Flavonoids possess neuroprotective effects on cultured pheochromocytoma PC12 cells: A comparison of different flavonoids in activating estrogenic effect and in preventing beta-amyloid-induced cell death

Despite the classical hormonal effect, estrogen possesses a neuroprotective effect in the brain, which has led many to search for novel treatments for neurodegenerative diseases. Flavonoids, a group of compounds mainly derived from vegetables, share a resemblance, chemically, to estrogen, and indeed, some have been used as estrogen substitutes. To search for potential therapeutic agents against neurodegenerative diseases, different subclasses of flavonoids were analyzed and compared with estrogen. First, the estrogenic activities of these flavonoids were determined by activating the estrogen-responsive elements in cultured MCF-7 breast cancer cells. Second, the neuroprotective effects of flavonoids were revealed by measuring its inhibition effects on the formation of reactive oxygen species, the aggregation of beta-amyloid, and the induction of cell death by beta-amyloid in cultured neuronal PC12 cells. Among these flavonoids, baicalein, scutellarin, hibifolin, and quercetin-3'-glucoside possessed the strongest effect in neuroprotection; however, the neuroprotective activity did not directly correlate with the estrogenic activity of the flavonoids. Identification of these flavonoids could be very useful in finding potential drugs, or food supplements, for treating Alzheimer's disease