Effects of naturally occurring compounds on fibril formation and oxidative stress of β-amyloid

beta-Amyloid (beta A)-induced oxidative toxicity on neuronal cells is a principal route in Alzheimer's disease (AD), and its toxicity occurs after fibril formation. Inhibitory or promoting effects of naturally occurring compounds on beta A fibril formation were evaluated. Among 214 tested compounds, curcuminoids, flavone type flavonoids, and naphthoquinones were shown to be potent inhibitors of beta A fibrilization. The addition of the curcuminoids, curcumin, demethoxycurcumin, and bisdemethoxycurcumin strongly inhibited beta A fibril formation. Flavonoids such as quercetin, rhamnetin, and fisetin strongly inhibited A fibril formation. Limonoids, cinnamic acids, and catechins enhanced fibril formation in vitro. Anthothecol possessed the most enhancing activity on fibril formation of the compounds tested. On the other hand, it was found that curcuminoids showed cytotoxicity with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay and did not protect HT22 murine neuroblastoma cells from beta A(25-35) insult. Two flavone type flavonoids, morin and quercetin, exhibited no cytotoxicity and strongly protected HT22 murine neuroblastoma cells from PA(25-35) oxidative attack. Conclusively, morin or quercetin could be a key molecule for the development of therapeutics for AD.