1,5-dicaffeoylquinic acid protects primary neurons from amyloid β 1-42-induced apoptosis via PI3K/Akt signaling pathway.
- Author:
Hai-bing XIAO
1
;
Xu CAO
;
Lei WANG
;
Xiao-qin RUN
;
Ying SU
;
Cheng TIAN
;
Sheng-gang SUN
;
Zhi-hou LIANG
Author Information
- Publication Type:Journal Article
- MeSH: Amyloid beta-Peptides; pharmacology; Animals; Apoptosis; drug effects; Blotting, Western; Cell Survival; drug effects; Cells, Cultured; Cinnamates; pharmacology; Neurons; cytology; drug effects; metabolism; Phosphatidylinositol 3-Kinases; metabolism; Proto-Oncogene Proteins c-akt; metabolism; Rats; Rats, Sprague-Dawley; Signal Transduction; drug effects
- From: Chinese Medical Journal 2011;124(17):2628-2635
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDRecently, 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.
METHODSWe investigated the neuroprotective effects of 1,5-DQA against amyloid β(1-42) (Aβ(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 µmol/L Aβ(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).
RESULTS1,5-DQA treated neurons showed increased neuronal cell viability against Aβ(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 3β (GSK3β) and the modulation of expression of apoptosis-related protein Bcl-2/Bax.
CONCLUSIONThese results suggest that 1,5-DQA prevents Aβ(42)-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.