Gamma-Oryzanol Solid Dispersion Attenuates Dexamethasone-Induced Depressive-like Behaviors in Rats Associated with Calbindin-1 and Calcium Signaling

Depression is associated with dysfunction of the hypothalamic–pituitary–adrenal axis, neurotransmitter imbalance, and calcium signaling deficits. Although gamma-oryzanol (GO) has shown antidepressant effects, its underlying molecular mechanism remains elusive, while its poor aqueous solubility limits its nutraceutical application. To overcome this obstacle, we successfully developed GO solid dispersion (GOSD) with enhanced water solubility for nutraceutical formulations. This study examined the antidepressant effect of GOSD in dexamethasone (Dx)-induced depressive-like behaviors in rats using behavioral tests, including the sucrose preference test and forced-swimming test (FST). The Dx group showed a reduction in sucrose consumption and mobility time in the FST compared with controls, both of which improved following GOSD administration. Proteomics revealed changes associated with the calcium signaling pathway. Calbindin (Calb1) expression was reduced in the Dx group, whereas GOSD administration restored Calb1 levels. Given the role of Calb1, a calcium-binding protein (CBP) involved in intracellular calcium buffering, reduced Calb1 expression in the Dx group may contribute to calcium signaling dysregulation. In contrast, GOSD can attenuate Calb1 levels, which potentially contribute to its antidepressant effects. These findings suggest that the antidepressant-like effects of GOSD may involve modulation of calcium homeostasis, supporting its potential as a complementary intervention for Dx-induced depressive-like behaviors.