Palmatine Attenuates LPS-Induced Activation of Human Microglia (HMC3) by Suppressing NF-κB Nuclear Translocation

Microglia are the main effector cells in neuroinflammation, and their chronic activation is a factor in the progressive development of neurological diseases. Evidence has shown that palmatine attenuates the proinflammatory response and reduces oxidative stress in murine microglia by suppressing NF-κB. However, its effect on NF-κB translocation and the production of reactive oxygen species (ROS) in human microglia has not been explored. Consequently, we evaluated the effect of palmatine on NF-κB nuclear translocation and superoxide anion (O2∙-) production in human microglia (HMC3) stimulated by lipopolysaccharide (LPS). Methods: The PyMOL visualization system, molecular docking, and the protein-ligand interaction profiler (PLIP) were used to analyze the affinity of palmatine for NF-κB (p50) and the possible putative binding site. Microglia were stimulated with LPS for 1 h in the absence or presence of palmatine at different concentrations. We quantified NF-κB translocation by immunofluorescence and O2∙- production using the nitroblue tetrazolium assay. Results: In silico analysis suggests that palmatine interacts stably with NF-κB through electrostatic and hydrophobic bonds. Consistently, in vitro studies revealed that palmatine significantly reduced NF-κB translocation after LPS stimulation. We observed that O2∙- production was significantly decreased under the same treatments. Conclusion: Palmatine has important capabilities to reduce NF-κB translocation and O2∙- levels, suggesting a potential regulatory effect on the proinflammatory response. Further research is required to elucidate the expression levels of pro-inflammatory cytokines and to explore the anti-inflammatory effect of palmatine in human microglia.