Hyperforin attenuates aluminum-induced Aβ production and Tau phosphorylation via regulating Akt/GSK-3β signaling pathway in PC12 cells

Aluminum (Al) is a neurotoxicant and cause beta-amyloid (A beta) peptides aggregation and tau hyperphosphorylation. Hyperforin (HF) is one of the major active constituents of the extracts of St. John's Wort (Hypericum perforatum), can treat Alzheimer's disease (AD) and other diseases involving peptide accumulation and cognition impairment. To determine the effects of HF on Al-induced A beta formation and tau hyperphosphorylation, PC12 cells were cultured and treated with Al-malt (500 mu M) and/or HF (1 mu M). The results showed that HF treatment significantly attenuated Al-malt-induced A beta 1-42 production by reducing the expressions of APP, BACE1 and PS1, while increasing the expressions of sAPPa, ADAM9/10/17, and tau phosphorylation in PC12 cells. In addition, HF treatment also increased phosphorylation of AKT (Ser473) and inhibited GSK-3 beta activity by increasing phosphorylation of GSK-3 beta (Ser9). These results indicated that HF may exert the protection via regulating the AKT/GSK-3 beta signaling to reduce A beta production and tau phosphorylation in PC12 cells. Furthermore, these results could lead a possible therapeutics for the management of Al neurotoxicity.