Li Jing, Wang Pan, Hou Ming-Jie, Zhu Bao Ting
Shenzhen Key Laboratory of Steroid Drug Discovery and Development, School of Medicine The Chinese University of Hong Kong Shenzhen Guangdong China.
School of Life Sciences University of Science and Technology of China Hefei Anhui China.
MedComm (2020). 2023 Jun 19;4(4):e301. doi: 10.1002/mco2.301. eCollection 2023 Aug.
Alzheimer's disease (AD) is a common form of neurodegenerative disease in the elderly. Amyloid- (A)-associated neurotoxicity is an important component of the neurodegenerative change in AD. Recent studies have revealed a beneficial effect of anthocyanins in improving learning and memory in AD animal models. Using cultured HT22 mouse hippocampal neuronal cells as an in vitro model, we examined in this study the protective effect of ten pure components of anthocyanins against A -induced cytotoxicity and also investigated the mechanism of their protective effects. We found that treatment of HT22 cells with the pure components of anthocyanins dose-dependently rescued A -induced cytotoxicity, with slightly different potencies. Using petunidin as a representative compound, we found that it enhanced mitochondrial homeostasis and function in A -treated HT22 cells. Mechanistically, petunidin facilitated -catenin nuclear translocation and enhanced the interaction between -catenin and TCF7, which subsequently upregulated mitochondrial homeostasis-related protein Mfn2, thereby promoting restoration of mitochondrial homeostasis and function in A -treated HT22 cells. Together, these results reveal that the pure components of anthocyanins have a strong protective effect in HT22 cells against A -induced cytotoxicity by ameliorating mitochondrial homeostasis and function in a -catenin/TCF-dependent manner.
阿尔茨海默病（AD）是老年人常见的神经退行性疾病形式。淀粉样蛋白（A）相关的神经毒性是AD神经退行性改变的重要组成部分。最近的研究表明花青素在改善AD动物模型的学习和记忆方面具有有益作用。本研究以培养的HT22小鼠海马神经元细胞作为体外模型，检测了花青素的十种纯组分对A诱导的细胞毒性的保护作用，并探讨了其保护作用的机制。我们发现用花青素的纯组分处理HT22细胞可剂量依赖性地挽救A诱导的细胞毒性，但其效力略有不同。以矮牵牛素作为代表性化合物，我们发现它可增强A处理的HT22细胞中的线粒体稳态和功能。机制上，矮牵牛素促进β-连环蛋白核转位并增强β-连环蛋白与TCF7之间的相互作用，随后上调线粒体稳态相关蛋白Mfn2，从而促进A处理的HT22细胞中线粒体稳态和功能的恢复。总之，这些结果表明花青素的纯组分通过以β-连环蛋白/ TCF依赖性方式改善线粒体稳态和功能，在HT22细胞中对A诱导的细胞毒性具有强大的保护作用。
