Evaluation of Natural Polyphenols for Anti-Aggregation and Potential Neuroprotection Against Beta-Amyloid, in Vitro

Alzheimer’s disease, a multifaceted neurodegenerative disorder, was the seventh leading cause of death at 5.8 million deaths in 2021 for all ages, with projections indicating a nearly threefold increase by 2060. The current treatment paradigm primarily involves behavioral management while attempting to alleviate symptoms, with limited focus on addressing the underlying pathogenesis: the formation and deposition of β- amyloid. Given the expected surge in Alzheimer’s disease cases in the coming decades, the quest for dietary and nutraceutical solutions as lifelong preventive measures becomes increasingly critical. This dissertation presents a comprehensive investigation into the neuroprotective potential of four prominent polyphenolic compounds: colominic acid, resveratrol, luteolin, and isosilybin. These compounds, found naturally in various plant sources, have drawn increasing attention for their potential to mitigate Alzheimer’s disease and its associated cognitive impairments. The evaluation scheme starts with a toxicity assessment of each compound, followed by an investigation into their interactions with Aβ monomer and oligomers, and finally categorization of their neuroprotective mechanisms. The findings were mainly quantified using MTT viability in
vitro assay and were validated with Congo Red and flow cytometry analysis. Moreover, the protocol developed herein provides a repeatable and comparable assessment for potential confounders to attenuate Aβ-induced toxicity of Alzheimer’s disease. These insights are vital for shaping future therapeutic strategies and prevention approaches, reinforcing the potential of natural compounds as a significant avenue in advancing our understanding and approach to Alzheimer’s disease.