Abstract: Objective To study the effects of long-term icariin(ICA)treatment on cognitive function, pathological changes and neuroinflammation in APP/PS1 transgenic mice models with Alzheimers disease(AD), and to explore the possible mechanism. Methods The effects of ICA on learning, memory and spatial cognitive abilities of mice were examined with Morris water maze test. The effects of ICA on the deposition of β-amyloid protein(Aβ), activation of glial cells and generation of proinflammatory cytokines in the hippocampus of mice were detected with immunohistochemical staining. The expression changes of proteins related to NF-κB inflammatory signal response pathway were determined with Western blotting. Results (1) ICA reduced the escape latency(F_{4th day}=4.96, P=0.017; F_{5th day}=9.37, P=0.001)and increased the time in the target section(F=9.31, P=0.001). (2) ICA reduced the deposition of Aβ in the hippocampus of APP/PS1 mice(F_{Aβ area}=153.28, P<0.001; F_{Aβ IOD}=87.18, P<0.001). (3) ICA inhibited the expression of neurone maker GFAP and Iba-1(F_GFAP=370.16, P<0.001; F_Iba-1=32.11, P<0.001)and the generation of proinflammatory cytokine IL-1β(F=190.10, P<0.001). (4) ICA decreased the ratio of NF-κ B pathway protein p-p65/p65(F=338.77, P<0.001). Conclusion Long-term icariin treatment can improve the cognitive function of APP/PS1 mice by inhibiting the activation of glial cells, reducing the generation of proinflammatory cytokines and Aβ deposition in the hippocampus.

Key words: Alzheimers disease, Icariin, β-amyloid protein, APP/PS1 transgenic mice, Neuroinflammation