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Abstract

We report for the first time that pterostilbene, a natural analog of resveratrol, shows anxiolytic-like action by downregulating phosphorylated levels of ERKs in the hippocampus of mice. Mice administered pterostilbene (1-10 mg/kg BW) by oral gavage were subjected to the Elevated-plus maze (EPM) test. Pterostilbene manifested anxiolytic activity at 1 and 2 mg/kg doses, demonstrated by an increase in percent permanence time and number of entries in open arms, critical determinants correlated with anxiety. This anxiolytic activity of pterostilbene was comparable to that of diazepam at 1 and 2 mg/kg in the EPM. The percent traveled distance and the percent permanence time in the enclosed arms were decreased with the 1 and 2 mg/kg doses. The 5 and 10 mg/kg doses did not show any anxiolytic effect. Locomotor activity was unaffected in 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; the 5 and 10 mg/kg doses showed no significant effect on the phosphorylation of ERKs. Pterostilbene was detected in serum and brain tissue following a single oral administration, demonstrating that the compound can cross the blood-brain barrier to reach the brain regions, including hippocampus, and thereby exert its anxiolytic effect. Resveratrol, the parent molecule of pterostilbene, did not have any anxiolytic effect.

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