Asiatic acid protects differentiated PC12 cells from Aβ 25-35 -induced apoptosis and tau hyperphosphorylation via regulating PI3K/Akt/GSK-3β signaling.

Amyloid β (Aβ) peptide can cause neurotoxicity in Alzheimer's disease (AD). The main purpose of the present study is to investigate the protective role of asiatic acid (AA) against Aβ25-35 -induced neurotoxicity in neuronally differentiated PC12 cells. Differentiated PC12 cells were pretreated with 5, 10 or 20 μM AA before treatment with 20 μM Aβ25-35 . The viability and apoptosis of differentiated PC12 cells were determined by MTT assay and Annexin V-FITC/PI double staining, respectively. The mitochondrial membrane potential (MMP) of differentiated PC12 cells was analyzed by JC-1 staining. The expression levels of proteins were detected by western blot analysis. We found that AA significantly increased the viability of differentiated PC12 cells but attenuated the mitochondria-mediated apoptosis dose-dependently when challenging with Aβ25-35 . Besides, the results of western blot analysis showed that AA prevented IκBα degradation and p65 nuclear translocation, and promoted the phosphorylation of Akt and GSK-3β in Aβ25-35 -treated differentiated PC12 cells. Moreover, LY294002, a specific PI3K inhibitor, was found to abolish the beneficial effects of AA on Aβ25-35 -induced apoptosis and tau protein hyperphosphorylation. Our findings demonstrated that AA protects differentiated PC12 cells from Aβ25-35 -induced apoptosis and tau protein hyperphosphorylation, which might be partially mediated by the activation of the PI3K/Akt/GSK-3β signaling pathway.