B355252 is a small molecular compound known for potentiating neural growth factor and protecting against neuronal cell death induced by glutamate in vitro and cerebral ischemia in vivo. However, its other biological functions remain unclear. This study aims to investigate whether B355252 suppresses neuroinflammatory responses and cell death in the brain. C57BL/6j mice were intraperitoneally injected with a single dosage of lipopolysaccharide (LPS, 1 mg/kg) to induce inflammation. B355252 (1 mg/kg) intervention was started two days prior to the LPS injection. The animal behavioral changes were assessed pre- and post-LPS injections. The animal brains were harvested at 4 and 24 h post-LPS injection, and histological, biochemical, and cytokine array outcomes were examined. Results showed that B355252 improved LPS-induced behavioral deterioration, mitigated brain tissue damage, and suppressed the activation of microglial and astrocytes. Furthermore, B355252 reduced the protein levels of key pyroptotic markers TLR4, NLRP3, and caspase-1 and inhibited the LPS-induced increases in IL-1β, IL-18, and cytokines. In conclusion, B355252 demonstrates a potent anti-neuroinflammatory effect in vivo, suggesting that its potential therapeutic value warrants further investigation.
Keywords:B355252; NLRP3; astrocyte; brain; cytokine; lipopolysaccharide; microglia; neuroinflammation; pyroptosis.