Abstract：
Alzheimer\'s disease (AD) is a progressive neurodegenerative disorder causing memory loss and cognitive decline, linked to amyloid-beta (Aβ) plaques and hyperphosphorylated tau protein accumulation in the brain. Environmental pollutant bisphenol A (BPA) has been implicated in AD pathology due to its neurotoxic effects. This study aims to evaluate cyanidin from flower bracts of Musa acuminata Colla (red variety; AAA group) for its neuroprotective properties against BPA-induced AD pathology. The extraction of cyanidin was optimized using 70% ethanol in acidified water, showing promising anti-acetylcholinesterase activity. Cyanidin was effectively purified from the resultant extract and characterized using spectroscopic techniques. Two gradient doses of cyanidin (90 and 10 µg/ml) were determined based on cell viability assay. The role of cyanidin in promoting nerve growth and differentiation was assessed in PC12 cells for up to 72 h. A discernible and statistically significant difference was assessed in neurite extension at both doses at 72 h, followed by pre-treatment with cyanidin. BPA stimulation significantly increased the p-tau expression compared to the control (p < 0.0001). Pre-treatment with cyanidin reduced the tau expression; however, a significant difference was observed compared to control cells (p = 0.0003). Cyanidin significantly enhanced the mRNA expression of Wnt3a (p < 0.0001), β-catenin (p = 0.0004), and NeuroD1 (p = 0.0289), and decreased the expression of WIF1(p = 0.0040) and DKK1 (p < 0.0001), which are Wnt antagonist when compared to cells stimulated with BPA. Conclusively, our finding suggests that cyanidin could agonize nerve growth factor and promote neuronal differentiation, reduce tau-hyperphosphorylation by restoring the Wnt/β-catenin signaling cascade, and thereby render its neuroprotective potential against BPA-induced AD pathology.
摘要：
阿尔茨海默病(Alzheimer\'sdisease,AD)是一种进行性神经退行性疾病,引起记忆丧失和认知功能下降,与β淀粉样蛋白（Aβ）斑块和大脑中过度磷酸化的tau蛋白积累有关。环境污染物双酚A（BPA）由于其神经毒性作用而与AD病理有关。这项研究旨在评估来自MusaacuminataColla（红色品种；AAA组）的花苞中的花青素对BPA诱导的AD病理的神经保护特性。用70％乙醇在酸化水中优化花青素的提取，显示有希望的抗乙酰胆碱酯酶活性。从所得提取物中有效地纯化了花青素，并使用光谱技术进行了表征。基于细胞活力测定确定两种梯度剂量的花青素(90和10μg/ml)。在PC12细胞中长达72小时，评估了花青素在促进神经生长和分化中的作用。在72小时的两种剂量下，在神经突延伸方面评估了可辨别的且具有统计学意义的差异。然后用花青素预处理。与对照相比,BPA刺激显著增加p-tau表达(p<0.0001)。用花青素预处理降低了tau表达；然而，与对照细胞相比,观察到显著差异(p=0.0003).Cyanidin显著增强Wnt3a的mRNA表达(p<0.0001),β-连环蛋白（p=0.0004），和NeuroD1（p=0.0289），降低了WIF1(p=0.0040)和DKK1(p<0.0001)的表达,当与用BPA刺激的细胞相比时,其是Wnt拮抗剂。最后，我们的发现表明，花青素可以激动神经生长因子并促进神经元分化，通过恢复Wnt/β-catenin信号级联降低tau-过度磷酸化，从而赋予其针对BPA诱导的AD病理的神经保护潜力。
