title: 1,5-dicaffeoylquinic acid protects primary neurons from amyloid β 1-42-induced apoptosis via PI3K/Akt signaling pathway.
abstract: 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 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).
  
  
  RESULTS
  1,5-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.
  
  
  CONCLUSIONS
  These 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.
authors: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
authors: Hai-bing
authors: HB
authors: Xiao
authors: Xu
authors: X
authors: Cao
authors: Lei
authors: L
authors: Wang
authors: Xiao-qin
authors: XQ
authors: Run
authors: Ying
authors: Y
authors: Su
authors: Cheng
authors: C
authors: Tian
authors: Sheng-gang
authors: SG
authors: Sun
authors: Zhi-hou
authors: ZH
authors: Liang
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002934:Cinnamates / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D002934:Cinnamates; C100257:cynarine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt