Orientin improves depression‐like behavior and BDNF in chronic stressed mice

Scope Oxidative stress is involved in chronic stress‐induced depression and the disruption of neurotransmission and neuroplasticity. Recently, orientin, a phenolic compound abundant in some fruits, millet, and herbs, has been shown to have antioxidant properties. This study investigated the potential antidepressant effects of orientin against chronic stress and its underlying mechanisms. Methods and results The chronic unpredictable mild stress (CUMS) model was used to investigate the effects of orientin on behavior and biochemical alterations in mice. After 2 weeks of the CUMS protocol, the mice were treated with orientin (20 mg/kg and 40 mg/kg, oral gavage) for 3 weeks. Administration of orientin significantly alleviated the CUMS‐induced depression‐like behavior, including sucrose preference reduction, locomotor activity decline, and hypomotility. Orientin treatment attenuated the oxidative stress markers and increased the concentrations of serotonin and norepinephrine in the hippocampus and prefrontal cortex of CUMS mice. Orientin treatment also increased the brain‐derived neurotrophic factor and synapse‐associated proteins (synaptophysin and postsynaptic density protein 95) of CUMS mice. Conclusion Orientin exerts antidepressant‐like effects on CUMS mice, specifically by improving central oxidative stress, neurotransmission, and neuroplasticity. Therefore, supplementation with orientin‐enriched food or fruit could be beneficial as a preventive strategy for chronic stress‐induced depression.