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