College of Jiamusi, Heilongjiang University of Chinese Medicine, Jiamusi, Heilongjiang, China.
Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin, China.
Cell Mol Neurobiol. 2018 Mar;38(2):549-557. doi: 10.1007/s10571-017-0519-8. Epub 2017 Jul 11.
Senile plaque accumulation and neurofibrillary tangles are primary characteristics of Alzheimer's disease. We aimed to assess the protective functions of naringenin against β-amyloid protein fragment 25-35 (Aβ)-caused nerve damage in differentiated PC12 cells, and study the potential mechanisms. We evaluated cell viability and apoptosis using the 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) test and flow cytometry, respectively. Moreover, we measured protein kinase B (Akt), glycogen synthase kinase-3β (GSK-3β), and caspase-3 activity via western blotting and RT-PCR. We found that naringenin protected cell against Aβ-caused nerve damage by increasing cell viability, promoting Akt and GSK3β activation, and inhibiting cell apoptosis and caspase-3 activity. However, treatment with the estrogen receptor (ER) antagonist ICI182, 780 or phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 suppressed the effects of naringenin. Our results suggested that naringenin could effectively suppress Aβ-caused nerve damage in PC12 cells by regulating the ER and PI3K/Akt pathways.
老年斑堆积和神经原纤维缠结是阿尔茨海默病的主要特征。我们旨在评估柚皮素对β-淀粉样蛋白片段 25-35（Aβ）引起的分化 PC12 细胞神经损伤的保护作用，并研究其潜在机制。我们分别使用 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）试验和流式细胞术评估细胞活力和细胞凋亡。此外，我们通过 Western blot 和 RT-PCR 测量蛋白激酶 B（Akt）、糖原合成酶激酶-3β（GSK-3β）和半胱氨酸天冬氨酸蛋白酶-3（caspase-3）的活性。我们发现，柚皮素通过增加细胞活力、促进 Akt 和 GSK3β 的激活、抑制细胞凋亡和 caspase-3 活性，来保护细胞免受 Aβ 引起的神经损伤。然而，用雌激素受体（ER）拮抗剂 ICI182,780 或磷脂酰肌醇-3-激酶（PI3K）抑制剂 LY294002 处理则抑制了柚皮素的作用。我们的结果表明，柚皮素可以通过调节 ER 和 PI3K/Akt 途径有效抑制 PC12 细胞中的 Aβ 引起的神经损伤。
