Sulforaphane mitigates LPS-induced neuroinflammation through modulation of Cezanne/NF-κB signalling.

AIM

Neuroinflammation is a potent pathological process of various neurodegenerative diseases. Sulforaphane (SFN) is a natural product and acts as a neuroprotective agent to suppress inflammatory response in brain. The present study investigated the protective effect of Sulforaphane (SFN) on lipopolysaccharide (LPS)-induced neuroinflammation.

MATERIALS AND METHODS

Rats were divided into three groups: control group, LPS group and LPS + SFN group. Morris water maze test was carried out to evaluate the spatial memory and learning function of rats. The inflammatory cytokines levels in hippocampal tissues, plasma were measured by ELISA. The western blot was used to detect Cezanne/NF-κB signalling. For in vitro study, the Cezanne siRNA and scrambled control were transfected into BV2 cells, and then treated with or without 20 μM SFN before exposed to LPS. The inflammatory cytokines levels and Cezanne/NF-κB signalling were detected by ELISA and western blot, respectively. Co-IP assay were applied to investigate the regulation of Cezanne on ubiquitination of TRAF6 and RIP1.

KEY FINDINGS

SFN improved LPS-induced neurocognitive dysfunction in rats. It inhibited the neuroinflammation and activation of NF-κB pathway induced by LPS. The modulation of TRAF6 and RIP1 ubiquitination by Cezanne was playing a pivotal role in relation to the mechanism of SFN inhibiting NF-κB pathway.

SIGNIFICANCE

The results of our study demonstrated that SFN could attenuate LPS-induced neuroinflammation through the modulation of Cezanne/NF-κB signalling.