Protection of Neuronal Cells from Lipopolysaccharide-Induced Systemic Inflammation by Gossypetin

Abstract

Systemic inflammation caused by infection, surgery, or injury can lead to cognitive decline. Lipopolysaccharides are known as toll-like receptor 4 ligands, which are common to the cell walls of gram-negative bacteria. Activation of toll-like receptor 4 leads to the production of proinflammatory cytokines that subsequently mediate systemic inflammation. Furthermore, induc¬tion of systemic inflammation by lipopolysaccharide injection in mice can affect the brain, including cognitive functions. To investigate the neuroprotective role of gossypetin in systemic inflammation, a mouse hippocampal cell line (HT22) and mice were challenged with lipopolysaccharide. The increase in proinflammatory cytokines and reactive oxygen species caused by lipopolysaccharide treatment in HT22 cells was decreased by gossypetin treatment. To evaluate the protective function against memory impairment, gossypetin was orally administered to C57BL/6J mice receiving lipopolysaccharide injec¬tion. Lipopolysaccharide-induced memory deficit was observed in lipopolysaccharide-only treated group in Y-maze test. However, the group treated with gossypetin and lipopolysaccharide had a diminution in cognitive impairment. Consistent with the behavioral test results, the proinflammatory cytokines were also relatively downregulated in the gossypetin-treated mouse group. To sum up, gossypetin can be protect the neuron cells from inflammation in vitro and prevent the cognitive impairment in mice in vivo.