Poria cocos Polysaccharides Regulate Anxiety and Depression-like Behaviors Induced by Lipopolysaccharide through NF-κB and NLRP3 Signaling Pathways

Abstract

Objective: To explore the effect of Poria cocos polysaccharides (Poria cocos polysaccharide, PPS) on anxiety and depression-like behaviors induced by lipopolysaccharide (LPS) and analyze its mechanism. Methods: BV-2 cells were divided into control group, LPS group, LPS+fluoxetine group and LPS+PPS (PPS of 4, 8, 16 μmol/L, respectively). After 24 h treatment, the level of intracellular reactive oxygen species (ROS) was detected by dichlorodihydrofluorescein dihydroacetate (DCFH-DA) fluorescence probe, the level of NO in culture supernatant was detected by griess method, and the levels of TNF-α and IL-1β in cell supernatant were detected by enzyme linked immunosorbent assay (ELISA). The levels of CD206, CD16/32 and NF-κB p65 were detected by western blot. In animal experiment, mice were divided into control group, model group, LPS+fluoxetine group, LPS+PPS low dose group (20 mg/kg) and LPS+PPS high dose group (80 mg/kg). Depression-like behavior test was performed, and the concentration of TNF-α, IL-1β and IL-18 in hippocampus was detected. The protein levels of CD206, CD16/32, NF-κB p65, NLRP3, ASC and Cleaved caspase-1 in hippocampus were analyzed. Results: Compared with LPS group, 4,8,16 μmol/L PPS significantly decreased the relative fluorescence intensity of ROS (P<0.01), decreased the levels of NO, TNF-α and IL-1β (P<0.01), decreased the levels of CD16/32 and NF-κB p65 (P<0.05), and increased the level of CD206 (P<0.05). Compared with the model group, the preference rate, crossing times and modification times in LPS+PPS low dose group and high dose LPS+PPS group significantly increased (P<0.01), while the tail suspension time and forced swimming immobility time significantly decreased (P<0.01). Compared with the model group, the levels of IL-1β, IL-18 and TNF-α in LPS+PPS low dose group and LPS+PPS high dose group significantly decreased (P<0.01), CD16/32 and NF-κB p65 level were significantly down-regulated, CD206 was significantly up-regulated, and the levels of NLRP3, ASC and Cleaved caspase-1 significantly decreased. Conclusion: Poria cocos polysaccharide can alleviate LPS-induced anxiety and depression-like behavior by inhibiting NF-κB and NLRP3 signal pathways.

Keywords

• poria cocos polysaccharide
• nf-κb signal pathway
• nlrp3 signal pathway
• lipopolysaccharide
• anxiety
• depression-like behavior