Gallic acid induces neuronal cell death through activation of c-Jun N-terminal kinase and downregulation of Bcl-2

Ann N Y Acad Sci. 2009 Aug;1171:514-20. doi: 10.1111/j.1749-6632.2009.04728.x.


Oxidative stress induced by reactive oxygen species (ROS) is strongly associated with the pathogenesis of various neurodegenerative disorders, including Alzheimer's disease. We investigated the possible combined effects of gallic acid and resveratrol, which are major antioxidants present in fruit, including grapes, on PC12 rat pheochromocytoma (PC12) cell death. Gallic acid did not protect against H(2)O(2)-induced PC12 cell death; it reduced the viability of PC12 cells in a dose-dependent manner. Gallic acid also induced cleavage of poly (ADP-ribose) polymerase, which is strongly related to apoptosis in neurons. Gallic acid induced the phosphorylation of c-Jun N-terminal protein kinase (JNK) and the downregulation of Bcl-2 in PC12 cells. Treatment of PC12 cells with resveratrol increased their viability in a dose-dependent manner by blocking the activation of JNK and the downregulation of Bcl-2. Furthermore, gallic acid led to a progressive reduction in the viability of vector-transfected PC12 cells, which was delayed in PC12 cells that overexpressed Bcl-2. The JNK inhibitor SP600125 protected against gallic acid-induced PC12 cell death. Collectively, these findings suggest that the combined effects of dietary phenolic phytochemicals on oxidative neuronal cell death and antioxidants differ in ROS-mediated neuronal cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthracenes / pharmacology
  • Antioxidants / pharmacology
  • Apoptosis / drug effects*
  • Blotting, Western
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Enzyme Activation / drug effects
  • Gallic Acid / chemistry
  • Gallic Acid / pharmacology*
  • Hydrogen Peroxide / pharmacology
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Molecular Structure
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Oxidants / pharmacology
  • PC12 Cells
  • Phosphorylation / drug effects
  • Plasmids / genetics
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Rats
  • Resveratrol
  • Stilbenes / chemistry
  • Stilbenes / pharmacology
  • Transfection


  • Anthracenes
  • Antioxidants
  • Oxidants
  • Proto-Oncogene Proteins c-bcl-2
  • Stilbenes
  • pyrazolanthrone
  • Gallic Acid
  • Hydrogen Peroxide
  • Poly(ADP-ribose) Polymerases
  • JNK Mitogen-Activated Protein Kinases
  • Resveratrol