Pterostilbene Improves Stress-Related Behaviors and Partially Reverses Underlying Neuroinflammatory and Hormonal Changes in Stress-Challenged Mice

Pterostilbene is a natural compound contained in various dietary sources that has received tremendous attention due to its antioxidant properties with promising benefits in cancers and vascular diseases. Currently, little is known about pterostilbene-associated neuroimmune endocrine effects. We aimed to examine the efficacy of pterostilbene for improving stress-related behaviors, neuroinflammation, and hormonal changes in a mouse stress model. To evaluate the efficacy of oral administration of pterostilbene or vehicle for 16 days for improving behavior, inflammation, and hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, mice were divided into a normal control group or one of five restraint stress groups-the vehicle group; the 20, 40, or 80 mg/[kg·day] pterostilbene treatment group; or the 20 mg/[kg·day] resveratrol treatment group. Open field and forced swimming tests were conducted. Hippocampal brain-derived neurotrophic factor (BDNF) levels, endocrine hormone levels, oxidative stress parameters, and histopathological features were assessed. Oral pterostilbene administration significantly increased the measured times in the open field and forced swimming tests, elevated the BDNF levels, decreased the inducible nitric oxide synthase and superoxide dismutase levels in the brain, and reduced the plasma adrenocorticotropic hormone and corticosterone levels. Compared with vehicle treatment, pterostilbene dose dependently increased the numbers of neurons and decreased the numbers of glial and tumor necrosis factor alpha-immunolabeled cells in the hypothalamus. These findings suggest that pterostilbene may effectively modulate stress-related abnormal behaviors, neuroinflammation, and HPA axis hyperactivity.