Cyanidin Ameliorates Bisphenol A-Induced Alzheimer's Disease Pathology by Restoring Wnt/β-Catenin Signaling Cascade: an In Vitro Study.

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 10µg/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 72h. A discernible and statistically significant difference was assessed in neurite extension at both doses at 72h, 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.