*3.1. Cell Viability*

As shown in Figure 1, the cell viability of the Aβ group decreased to 62.6% compared to the C group (*p* < 0.05), suggesting that Aβ (25–35) is cytotoxic to SH-SY5Y cells in the present study. After pretreatment with equol (Eq + Aβ), the cell viability was significantly increased by 9.6% compared to the Aβ group, and the same effect was observed in the E2 group which exhibited increased cell viability of up to 12.9% compared to the Aβ group (*p* < 0.05). No cytotoxic effect on cells was found from the treatments of 17β-estradiol (E2) and S-equol (Eq). These findings indicate that Eq, like E2, had the potential to provide the neuroprotective effects against Aβ cytotoxicity *in vitro*. Moreover, in order to confirm that the neuroprotective effects of S-equol and 17β-estradiol against Aβ (25–35) cytotoxicity are mediated by the estrogen receptors, cells were pretreated with 1 μM ER antagonist ICI-182,780 for 1 h prior to Eq or E2 treatment. In the presence of Aβ (25–35), pretreatment with ER antagonism of ICI-182,780 prior to Eq or E2 treatments significantly abolished their effects on SH-SY5Y cell viability (*p* < 0.05). These results suggest that Eq and E2 antagonized the reduced cell viability-induced by Aβ (25–35), at least in part, by mediating the ERs.
