Scutellarin protects against lipopolysaccharide-induced behavioral deficits by inhibiting neuroinflammation and microglia activation in rats

Depression is a complex and heterogeneous mental disorder. Yet, the mechanisms behind depression remain elusive. Increasing evidence suggests that inflammatory reaction and microglia activation are involved in the pathogenesis of depression. Scutellarin has been found to have anti-inflammatory and antioxidant effects in various diseases. The aim of the present study was to investigate the anti-depressant effects and potential mechanism of scutellarin in the lipopolysaccharide (LPS)-induced depression animal model. The behavioral tests showed that scutellarin administration ameliorated LPS-induced depressive-like behaviors. Additionally, the scutellarin treatment inhibited reactive oxygen species (ROS) generation. Western blot analysis results showed that scutellarin pretreatment suppressed LPS-induced the protein levels of NLRP3, caspase-1, and IL-1β. Furthermore, immunostaining results showed that scutellarin pretreatment inhibited LPS-induced microglia activation in the hippocampus of rats. These findings suggest that scutellarin effectively improves LPS-induced inflammation-related depressive-like behaviors by inhibiting LPS-induced neuroinflammation and microglia activation, possibly via regulation of the ROS/NLRP3 signaling pathway and microglia activation. Thus, scutellarin may serve as a potential therapeutic strategy for depression.