Sophocarpine prevents LPS and IFN-γ-stimulated oxidative stress and neuroinflammation of BV-2 microglia by regulating the AMPK/NF-κB signaling pathway.

Microglia can be continuously activated to produce proinflammatory cytokines and reactive oxygen species, leading to progressive neurodegeneration. Sophocarpine (ScP) has been reported to exhibit neuroprotective and anti-inflammatory activities, but it remains unclear whether microglia are involved in these effects. BV-2 cells were exposed to ScP, AMP-activated protein kinase (AMPK) agonist AICAR, and the AMPK inhibitor Compound C for 30 min before being treated with lipopolysaccharide (LPS) and IFN-γ for 24 h. The levels of oxidative response and inflammation were detected by kits, immunofluorescence, ELISA, and western blotting. The AMPK/NF-κB expression was measured using western blotting. In vivo effects were next verified using LPS-induced neuroinflammatory mouse models. Overall, 1, 2, and 4 μM ScP had no effects on BV-2 cells. After BV-2 cells were stimulated with LPS and IFN-γ, the levels of antioxidant enzymes were decreased, whereas the levels of allograft inflammatory factor 1 (Iba-1) and inflammatory mediators were increased. After LPS and IFN-γ stimulation, the levels of phosphorylated (p)-AMPK protein were decreased, whilst the levels of p-IκBα and p-p65 protein were increased. ScP then reduced the levels of Iba-1, inflammatory mediators, p-IκBα, and p-p65 proteins, whilst increasing the levels of antioxidant enzymes and p-AMPK. ScP treatment reduced the extent of neuronal damage in mice, significantly improving inflammation and oxidative stress damage. The antioxidant and anti-inflammatory effects of ScP were found to be enhanced after AICAR intervention. ScP can inhibit LPS and IFN-γ-stimulated oxidative response and neuroinflammation in BV-2 cells through the AMPK/NF-κB axis.