Anxiolytic action of pterostilbene: involvement of hippocampal ERK phosphorylation

Planta Med. 2013 Jun;79(9):723-30. doi: 10.1055/s-0032-1328553. Epub 2013 May 15.


Pterostilbene, a natural analog of resveratrol, has diverse health-beneficial properties. However, the neurological activities of this compound are largely unexplored. Here, we report that pterostilbene shows anxiolytic-like actions by down-regulating phosphorylated levels of extracellular regulated kinases in the hippocampus of mice. Adult male mice administered pterostilbene (1-10 mg/kg, p. o.) were subjected to the elevated plus maze test. Pterostilbene manifested anxiolytic activity at 1 and 2 mg/kg doses, demonstrated by increases in % permanence time and number of open arm entries. The locomotor activity of the animals was unaffected at all doses. Western blot analysis revealed a decrease in both extracellular regulated kinase 1 and extracellular regulated kinase 2 phosphorylation in hippocampal homogenates from mice treated with 1 and 2 mg/kg pterostilbene. Moreover, pterostilbene was detected in the plasma and brains of mice following single oral administration. Anxiolytic activity was not observed at the higher doses (5 and 10 mg/kg). However, no impairment of motor function was observed either, suggesting a favorable safety index for the compound. These results suggest that pterostilbene has the potential for therapeutic drug development for anxiety disorders.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Anxiety Agents / administration & dosage
  • Anti-Anxiety Agents / blood
  • Anti-Anxiety Agents / pharmacology*
  • Brain / drug effects
  • Brain / metabolism
  • Dose-Response Relationship, Drug
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Male
  • Mice
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Motor Activity / drug effects
  • Phosphorylation / drug effects
  • Stilbenes / administration & dosage
  • Stilbenes / blood
  • Stilbenes / pharmacology*


  • Anti-Anxiety Agents
  • Stilbenes
  • pterostilbene
  • Mitogen-Activated Protein Kinase 3