摘要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 β1-42 (Aβ42)-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 μmol/L Aβ42 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 Aβ42 toxicity in a concentration-dependent manner,both phosphoinositide 3-kinase (P13K)/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 3β (GSK3β) and the modulation of expression of apoptosis-related protein Bcl-2/Bax.Conclusion These results suggest that 1,5-DQA prevents Aβ42-induced neurotoxicity through the activation of PI3K/Akt followed by the stimulation of Trk A,then the inhibition of GSK3β as well as the modulation of Bcl-2/Bax.