Zeng Gao-feng, Zong Shao-hui, Zhang Zhi-yong, Fu Song-wen, Li Ke-ke, Fang Ye, Lu Li, Xiao De-Qiang
1 College of Public Hygiene of Guangxi Medical University , Nanning, Guangxi, P.R. China .
2 Department of Osteopathia, the First Affiliated Hospital of Guangxi Medical University , Nanning, Guangxi, P.R. China .
Rejuvenation Res. 2015 Oct;18(5):413-21. doi: 10.1089/rej.2014.1657. Epub 2015 Aug 20.
Our previous study suggests that ginger root extract can reverse behavioral dysfunction and prevent Alzheimer's disease (AD)-like symptoms induced by the amyloid-β protein (Aβ) in a rat model. 6-Gingerol is the major gingerol in ginger rhizomes, but its effect on the treatment of AD remains unclear. In this study, we aimed to determine if 6-gingerol had a protective effect on Aβ1-42-induced damage and apoptotic death in rat pheochromocytoma cells (PC12 cells) and to investigate the underlying mechanisms by which 6-gingerol may exert its neuroprotective effects. Our results indicated that pre-treatment with 6-gingerol significantly increased cell viability and reduced cell apoptosis in Aβ1-42-treated cells. Moreover, 6-gingerol pretreatment markedly reduced the level of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA), the production of nitric oxide (NO), and the leakage of lactate dehydrogenase (LDH) and increased superoxide dismutase (SOD) activity compared with the Aβ1-42 treatment group. In addition, 6-gingerol pretreatment also significantly enhanced the protein levels of phosphorylated Akt (p-Akt) and glycogen synthase kinase-3β (p-GSK-3β). Overall, these results indicate that 6-gingerol exhibited protective effects on apoptosis induced by Aβ1-42 in cultured PC12 cells by reducing oxidative stress and inflammatory responses, suppressing the activation of GSK-3β and enhancing the activation of Akt, thereby exerting neuroprotective effects. Therefore, 6-gingerol may be useful in the prevention and/or treatment of AD.
我们之前的研究表明，生姜提取物可以逆转行为功能障碍，并预防大鼠模型中由淀粉样β蛋白（Aβ）诱导的阿尔茨海默病（AD）样症状。6-姜酚是姜根茎中的主要姜酚，但其对AD治疗的效果仍不清楚。在本研究中，我们旨在确定6-姜酚是否对Aβ1-42诱导的大鼠嗜铬细胞瘤细胞（PC12细胞）损伤和凋亡死亡具有保护作用，并研究6-姜酚发挥神经保护作用的潜在机制。我们的结果表明，用6-姜酚预处理可显著提高Aβ1-42处理细胞的活力并减少细胞凋亡。此外，与Aβ1-42处理组相比，6-姜酚预处理显著降低了细胞内活性氧（ROS）和丙二醛（MDA）水平、一氧化氮（NO）的产生以及乳酸脱氢酶（LDH）的泄漏，并提高了超氧化物歧化酶（SOD）活性。此外，6-姜酚预处理还显著提高了磷酸化Akt（p-Akt）和糖原合酶激酶-3β（p-GSK-3β）的蛋白水平。总体而言，这些结果表明，6-姜酚通过降低氧化应激和炎症反应、抑制GSK-3β的激活并增强Akt的激活，对培养的PC12细胞中Aβ1-42诱导的凋亡表现出保护作用，从而发挥神经保护作用。因此，6-姜酚可能对AD的预防和/或治疗有用。
