PSE (10, 20, and 40 μg/mL) attenuated the ↑ in inflammatory factors (NO and TNF-α), translocation of NF-κB, and phenotypic transformations in a dose-dependent manner. These inhibitory effects of PSE on microglia were supported by its regulatory effects on the CX3CR1/Nrf2 pathway. PSE (100 mg/kg) ↓ sickness, anxiety, and DLB in mice subjected to CRS and improved behav test performance. This evidence concerns the gene NFE2L2 and Lewy body dementia.