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 no...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 IB1-42 （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 pmol/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 （PI3K）/Akt and extracellular regulated protein kinase 1/2 （Erkl/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 313 （GSK3β） and the modulation of expression of apoptosis-related protein Bcl-2/Bax. Conclusion These resutts suggest that 1,5-DQA prevents AI342-induced neurotoxicity through the activation of PI3K/Akt followed by the stimulation of Trk A, then the inhibition of GSK313 as well as the modulation of Bcl-2/Bax.展开更多
文摘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 IB1-42 （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 pmol/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 （PI3K）/Akt and extracellular regulated protein kinase 1/2 （Erkl/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 313 （GSK3β） and the modulation of expression of apoptosis-related protein Bcl-2/Bax. Conclusion These resutts suggest that 1,5-DQA prevents AI342-induced neurotoxicity through the activation of PI3K/Akt followed by the stimulation of Trk A, then the inhibition of GSK313 as well as the modulation of Bcl-2/Bax.
