Xu Chenlin, Xiao Zijian, Wu Heng, Zhou Guijuan, He Duanqun, Chang Yunqian, Li Yihui, Wang Gang, Xie Ming
The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, People's Republic of China.
Xiangxi Autonomous Prefecture People's Hospital, Jishou, Hunan 416000, People's Republic of China.
Transl Neurosci. 2020 Sep 9;11(1):319-327. doi: 10.1515/tnsci-2020-0140. eCollection 2020.
Alzheimer's disease (AD) is a common neurodegenerative disorder without any satisfactory therapeutic approaches. AD is mainly characterized by the deposition of β-amyloid protein (Aβ) and extensive neuronal cell death. Curcumin, with anti-oxidative stress (OS) and cell apoptosis properties, plays essential roles in AD. However, whether bisdemethoxycurcumin (BDMC), a derivative of curcumin, can exert a neuroprotective effect in AD remains to be elucidated.
In this study, SK-N-SH cells were used to establish an model to investigate the effects of BDMC on the Aβ-induced neurotoxicity. SK-N-SH cells were pretreated with BDMC and with or without compound C and EX527 for 30 min after co-incubation with rotenone for 24 h. Subsequently, western blotting, cell viability assay and SOD and GSH activity measurement were performed.
BDMC increased the cell survival, anti-OS ability, AMPK phosphorylation levels and SIRT1 in SK-N-SH cells treated with Aβ. However, after treatment with compound C, an AMPK inhibitor, and EX527, an SIRT1inhibitor, the neuroprotective roles of BDMC on SK-N-SH cells treated with Aβ were inhibited.
These results suggest that BDMC exerts a neuroprotective role on SK-N-SH cells via AMPK/SIRT1 signaling, laying the foundation for the application of BDMC in the treatment of neurodegenerative diseases related to AMPK/SIRT1 signaling.
阿尔茨海默病（AD）是一种常见的神经退行性疾病，目前尚无令人满意的治疗方法。AD的主要特征是β-淀粉样蛋白（Aβ）沉积和广泛的神经元细胞死亡。姜黄素具有抗氧化应激（OS）和细胞凋亡特性，在AD中发挥重要作用。然而，姜黄素的衍生物双去甲氧基姜黄素（BDMC）是否能在AD中发挥神经保护作用仍有待阐明。
在本研究中，使用SK-N-SH细胞建立模型，以研究BDMC对Aβ诱导的神经毒性的影响。SK-N-SH细胞先用BDMC预处理，在与鱼藤酮共孵育24小时后，再分别用或不用化合物C和EX527处理30分钟。随后，进行蛋白质免疫印迹、细胞活力测定以及超氧化物歧化酶（SOD）和谷胱甘肽（GSH）活性测量。
BDMC提高了用Aβ处理的SK-N-SH细胞的存活率、抗OS能力、AMPK磷酸化水平和SIRT1水平。然而，在用AMPK抑制剂化合物C和SIRT1抑制剂EX527处理后，BDMC对用Aβ处理的SK-N-SH细胞的神经保护作用受到抑制。
这些结果表明，BDMC通过AMPK/SIRT1信号通路对SK-N-SH细胞发挥神经保护作用，为BDMC在治疗与AMPK/SIRT1信号通路相关的神经退行性疾病中的应用奠定了基础。
