title: Ferulic acid alleviates Aβ25-35- and lipopolysaccharide-induced PC12 cellular damage: a potential role in Alzheimer's disease by PDE inhibition.
abstract: OBJECTIVE
  Phosphodiesterase (PDE) plays an important role in the pathogenesis of Alzheimer's disease (AD). Ferulic acid (FA) has a therapeutic benefit in the treatment of AD. We investigated whether this therapeutic effect is based on the modulation of the PDE/cyclic adenosine monophosphate (cAMP) pathway. In the present study, we investigated whether FA could abrogate Aβ25-35- and lipopolysaccharide-induced cellular damage.
  
  
  METHODS
  Cell viability, superoxide production, and the levels of inflammatory factors were investigated. We further investigated the intracellular levels of cAMP and Ca2+, both of which are associated with PDE activity. Furthermore, molecular docking was used to identify the binding mode between phosphodiesterase 4B2 (PDE4B2) and FA.
  
  
  RESULTS
  Pretreatment with FA significantly maintained cell viability, increased the levels of superoxide dismutase, and inhibited production of TNF-α and IL-1β induced by Aβ25-35. Moreover, pretreatment with FA increased the intracellular levels of cAMP and decreased the intracellular levels of Ca2+. The docking results also showed that FA has the potential to inhibit PDE4B2 activity.
  
  
  CONCLUSIONS
  Taken together, our results suggested that one of the therapeutic effects of FA on AD was potentially mediated by modulating the PDE/cAMP pathway.
authors: Hao
authors: H
authors: Huang
authors: Zeng-Chun
authors: ZC
authors: Ma
authors: Yu-Guang
authors: YG
authors: Wang
authors: Qian
authors: Q
authors: Hong
authors: Hong-Ling
authors: HL
authors: Tan
authors: Cheng-Rong
authors: CR
authors: Xiao
authors: Qian-De
authors: QD
authors: Liang
authors: Xiang-Lin
authors: XL
authors: Tang
authors: Yue
authors: Y
authors: Gao
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003373:Coumaric Acids / Q000494:pharmacology* / Q000627:therapeutic use; D000242:Cyclic AMP / Q000032:analysis; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000502:physiology; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides / Q000633:toxicity*; D062105:Molecular Docking Simulation; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D013482:Superoxide Dismutase / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D016229:Amyloid beta-Peptides; D003373:Coumaric Acids; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; C074636:amyloid beta-protein (25-35); C004999:ferulic acid; D000242:Cyclic AMP; D013482:Superoxide Dismutase; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C546993:PDE4B protein, rat; D002118:Calcium