RESUMEN
In this study we compared the effects of a diverse set of natural polyphenolics ligands on in silico interactive modelling, in vitro anti-aggregative properties and neuronal toxicity of ß amyloid. The ß amyloid-binding characteristics of optimised structural conformations of polyphenols with ascribed neuroprotective actions including punicalagin, myricetin, luteolin and honokiol were determined in silico. Thioflavin T and transmission electron microscopy were used to assess in vitro inhibitory effects of these polyphenols on Aß1-42 fibril and aggregation formation. Phaeochromocytoma (PC12) cells were exposed to Aß1-42, alone and in combination with test concentrations of each polyphenol (100 µM) and viability measured using MTT assay. Aß1-42 evoked a concentration-dependent loss of cell viability in PC12 cells, in which all four polyphenols demonstrated significant inhibition of neurotoxicity. While all compounds variably altered the morphology of Aß aggregation, the flavonoids luteolin and myricetin and the lignan honokiol all bound in a similar hydrophobic region of the amyloid pentamer and exerted the most pronounced inhibition of Aß1-42 aggregation. Each of the polyphenols demonstrated neuroprotective effects in PC12 cells exposed to Aß1-42, including punicalagin. These findings highlight some structure-activity insights that can be gleaned into the anti-aggregatory properties of bioactive polyphenols based on modelling of their binding to ß-amyloid, but also serve to highlight the more general cellular neuroprotective nature of such compounds.