Proanthocyanidin prevents lipopolysaccharide-induced depressive-like behavior in mice via neuroinflammatory pathway

Recent studies have demonstrated neuroinflammation and increased cytokine levels are associated with depression. Aware of the efficacy the potential anti-inflammatory and antioxidative activity of proanthocyanidin, the present study was designed to investigate the effects of proanthocyanidin on lipopolysaccharide (LPS)-induced depressive-like behavior in mice. In depressive behavior tests, the immobility time of forced swimming test (FST) and tail suspension test (TST) was increased when mice were administrated a single dose of LPS (0.83 mg/kg, i.p.), whereas these alterations were reversed by proanthocyanidin treatment (80 mg/kg, p.o.). In anxiety behavior tests, all the anxiety-related parameters, such as number of buried marble, time spent in the open arm and close arm did not show statistical differences between LPS and control groups. However, anxiolytic effects were observed in marble-burying test and elevated plus maze test in single proanthocyanidin treatment and proanthocyanidin treatment together with LPS group. Further assays indicated that LPS-induced overexpression of pro-inflammatory cytokines in the hippocampus, prefrontal cortex (PFC) and amygdala were reversed by proanthocyanidin treatment. Furthermore, proanthocyanidin inhibited the LPS-induced iNOS and COX-2 overexpression, via the modulation of NF-κB in the hippocampus, PFC and amygdala. Taken together, proanthocyanidin may be an effective therapeutic agent for LPS-induced depressive-like behaviors via its potent anti-inflammatory property.