Salvianolic Acids Alleviate Chronic Mild Stress-Induced Depressive-Like Behaviors in Rats.

Background: Salvianolic acids possess anti-inflammatory properties. This study investigated the therapeutic effect of salvianolic acids on chronic mild stress (CMS)-induced depressive-like behaviors in rats and the involvement of toll-like receptor 4 () and myeloid differentiation factor 88 ().

Methods: Eighty male Sprague-Dawley rats were randomly subjected to CMS or non-CMS protocol for 6 weeks. Starting 3 weeks after CMS exposure, the rats in each group were administered saline, fluoxetine (positive control), salvianolic acids, or salvianolic acids + fluoxetine daily for 3 weeks. The body weight change, sucrose preference, and immobility duration in forced swimming were examined before and after drug treatment. The rats were sacrificed at 3 weeks after drug treatment. Quantitative real-time PCR was performed to measure the mRNA levels of and in the prefrontal cortex and hippocampus of rats.

Results: Compared with non-CMS rats, CMS rats had significantly reduced weight gains and sucrose preference, along with significantly increased immobility durations and elevated mRNA levels of and in both the prefrontal cortex and hippocampus. Treatment with fluoxetine and salvianolic acids, alone or in combination, facilitated weight gains, alleviated depressive-like behaviors, and reduced cerebral mRNA levels in CMS rats. Besides, fluoxetine and salvianolic acids additively suppressed mRNA expression in the prefrontal cortex of rats. Furthermore, mRNA levels in both hippocampus and prefrontal cortex positively correlated with mRNA expression, inflammatory cytokine secretion, and immobility duration but negatively correlated with sucrose preference.

Conclusions: Thus, salvianolic acids alleviate depressive-like behaviors, possibly by suppressing -mediated inflammatory signaling in the brain.