Rice bran supplement ameliorates chronic restraint stress-induced depression-like behaviors in mice

Abstract

Depression is emerging as a social and health-related issue worldwide. Rice bran possesses a variety of biological properties; however, its potential efficacy and molecular mechanisms in depression remain unclear. This study investigated the antidepressant effects of rice bran supplement (RBS) in a mouse model of chronic restraint stress (CRS)-induced depression. RBS was administered to mice subjected to CRS for 5 weeks. RBS improved depressive symptoms in CRS-exposed mice, as evidenced by increased sucrose preference and reduced immobility time. It reduced hypothalamic–pituitary–adrenal (HPA) axis-related hormones. Additionally, RBS downregulated the glucocorticoid receptor (GR) pathway and upregulated the ERK–CREB–BDNF pathway in the prefrontal cortex and hippocampus. Furthermore, RBS increased neurotransmitter levels and decreased monoamine oxidase levels in the brain. Molecular docking analysis indicated that γ-oryzanol (ORY) interacts with GR. Moreover, ORY inhibited GR activity in GR-transfected HEK293T cells. The effects of ORY were not significantly altered by treatment with GR antagonist mifepristone or GR siRNA, suggesting ORY functions as a GR antagonist. Additionally, ORY administration improved depressive behaviors in CRS-exposed mice and modulated the imbalance of HPA axis-related hormones in mice. Mechanisms of action in the RBS were partially attributed by ORY, a key component of RBS, suggesting that ORY contributes synergistically to the effect of RBS. Thus, RBS administration could be a promising therapeutic approach to treating CRS-induced depression.