The green tea polyphenol (−)-epigallocatechin-3-gallate inhibits amyloid-β evoked fibril formation and neuronal cell death in vitro

► Alzheimer’s protein amyloid-β and pro-oxidants elicit neurotoxicity in PC12 cells. ► We compared protective effects of bioactive polyphenols against these stressors. ► (−)-Epigallocatechin-3-gallate and grape skin extract protect against amyloid-β. ► (−)-Epigallocatechin-3-gallate directly inhibits amyloid-β aggregation. ► Bioactive amyloid-β aggregation inhibitors may confer a neuroprotective advantage. Alzheimer’s disease is associated with amyloid-β plaques eliciting neuronal oxidative stress. Many naturally occurring compounds have antioxidant properties, but it is unclear if this alone protects against amyloid-β exposure. This study investigated the protective effects of selected bioactive compounds against amyloid-β and pro-oxidant-evoked neurotoxicity in PC12 cells. Neither resveratrol, (−)-epigallocatechin-3-gallate, cyanidin rutinoside or grape skin extract protected PC12 cells against H2O2 or tert butyl hydroperoxide toxicity. Amyloid-β resulted in a concentration-dependent reduction in PC12 cell viability that was unaffected by resveratrol or cyanidin rutinoside pre-treatment. By contrast, (−)-epigallocatechin-3-gallate and grape skin extract significantly reduced amyloid-β-evoked neurotoxicity (by 40%). Only (−)-epigallocatechin-3-gallate was directly able to inhibit amyloid-β aggregate and fibril formation. These results suggest that (−)-epigallocatechin-3-gallate protects neuronal cells by disrupting amyloid-β fibril formation; bioactive polyphenols which disrupt fibril aggregation may confer additional neuroprotection when compared against antioxidant activity alone.