1,5-Dicaffeoylquinic Acid Protects Primary Neurons From Amyloid Beta(1-42)-Induced Apoptosis Via Pi3k/Akt Signaling Pathway

Background Recently, 1,5-dicaffeoylquinic acid (1,5-DQA), a caffeoylquinic acid derivative isolated from Aster scaber, was found to have neuroprotective effects. However, the protective mechanisms of 1,5-DQA have not yet been clearly identified. The purpose of this study was to explore the protective mechanisms of 1,5-DQA on neuronal culture.Methods We investigated the neuroprotective effects of 1,5-DQA against amyloid beta(1-42) (A beta(42))-induced neurotoxicity in primary neuronal culture. To evaluate the neuroprotective effects of 1,5-DQA, primary cultured cortical neurons from neonate rats were pretreated with 1,5-DQA for 2 hours and then treated with 40 mu mol/L A beta(42) for 6 hours. Cell counting kit-8, Hoechst staining and Western blotting were used for detecting the protective mechanism. Comparisons between two groups were evaluated by independent t test, and multiple comparisons were analyzed by one-way analysis of variance (ANOVA).Results 1,5-DQA treated neurons showed increased neuronal cell viability against A beta(42) toxicity in a concentration-dependent manner, both phosphoinositide 3-kinase (PI3K)/Akt and extracellular regulated protein kinase 1/2 (Erk1/2) were activated by 1,5-DQA with stimulating their upstream tyrosine kinase A (Trk A). However, the neuroprotective effects of 1,5-DQA were blocked by LY294002, a PI3K inhibitor, but not by PD98059, an inhibitor of mitogen-activated protein kinase kinase. Furthermore, 1,5-DQA's anti-apoptotic potential was related to the enhanced inactivating phosphorylation of glycogen synthase kinase 3 beta (GSK3 beta) and the modulation of expression of apoptosis-related protein BcI-2/Bax.Conclusion These results suggest that 1,5-DQA prevents A beta(42)-induced neurotoxicity through the activation of PI3K/Akt followed by the stimulation of Trk A, then the inhibition of GSK3 beta as well as the modulation of BcI-2/Bax. Chin Med J 2011;124(17):2628-2635