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 Aβ-induced neurotoxicity in neuronally differentiated PC12 cells. Differentiated PC12 cells were pretreated with 5， 10 or 20 μM AA before treatment with 20 μM Aβ. 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 v... More
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 Aβ-induced neurotoxicity in neuronally differentiated PC12 cells. Differentiated PC12 cells were pretreated with 5， 10 or 20 μM AA before treatment with 20 μM Aβ. 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 Aβ. 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 Aβ-treated differentiated PC12 cells. Moreover， LY294002， a specific PI3K inhibitor， was found to abolish the beneficial effects of AA on Aβ-induced apoptosis and tau protein hyperphosphorylation. Our findings demonstrated that AA protects differentiated PC12 cells from Aβ-induced apoptosis and tau protein hyperphosphorylation， which might be partially mediated by the activation of the PI3K/Akt/GSK-3β signaling pathway.
