依据。
