Ferulic Acid Improves Depressive-Like Behavior in Prenatally-Stressed Offspring Rats via Anti-Inflammatory Activity and HPA Axis.

Prenatal stress (PS) can increase the risk of nervous, endocrine and metabolic diseases, and immune dysfunction. Ferulic acid (FA) is a dietary phenolic acid that has pharmacological properties, including potent anti-inflammatory action. We used male, prenatally-stressed offspring rats to investigate the anti-depressive-like effects and possible anti-inflammatory mechanism of FA. We determined the animal behaviors, and the mRNA expression and concentration of inflammatory cytokines, and HPA axis. In addition, we assessed the modulation of hippocampal nuclear factor-κB (NF-κB) activation, neuronal nitric oxide synthase (nNOS) and glucocorticoid receptors (GR) expression via western blotting and immunohistochemistry. Administration of FA (12.5, 25, and 50 mg/kg/day, i.g.) for 28 days markedly increased sucrose intake, and decreased immobility time and total number of crossings, center crossings, rearing, and grooming in the male PS offspring. FA significantly reduced IL-6, IL-1β, and TNF-α concentration and increased IL-10 concentration in male, prenatally-stressed offspring, stimulated by the NF-κB pathway. In addition, FA inhibited interleukin-6 (), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), and increased mRNA and protein expression. Furthermore, FA markedly decreased the serum adrenocorticotropin (ACTH) and corticosterone concentration by the increase of GR protein expression. Taken together, this study revealed that FA has anti-depressive-like effects in male, prenatally-stressed offspring, partially due to its anti-inflammatory activity and hypothalamic-pituitary-adrenal (HPA) axis.