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Title: Anxiolytic action of pterostilbene: involvement of hippocampal ERK phosphorylation

Author
item RAHIM, AL - Johns Hopkins University School Of Medicine
item Rimando, Agnes
item SILISTREL, KALPTEN - Ministry Of Health
item EL-ALFY, ABIR - Chicago State University

Submitted to: Planta Medica
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/9/2013
Publication Date: 5/15/2013
Citation: Rahim, A., Rimando, A.M., Silistrel, K., El-Alfy, A.T. 2013. Anxiolytic action of pterostilbene: involvement of hippocampal ERK phosphorylation. Planta Medica. 19:723-730.

Interpretive Summary: 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 antianxiety action by interfering with the activity of enzymes involved in the pathway that causes anxiety. Mice fed pterostilbene manifested anti-anxiety behavior in the elevated-plus maze test, a behavioral model for assessing anxiety. In addition, the antianxiety activity of pterostilbene was comparable to that of the clinically-used drug, diazepam. The locomotor activity of the animals was unaffected. Moreover, pterostilbene was detected in the serum and brain of mice. These results suggest that pterostilbene has the potential to become a candidate compound for therapeutic drug development for anxiety disorders.

Technical Abstract: 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 action by downregulating phosphorylated levels of ERKs in the hippocampus of mice. Adult male mice administered pterostilbene (1-10 mg/kg BW, po) were subjected to elevated-plus maze (EPM) test. Pterostilbene manifested anxiolytic activity at 1 and 2 mg/kg doses, demonstrated by increase in % permanence time and number of open arm entries. In addition, the anxiolytic activity of pterostilbene was comparable to that of diazepam at 1 and 2 mg/kg in the EPM. The locomotor activity of the animals was unaffected at all doses. Western blot analysis corroborated the observed behaviors in the EPM, revealing a decrease in both ERK1 and ERK2 phosphorylation in hippocampal homogenates from mice treated with 1 and 2 mg/kg doses. Moreover, pterostilbene was detected in the serum and brain of mice following single oral administration. Neither anxiolytic nor motor activity impairment was observed at the higher doses (5 and 10 mg/kg), suggesting the favorable safety index of the compound. These results suggest that pterostilbene has the potential to become a candidate compound for therapeutic drug development for anxiety disorders.