LAUSR

Neuroinflammation is a critical factor in the onset and progression of various brain disorders. Upon exposure to inflammatory stimuli, glial cells become activated, releasing excessive proinflammatory mediators that exacerbate neuropathological conditions. Nitric oxide contributes to neuroinflammation, neurotoxicity, and neuronal death, making its regulation in activated glial cells essential for treating neuroinflammation. Lespedeza bicolor, a traditional medicine used for fever, cough, and nephritis treatment, has a neuroprotective effect attributed to the pterocarpan 1-methoxylespeflorin G11 (MLG), as identified in our previous study. This study examines the protective role of MLG in lipopolysaccharide (LPS)-stimulated glial cells. We found that MLG treatment attenuated LPS-induced nitrite release by downregulating inducible nitric oxide synthase expression in astrocytes. Additionally, MLG impeded LPS-induced nuclear translocation of the p65 subunit of nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-κB) and decreased LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK). The MLG demonstrated similar inhibitory effects on nitrite release and p65 nuclear translocation in microglial cells. Molecular docking analyses unveiled the potential binding mode of MLG to ERK. Collectively, our results indicate that MLG may possess therapeutic potential in treating neuroinflammatory diseases by suppressing nitrite release in glial cells.