Abstract: Objective To explore the effect of Ganoderma lucidum polysaccharides sulfate (GLPS) on learning and memory abilities of the mice with scopolamine-induced memory impairment and its mechanism.Methods Ganoderma lucidum polysaccharide (GLP) was modified by sulfation to obtain the GLPS.Fifty male Kunming mice were randomly divided into 5 groups:blank control,model control,positive control group (laci staw 100 mg/kg·d),GLP group (100 mg/kg·d),and GLPS group (100 mg/kg·d).The memory impairment mouse model was established with scopolamine.Learning ability of the mice was determined with step-down passive avoidance test.Acetylcholinesterase (AchE) was detected with kit method; the expression of nuclear factor-κB (NF-κB) p65 and cleaved caspase-3 in the hippocampus of the mice were measured with Western blot.Results Compared with those of the control group,the incubation period for jumping down from the platform was shortened and the number of error reaction decreased significantly for the model group.Compared with the model group,the GLP and GLPS showed significantly prolonged incubation period for jumping down from the platform and decreased number of error reaction (both P<0.05).The AChE activity of the model group (18.9±1.1 nmol/L) was obviously higher than that of the control group and the AChE activity of the GLP and GLPS group (17.1±0.8 and 15.0±0.6 nmol/L) decreased significantly compared with that of the model group (both P<0.05),with an obviously lower level in the GLPS group than that in the GLP group (P<0.05).Compared with those of the control group,the expressions of NF-κB p65 (0.83±0.04)and cleaved caspase-3 protein (0.55±0.04)in the hippocampus of the model group mice increased significantly (P<0.05); the expressions of NF-κB p65 (0.68±0.02)and cleaved caspase-3 protein (0.41±0.05)in the hippocampus of the GLPS group mice reduced significantly in comparison to those in the model mice (both P<0.05).Conclusion Ganoderma lucidum polysaccharides sulfate could significantly improve learning and memory ability of the mice with memory impairment and the mechanism of the effect may relate to the regulation of NF-kB signal transduction pathway.